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- Creators: Arizona State University
Description
Engineered nanoparticles (NP; 10-9 m) have found use in a variety of consumer goods and medical devices because of the unique changes in material properties that occur when synthesized on the nanoscale. Although many definitions for nanoparticle exist, from the perspective of size, nanoparticle is defined as particles with diameters less than 100 nm in any external dimension. Examples of their use include titanium dioxide added as a pigment in products intended to be ingested by humans, silicon dioxide NPs are used in foods as an anticaking agent, and gold or iron oxide NPs can be used as vectors for drug delivery or contrast agents for specialized medical imaging. Although the intended use of these NPs is often to improve human health, it has come to the attention of investigators that NPs can have unintended or even detrimental effects on the organism. This work describes one such unintended effect of NP exposure from the perspective of exposure via the oral route. First, this Dissertation will explain an event referred to as brush border disruption that occurred after nanoparticles interacted with an in vitro model of the human intestinal epithelium. Second, this Dissertation will identify and characterize several consumer goods that were shown to contain titanium dioxide that are intended to be ingested. Third, this Dissertation shows that sedimentation due to gravity does not artifactually result in disruption of brush borders as a consequence of exposure to food grade titanium dioxide in vitro. Finally, this Dissertation will demonstrate that iron oxide nanoparticles elicited similar effects after exposure to an in vitro brush border expressing model of the human placenta. Together, these data suggest that brush border disruption is not an artifact of the material/cell culture model, but instead represents a bona fide biological response as a result of exposure to nanomaterial.
ContributorsFaust, James J (Author) / Capco, David G. (Thesis advisor) / Ugarova, Tatiana (Committee member) / Chandler, Douglas (Committee member) / Baluch, Page (Committee member) / Herman, Richard (Committee member) / Arizona State University (Publisher)
Created2014
Description
The NLR family, pyrin domain-containing 3 (NLRP3) inflammasome is essential for the innate immune response to danger signals. Importantly, the NLRP3 inflammasome responds to structurally and functionally dissimilar stimuli. It is currently unknown how the NLRP3 inflammasome responds to such diverse triggers. This dissertation investigates the role of ion flux in regulating the NLRP3 inflammasome. Project 1 explores the relationship between potassium efflux and Syk tyrosine kinase. The results reveal that Syk activity is upstream of mitochondrial oxidative signaling and is crucial for inflammasome assembly, pro-inflammatory cytokine processing, and caspase-1-dependent pyroptotic cell death. Dynamic potassium imaging and molecular analysis revealed that Syk is downstream of, and regulated by, potassium efflux. Project 1 reveals the first identified intermediate regulator of inflammasome activity regulated by potassium efflux. Project 2 focuses on P2X7 purinergic receptor-dependent ion flux in regulating the inflammasome. Dynamic potassium imaging revealed an ATP dose-dependent efflux of potassium driven by P2X7. Surprisingly, ATP induced mitochondrial potassium mobilization, suggesting a mitochondrial detection of purinergic ion flux. ATP-induced potassium and calcium flux was found to regulate mitochondrial oxidative signaling upstream of inflammasome assembly. First-ever multiplexed imaging of potassium and calcium dynamics revealed that potassium efflux is necessary for calcium influx. These results suggest that ATP-induced potassium efflux regulates the inflammasome by calcium influx-dependent mitochondrial oxidative signaling. Project 2 defines a coordinated cation flux dependent on the efflux of potassium and upstream of mitochondrial oxidative signaling in inflammasome regulation. Lastly, this dissertation contributes two methods that will be useful for investigating inflammasome biology: an optimized pipeline for single cell transcriptional analysis, and a mouse macrophage cell line expressing a genetically encoded intracellular ATP sensor. This dissertation contributes to understanding the fundamental role of ion flux in regulation of the NLRP3 inflammasome and identifies potassium flux and Syk as potential targets to modulate inflammation.
ContributorsYaron, Jordan Robin (Author) / Meldrum, Deirdre R (Thesis advisor) / Blattman, Joseph N (Committee member) / Glenn, Honor L (Committee member) / Arizona State University (Publisher)
Created2015
Description
For animals that experience annual cycles of gonad development, the seasonal timing (phenology) of gonad growth is a major adaptation to local environmental conditions. To optimally time seasonal gonad growth, animals use environmental cues that forecast future conditions. The availability of food is one such environmental cue. Although the importance of food availability has been appreciated for decades, the physiological mechanisms underlying the modulation of seasonal gonad growth by this environmental factor remain poorly understood.
