Matching Items (482)
152348-Thumbnail Image.png
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
151797-Thumbnail Image.png
Description
The study of bacterial resistance to antimicrobial peptides (AMPs) is a significant area of interest as these peptides have the potential to be developed into alternative drug therapies to combat microbial pathogens. AMPs represent a class of host-mediated factors that function to prevent microbial infection of their host and serve

The study of bacterial resistance to antimicrobial peptides (AMPs) is a significant area of interest as these peptides have the potential to be developed into alternative drug therapies to combat microbial pathogens. AMPs represent a class of host-mediated factors that function to prevent microbial infection of their host and serve as a first line of defense. To date, over 1,000 AMPs of various natures have been predicted or experimentally characterized. Their potent bactericidal activities and broad-based target repertoire make them a promising next-generation pharmaceutical therapy to combat bacterial pathogens. It is important to understand the molecular mechanisms, both genetic and physiological, that bacteria employ to circumvent the bactericidal activities of AMPs. These understandings will allow researchers to overcome challenges posed with the development of new drug therapies; as well as identify, at a fundamental level, how bacteria are able to adapt and survive within varied host environments. Here, results are presented from the first reported large scale, systematic screen in which the Keio collection of ~4,000 Escherichia coli deletion mutants were challenged against physiologically significant AMPs to identify genes required for resistance. Less than 3% of the total number of genes on the E. coli chromosome was determined to contribute to bacterial resistance to at least one AMP analyzed in the screen. Further, the screen implicated a single cellular component (enterobacterial common antigen, ECA) and a single transporter system (twin-arginine transporter, Tat) as being required for resistance to each AMP class. Using antimicrobial resistance as a tool to identify novel genetic mechanisms, subsequent analyses were able to identify a two-component system, CpxR/CpxA, as a global regulator in bacterial resistance to AMPs. Multiple previously characterized CpxR/A members, as well as members found in this study, were identified in the screen. Notably, CpxR/A was found to transcriptionally regulate the gene cluster responsible for the biosynthesis of the ECA. Thus, a novel genetic mechanism was uncovered that directly correlates with a physiologically significant cellular component that appears to globally contribute to bacterial resistance to AMPs.
ContributorsWeatherspoon-Griffin, Natasha (Author) / Shi, Yixin (Thesis advisor) / Clark-Curtiss, Josephine (Committee member) / Misra, Rajeev (Committee member) / Nickerson, Cheryl (Committee member) / Stout, Valerie (Committee member) / Arizona State University (Publisher)
Created2013
151748-Thumbnail Image.png
Description
For over a century, researchers have been investigating collective cognition, in which a group of individuals together process information and act as a single cognitive unit. However, I still know little about circumstances under which groups achieve better (or worse) decisions than individuals. My dissertation research directly addressed this longstanding

For over a century, researchers have been investigating collective cognition, in which a group of individuals together process information and act as a single cognitive unit. However, I still know little about circumstances under which groups achieve better (or worse) decisions than individuals. My dissertation research directly addressed this longstanding question, using the house-hunting ant Temnothorax rugatulus as a model system. Here I applied concepts and methods developed in psychology not only to individuals but also to colonies in order to investigate differences of their cognitive abilities. This approach is inspired by the superorganism concept, which sees a tightly integrated insect society as the analog of a single organism. I combined experimental manipulations and models to elucidate the emergent processes of collective cognition. My studies show that groups can achieve superior cognition by sharing the burden of option assessment among members and by integrating information from members using positive feedback. However, the same positive feedback can lock the group into a suboptimal choice in certain circumstances. Although ants are obligately social, my results show that they can be isolated and individually tested on cognitive tasks. In the future, this novel approach will help the field of animal behavior move towards better understanding of collective cognition.
ContributorsSasaki, Takao (Author) / Pratt, Stephen C (Thesis advisor) / Amazeen, Polemnia (Committee member) / Liebig, Jürgen (Committee member) / Janssen, Marco (Committee member) / Fewell, Jennifer (Committee member) / Hölldobler, Bert (Committee member) / Arizona State University (Publisher)
Created2013
151725-Thumbnail Image.png
Description
Woody plant encroachment is a worldwide phenomenon linked to water availability in semiarid systems. Nevertheless, the implications of woody plant encroachment on the hydrologic cycle are poorly understood, especially at the catchment scale. This study takes place in a pair of small semiarid rangeland undergoing the encroachment of Prosopis velutina