Urbanization is characterized by profound environmental changes, and urban animals must adjust to an environment vastly different from that of their non-urban conspecifics. Evidence suggests that birds adjust to urban areas by advancing the timing of seasonal breeding and gonad development, compared to their non-urban conspecifics. A leading hypothesis to account for this phenomenon is that food availability is elevated in urban areas, which improves the energetic status of urban birds and enables them to initiate gonad development earlier than their non-urban conspecifics. However, this hypothesis remains largely untested.
My dissertation dovetailed comparative studies and experimental approaches conducted in field and captive settings to examine the physiological mechanisms by which food availability modulates gonad growth and to investigate whether elevated food availability in urban areas advances the phenology of gonad growth in urban birds. My captive study demonstrated that energetic status modulates reproductive hormone secretion, but not gonad growth. By contrast, free-ranging urban and non-urban birds did not differ in energetic status or plasma levels of reproductive hormones either in years in which urban birds had advanced phenology of gonad growth or in a year that had no habitat-related disparity in seasonal gonad growth. Therefore, my dissertation provides no support for the hypothesis that urban birds begin seasonal gonad growth because they are in better energetic status and increase the secretion of reproductive hormones earlier than non-urban birds. My studies do suggest, however, that the phenology of key food items and the endocrine responsiveness of the reproductive system may contribute to habitat-related disparities in the phenology of gonad growth.
Urbanization is characterized by profound environmental changes, and urban animals must adjust to an environment vastly different from that of their non-urban conspecifics. Evidence suggests that birds adjust to urban areas by advancing the timing of seasonal breeding and gonad development, compared to their non-urban conspecifics. A leading hypothesis to account for this phenomenon is that food availability is elevated in urban areas, which improves the energetic status of urban birds and enables them to initiate gonad development earlier than their non-urban conspecifics. However, this hypothesis remains largely untested.
My dissertation dovetailed comparative studies and experimental approaches conducted in field and captive settings to examine the physiological mechanisms by which food availability modulates gonad growth and to investigate whether elevated food availability in urban areas advances the phenology of gonad growth in urban birds. My captive study demonstrated that energetic status modulates reproductive hormone secretion, but not gonad growth. By contrast, free-ranging urban and non-urban birds did not differ in energetic status or plasma levels of reproductive hormones either in years in which urban birds had advanced phenology of gonad growth or in a year that had no habitat-related disparity in seasonal gonad growth. Therefore, my dissertation provides no support for the hypothesis that urban birds begin seasonal gonad growth because they are in better energetic status and increase the secretion of reproductive hormones earlier than non-urban birds. My studies do suggest, however, that the phenology of key food items and the endocrine responsiveness of the reproductive system may contribute to habitat-related disparities in the phenology of gonad growth.
ContributorsDavies, Scott (Author) / Deviche, Pierre (Thesis advisor) / Sweazea, Karen (Committee member) / McGraw, Kevin (Committee member) / Orchinik, Miles (Committee member) / Warren, Paige (Committee member) / Arizona State University (Publisher)
Created2014
Description
In 1968, phycologist M.R. Droop published his famous discovery on the functional relationship between growth rate and internal nutrient status of algae in chemostat culture. The simple notion that growth is directly dependent on intracellular nutrient concentration is useful for understanding the dynamics in many ecological systems. The cell quota in particular lends itself to ecological stoichiometry, which is a powerful framework for mathematical ecology. Three models are developed based on the cell quota principal in order to demonstrate its applications beyond chemostat culture.
First, a data-driven model is derived for neutral lipid synthesis in green microalgae with respect to nitrogen limitation. This model synthesizes several established frameworks in phycology and ecological stoichiometry. The model demonstrates how the cell quota is a useful abstraction for understanding the metabolic shift to neutral lipid production that is observed in certain oleaginous species.
Next a producer-grazer model is developed based on the cell quota model and nutrient recycling. The model incorporates a novel feedback loop to account for animal toxicity due to accumulation of nitrogen waste. The model exhibits rich, complex dynamics which leave several open mathematical questions.