Woody plant encroachment is a worldwide phenomenon linked to water availability in semiarid systems. Nevertheless, the implications of woody plant encroachment on the hydrologic cycle are poorly understood, especially at the catchment scale. This study takes place in a pair of small semiarid rangeland undergoing the encroachment of Prosopis velutina Woot., or velvet mesquite tree. The similarly-sized basins are in close proximity, leading to equivalent meteorological and soil conditions. One basin was treated for mesquite in 1974, while the other represents the encroachment process. A sensor network was installed to measure ecohydrological states and fluxes, including precipitation, runoff, soil moisture and evapotranspiration. Observations from June 1, 2011 through September 30, 2012 are presented to describe the seasonality and spatial variability of ecohydrological conditions during the North American Monsoon (NAM). Runoff observations are linked to historical changes in runoff production in each watershed. Observations indicate that the mesquite-treated basin generates more runoff pulses and greater runoff volume for small rainfall events, while the mesquite-encroached basin generates more runoff volume for large rainfall events. A distributed hydrologic model is applied to both basins to investigate the runoff threshold processes experienced during the NAM. Vegetation in the two basins is classified into grass, mesquite, or bare soil using high-resolution imagery. Model predictions are used to investigate the vegetation controls on soil moisture, evapotranspiration, and runoff generation. The distributed model shows that grass and mesquite sites retain the highest levels of soil moisture. The model also captures the runoff generation differences between the two watersheds that have been observed over the past decade. Generally, grass sites in the mesquite-treated basin have less plant interception and evapotranspiration, leading to higher soil moisture that supports greater runoff for small rainfall events. For large rainfall events, the mesquite-encroached basin produces greater runoff due to its higher fraction of bare soil. The results of this study show that a distributed hydrologic model can be used to explain runoff threshold processes linked to woody plant encroachment at the catchment-scale and provides useful interpretations for rangeland management in semiarid areas.
ContributorsPierini, Nicole A (Author) / Vivoni, Enrique R (Thesis advisor) / Wang, Zhi-Hua (Committee member) / Mays, Larry W. (Committee member) / Arizona State University (Publisher)
Created2013
151119-Thumbnail Image.png
Description
The spread of invasive species may be greatly affected by human responses to prior species spread, but models and estimation methods seldom explicitly consider human responses. I investigate the effects of management responses on estimates of invasive species spread rates. To do this, I create an agent-based simulation model of

The spread of invasive species may be greatly affected by human responses to prior species spread, but models and estimation methods seldom explicitly consider human responses. I investigate the effects of management responses on estimates of invasive species spread rates. To do this, I create an agent-based simulation model of an insect invasion across a county-level citrus landscape. My model provides an approximation of a complex spatial environment while allowing the "truth" to be known. The modeled environment consists of citrus orchards with insect pests dispersing among them. Insects move across the simulation environment infesting orchards, while orchard managers respond by administering insecticide according to analyst-selected behavior profiles and management responses may depend on prior invasion states. Dispersal data is generated in each simulation and used to calculate spread rate via a set of estimators selected for their predominance in the empirical literature. Spread rate is a mechanistic, emergent phenomenon measured at the population level caused by a suite of latent biological, environmental, and anthropogenic. I test the effectiveness of orchard behavior profiles on invasion suppression and evaluate the robustness of the estimators given orchard responses. I find that allowing growers to use future expectations of spread in management decisions leads to reduced spread rates. Acting in a preventative manner by applying insecticide before insects are actually present, orchards are able to lower spread rates more than by reactive behavior alone. Spread rates are highly sensitive to spatial configuration. Spatial configuration is hardly a random process, consisting of many latent factors often not accounted for in spread rate estimation. Not considering these factors may lead to an omitted variables bias and skew estimation results. The ability of spread rate estimators to predict future spread varies considerably between estimators, and with spatial configuration, invader biological parameters, and orchard behavior profile. The model suggests that understanding the latent factors inherent to dispersal is important for selecting phenomenological models of spread and interpreting estimation results. This indicates a need for caution when evaluating spread. Although standard practice, current empirical estimators may both over- and underestimate spread rate in the simulation.
ContributorsShanafelt, David William (Author) / Fenichel, Eli P (Thesis advisor) / Richards, Timothy (Committee member) / Janssen, Marco (Committee member) / Arizona State University (Publisher)
Created2012
136287-Thumbnail Image.png
Description
Hepatitis C virus (HCV) is a globally prevalent infection which is a main contributor to the global burden of liver disease. Due to its ability to establish a chronic infection, and the lack of usefulness of traditional neutralizing antibody vaccine design in producing a protective immune response, a preventative vaccine

Hepatitis C virus (HCV) is a globally prevalent infection which is a main contributor to the global burden of liver disease. Due to its ability to establish a chronic infection, and the lack of usefulness of traditional neutralizing antibody vaccine design in producing a protective immune response, a preventative vaccine has been notoriously difficult to produce. To overcome this, a vaccine using non-structural protein 3 (NS3) as a target to elicit a T cell specific immune response is thought to be a possible strategy for eliciting a protective immune response against hepatitis C infection. In this paper, a recombinant strain of measles virus (MV) that expresses HCV NS3 protein was analyzed. The replication fitness of this recombinant virus also indicates that this construct replicates at a higher rate than parental measles strain. It is also demonstrated through western blot analysis of protein expression and immunofluorescence that this recombinant virus expresses both the inserted HCV NS3 protein, as well as native measles proteins.
ContributorsWoell, Dana Marie (Author) / Reyes del Valle, Jorge (Thesis director) / Nickerson, Cheryl (Committee member) / Julik, Emily (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / School of Human Evolution and Social Change (Contributor)
Created2015-05
135647-Thumbnail Image.png
Description
Clean water for drinking, food preparation, and bathing is essential for astronaut health and safety during long duration habitation of the International Space Station (ISS), including future missions to Mars. Despite stringent water treatment and recycling efforts on the ISS, it is impossible to completely prevent microbial contamination of onboard