Lastly, disease dynamics in vivo are in many ways analogous to those of an ecosystem, giving natural extensions of the cell quota concept to disease modeling. Prostate cancer can be modeled within this framework, with androgen the limiting nutrient and the prostate and cancer cells as competing species. Here the cell quota model provides a useful abstraction for the dependence of cellular proliferation and apoptosis on androgen and the androgen receptor. Androgen ablation therapy is often used for patients in biochemical recurrence or late-stage disease progression and is in general initially effective. However, for many patients the cancer eventually develops resistance months to years after treatment begins. Understanding how and predicting when hormone therapy facilitates evolution of resistant phenotypes has immediate implications for treatment. Cell quota models for prostate cancer can be useful tools for this purpose and motivate applications to other diseases.
First, a data-driven model is derived for neutral lipid synthesis in green microalgae with respect to nitrogen limitation. This model synthesizes several established frameworks in phycology and ecological stoichiometry. The model demonstrates how the cell quota is a useful abstraction for understanding the metabolic shift to neutral lipid production that is observed in certain oleaginous species.
Next a producer-grazer model is developed based on the cell quota model and nutrient recycling. The model incorporates a novel feedback loop to account for animal toxicity due to accumulation of nitrogen waste. The model exhibits rich, complex dynamics which leave several open mathematical questions.
Lastly, disease dynamics in vivo are in many ways analogous to those of an ecosystem, giving natural extensions of the cell quota concept to disease modeling. Prostate cancer can be modeled within this framework, with androgen the limiting nutrient and the prostate and cancer cells as competing species. Here the cell quota model provides a useful abstraction for the dependence of cellular proliferation and apoptosis on androgen and the androgen receptor. Androgen ablation therapy is often used for patients in biochemical recurrence or late-stage disease progression and is in general initially effective. However, for many patients the cancer eventually develops resistance months to years after treatment begins. Understanding how and predicting when hormone therapy facilitates evolution of resistant phenotypes has immediate implications for treatment. Cell quota models for prostate cancer can be useful tools for this purpose and motivate applications to other diseases.
ContributorsPacker, Aaron (Author) / Kuang, Yang (Thesis advisor) / Nagy, John (Committee member) / Smith, Hal (Committee member) / Kostelich, Eric (Committee member) / Kang, Yun (Committee member) / Arizona State University (Publisher)
Created2014
Description
This multiple-case study addresses the nature of the out-of-school musical engagements of four undergraduate students who were enrolled as jazz studies majors in a large school of music in the U.S. southwest. It concerns what they did musically when they were outside of school, why they did what they did, what experiences they said they learned from, and how their out-of-school engagements related to their in-school curriculum. Research on jazz education, informal learning practices in music, and the in-school and out-of-school experiences of students informed this study. Data were generated through observation, interviews, video blogs (vlogs), and SMS text messages.
Analysis of data revealed that participants engaged with music when outside of school by practicing, teaching, gigging, recording, playing music with others, attending live musical performances, socializing with other musicians, listening, and engaging with non-jazz musical styles (aside from listening). They engaged with music because of: 1) the love of music, 2) the desire for musical excellence, 3) financial considerations, 4) the aspiration to affect others positively with music, and 5) the connection with other musicians. Participants indicated that they learned by practicing, listening to recordings, attending live performances, playing paid engagements, socializing, teaching, and reading. In-school and out-of-school experience and learning had substantial but not complete overlap.
The study implies that a balance between in-school and out-of-school musical experience may help undergraduate jazz studies students to maximize their overall musical learning. It also suggests that at least some jazz studies majors are fluent in a wide variety of music learning practices that make them versatile, flexible, and employable musicians. Further implications are provided for undergraduate jazz students as well as collegiate jazz educators, the music education profession, and schools of music. Additional implications concern future research and the characterization of jazz study in academia.
Analysis of data revealed that participants engaged with music when outside of school by practicing, teaching, gigging, recording, playing music with others, attending live musical performances, socializing with other musicians, listening, and engaging with non-jazz musical styles (aside from listening). They engaged with music because of: 1) the love of music, 2) the desire for musical excellence, 3) financial considerations, 4) the aspiration to affect others positively with music, and 5) the connection with other musicians. Participants indicated that they learned by practicing, listening to recordings, attending live performances, playing paid engagements, socializing, teaching, and reading. In-school and out-of-school experience and learning had substantial but not complete overlap.
The study implies that a balance between in-school and out-of-school musical experience may help undergraduate jazz studies students to maximize their overall musical learning. It also suggests that at least some jazz studies majors are fluent in a wide variety of music learning practices that make them versatile, flexible, and employable musicians. Further implications are provided for undergraduate jazz students as well as collegiate jazz educators, the music education profession, and schools of music. Additional implications concern future research and the characterization of jazz study in academia.
ContributorsLibman, Jeffrey B (Author) / Tobias, Evan (Thesis advisor) / Kocour, Michael (Committee member) / Schmidt, Margaret (Committee member) / Solis, Theodore (Committee member) / Stauffer, Sandra (Committee member) / Arizona State University (Publisher)
Created2014
Description
Rhodoferax antarcticus strain ANT.BR, a purple nonsulfur bacterium isolated from a microbial mat in Ross Island, Antarctica, is the first described anoxygenic phototrophic bacterium that is adapted to cold habitats and is the first beta-proteobacterium to undergo complete genome sequencing. R. antarcticus has unique absorption spectra and there are no obvious intracytoplasmic membranes in cells grown phototrophically, even under low light intensity. Analysis of the finished genome sequence reveals a single chromosome (3,809,266 bp) and a large plasmid (198,615 bp) that together harbor 4,262 putative genes. The genome contains two types of Rubiscos, Form IAq and Form II, which are known to exhibit quite different kinetic properties in other bacteria. The presence of multiple Rubisco forms could give R. antarcticus high metabolic flexibility in diverse environments. Annotation of the complete genome sequence along with previous experimental results predict the presence of structural genes for three types of light-harvesting (LH) complexes, LH I (B875), LH II (B800/850), and LH III (B800/820). There is evidence that expression of genes for the LH II complex might be inhibited when R. antarcticus is under low temperature and/or low light intensity. These interesting condition-dependent light-harvesting apparatuses and the control of their expression are very valuable for the further understanding of photosynthesis in cold environments. Finally, R. antarcticus exhibits a highly motile lifestyle. The genome content and organization of all putative polar flagella genes are characterized and discussed.
ContributorsZhao, Tingting, M.S (Author) / Touchman, Jeffrey (Thesis advisor) / Rosenberg, Michael (Committee member) / Redding, Kevin (Committee member) / Stout, Valerie (Committee member) / Arizona State University (Publisher)
Created2011
Description
One hypothesis for the small size of insects relative to vertebrates, and the existence of giant fossil insects, is that atmospheric oxygen levels have constrained body sizes because oxygen delivery would be unable to match the needs of metabolically active tissues in larger insects. This study tested whether oxygen delivery becomes more challenging for larger insects by measuring the oxygen-sensitivity of flight metabolic rates and behavior during hovering for 11 different species of dragonflies that range in mass by an order of magnitude. Animals were flown in 7 different oxygen concentrations ranging from 30% to 2.5% to assess the sensitivity of their behavior and flight metabolic rates to oxygen. I also assessed the oxygen-sensitivity of flight in low-density air (nitrogen replaced with helium), to increase the metabolic demands of hovering flight. Lowered atmosphere densities did induce higher metabolic rates. Flight behaviors but not flight metabolic rates were highly oxygen-sensitive. A significant interaction between oxygen and mass was found for total flight time, with larger dragonflies varying flight time more in response to atmospheric oxygen. This study provides some support for the hypothesis that larger insects are more challenged in oxygen delivery, as predicted by the oxygen limitation hypothesis for insect gigantism in the Paleozoic.
ContributorsHenry, Joanna Randyl (Author) / Harrison, Jon F. (Thesis advisor) / Kaiser, Alexander (Committee member) / Rutowski, Ronald L (Committee member) / Arizona State University (Publisher)
Created2011
Biological and immunological characterization of plant-produced HIV-1 Gag/dgp41 virus-like particles
Description
Anti-retroviral drugs and AIDS prevention programs have helped to decrease the rate of new HIV-1 infections in some communities, however, a prophylactic vaccine is still needed to control the epidemic world-wide. Despite over two decades of research, a vaccine against HIV-1 remains elusive, although recent clinical trials have shown promising results. Recent successes have focused on highly conserved, mucosally-targeted antigens within HIV-1 such as the membrane proximal external region (MPER) of the envelope protein, gp41. MPER has been shown to play critical roles in the viral mucosal transmission, though this peptide is not immunogenic on its own. Gag is a structural protein configuring the enveloped virus particles, and has been suggested to constitute a target of the cellular immunity potentially controlling the viral load. It was hypothesized that HIV-1 enveloped virus-like particles (VLPs) consisting of Gag and a deconstructed form of gp41 comprising the MPER, transmembrane, and cytoplasmic domains (dgp41) could be expressed in plants. Plant-optimized HIV-1 genes were constructed and expressed in Nicotiana benthamiana by stable transformation, or transiently using a tobacco mosaic virus-based expression system or a combination of both. Results of biophysical, biochemical and electron microscopy characterization demonstrated that plant cells could support not only the formation of HIV-1 Gag VLPs, but also the accumulation of VLPs that incorporated dgp41. These particles were purified and utilized in mice immunization experiments. Prime-boost strategies combining systemic and mucosal priming with systemic boosting using two different vaccine candidates (VLPs and CTB-MPR - a fusion of MPER and the B-subunit of cholera toxin) were administered to BALB/c mice. Serum antibody responses against both the Gag and gp41 antigens could be elicited in mice systemically primed with VLPs and these responses could be recalled following systemic boosting with VLPs. In addition, mucosal priming with VLPs allowed for a robust boosting response against Gag and gp41 when boosted with either candidate. Functional assays of these antibodies are in progress to test the antibodies' effectiveness in neutralizing and preventing mucosal transmission of HIV-1. This immunogenicity of plant-based Gag/dgp41 VLPs represents an important milestone on the road towards a broadly-efficacious and inexpensive subunit vaccine against HIV-1.
ContributorsKessans, Sarah (Author) / Mor, Tsafrir S (Thesis advisor) / Matoba, Nobuyuki (Committee member) / Mason, Hugh (Committee member) / Hogue, Brenda (Committee member) / Fromme, Petra (Committee member) / Arizona State University (Publisher)
Created2011
Description
The study of artist transcriptions is an effective vehicle for assimilating the language and style of jazz. Pairing transcriptions with historical context provides further insight into the back story of the artists' life and method. Innovators are often the subject of published studies of this kind, but transcriptions of plunger-mute master Al Grey have been overlooked. This document fills that void, combining historical context with thirteen transcriptions of Grey's trombone features and improvisations. Selection of transcribed materials was based on an examination of historically significant solos in Al Grey's fifty-five-year career. The results are a series of open-horn and plunger solos that showcase Grey's sound, technical brilliance, and wide range of dynamics and articulation. This collection includes performances from a mix of widely available and obscure recordings, the majority coming from engagements with the Count Basie Orchestra. Methods learned from the study of Al Grey's book Plunger Techniques were vital in the realization of his work. The digital transcription software Amazing Slow Downer by Roni Music aided in deciphering some of Grey's more complicated passages and, with octave displacement, helped bring previously inaudible moments to the foreground.
ContributorsHopkins, Charles E (Author) / Pilafian, Sam (Thesis advisor) / Stauffer, Sandra (Committee member) / Solís, Ted (Committee member) / Ericson, John (Committee member) / Kocour, Michael (Committee member) / Arizona State University (Publisher)
Created2011
Description
African Swine Fever (ASF), endemic in many African countries, is now spreading to other continents. Though ASF is capable of incurring serious economic losses in affected countries, no vaccine exists to provide immunity to animals. Disease control relies largely on rapid diagnosis and the implementation of movement restrictions and strict eradication programs. Developing a scalable, accurate and low cost diagnostic for ASF will be of great help for the current situation. CIM's 10K random peptide microarray is a new high-throughput platform that allows systematic investigations of immune responses associated with disease and shows promise as a diagnostic tool. In this study, this new technology was applied to characterize the immune responses of ASF virus (ASFV) infections and immunizations. Six sets of sera from ASFV antigen immunized pigs, 6 sera from infected pigs and 20 sera samples from unexposed pigs were tested and analyzed statistically. Results show that both ASFV antigen immunized pigs and ASFV viral infected pigs can be distinguished from unexposed pigs. Since it appears that immune responses to other viral infections are also distinguishable on this platform, it holds the potential of being useful in developing a new ASF diagnostic. The ability of this platform to identify specific ASFV antibody epitopes was also explored. A subtle motif was found to be shared among a set of peptides displaying the highest reactivity for an antigen specific antibody. However, this motif does not seem to match with any antibody epitopes predicted by a linear antibody epitope prediction.
ContributorsXiao, Liang (Author) / Sykes, Kathryn (Thesis advisor) / Zhao, Zhan-Gong (Committee member) / Stafford, Phillip (Committee member) / Arizona State University (Publisher)
Created2011