Clean water for drinking, food preparation, and bathing is essential for astronaut health and safety during long duration habitation of the International Space Station (ISS), including future missions to Mars. Despite stringent water treatment and recycling efforts on the ISS, it is impossible to completely prevent microbial contamination of onboard water supplies. In this work, we used a spaceflight analogue culture system to better understand how the microgravity environment can influence the pathogenesis-related characteristics of Burkholderia cepacia complex (Bcc), an opportunistic pathogen previously recovered from the ISS water system. The results of the present study suggest that there may be important differences in how this pathogen can respond and adapt to spaceflight and other low fluid shear environments encountered during their natural life cycles. Future studies are aimed at understanding the underlying mechanisms responsible for these phenotypes.
ContributorsKang, Bianca Younseon (Author) / Nickerson, Cheryl (Thesis director) / Barrila, Jennifer (Committee member) / Ott, Mark (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
137493-Thumbnail Image.png
DescriptionThis paper provides an analysis of the differences in impacts made by companies that promote their sustainability efforts. A comparison of companies reveals that the ones with greater supply chain influence and larger consumer bases can make more concrete progress in terms of accomplishment for the sustainability realm.
ContributorsBeaubien, Courtney Lynn (Author) / Anderies, John (Thesis director) / Allenby, Brad (Committee member) / Janssen, Marco (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2013-05
141440-Thumbnail Image.png
Description

Engineered pavements cover a large fraction of cities and offer significant potential for urban heat island mitigation. Though rapidly increasing research efforts have been devoted to the study of pavement materials, thermal interactions between buildings and the ambient environment are mostly neglected. In this study, numerical models featuring a realistic

Engineered pavements cover a large fraction of cities and offer significant potential for urban heat island mitigation. Though rapidly increasing research efforts have been devoted to the study of pavement materials, thermal interactions between buildings and the ambient environment are mostly neglected. In this study, numerical models featuring a realistic representation of building-environment thermal interactions, were applied to quantify the effect of pavements on the urban thermal environment at multiple scales. It was found that performance of pavements inside the canyon was largely determined by the canyon geometry. In a high-density residential area, modifying pavements had insignificant effect on the wall temperature and building energy consumption. At a regional scale, various pavement types were also found to have a limited cooling effect on land surface temperature and 2-m air temperature for metropolitan Phoenix. In the context of global climate change, the effect of pavement was evaluated in terms of the equivalent CO2 emission. Equivalent CO2 emission offset by reflective pavements in urban canyons was only about 13.9e46.6% of that without building canopies, depending on the canyon geometry. This study revealed the importance of building-environment thermal interactions in determining thermal conditions inside the urban canopy.

ContributorsYang, Jiachuan (Author) / Wang, Zhi-Hua (Author) / Kaloush, Kamil (Author) / Dylla, Heather (Author)
Created2016-08-22
141462-Thumbnail Image.png
Description

Despite the fact that seizures are commonly associated with autism spectrum disorder (ASD), the effectiveness of treatments for seizures has not been well studied in individuals with ASD. This manuscript reviews both traditional and novel treatments for seizures associated with ASD. Studies were selected by systematically searching major electronic databases

Despite the fact that seizures are commonly associated with autism spectrum disorder (ASD), the effectiveness of treatments for seizures has not been well studied in individuals with ASD. This manuscript reviews both traditional and novel treatments for seizures associated with ASD. Studies were selected by systematically searching major electronic databases and by a panel of experts that treat ASD individuals. Only a few anti-epileptic drugs (AEDs) have undergone carefully controlled trials in ASD, but these trials examined outcomes other than seizures. Several lines of evidence point to valproate, lamotrigine, and levetiracetam as the most effective and tolerable AEDs for individuals with ASD. Limited evidence supports the use of traditional non-AED treatments, such as the ketogenic and modified Atkins diet, multiple subpial transections, immunomodulation, and neurofeedback treatments. Although specific treatments may be more appropriate for specific genetic and metabolic syndromes associated with ASD and seizures, there are few studies which have documented the effectiveness of treatments for seizures for specific syndromes. Limited evidence supports l-carnitine, multivitamins, and N-acetyl-l-cysteine in mitochondrial disease and dysfunction, folinic acid in cerebral folate abnormalities and early treatment with vigabatrin in tuberous sclerosis complex. Finally, there is limited evidence for a number of novel treatments, particularly magnesium with pyridoxine, omega-3 fatty acids, the gluten-free casein-free diet, and low-frequency repetitive transcranial magnetic simulation. Zinc and l-carnosine are potential novel treatments supported by basic research but not clinical studies. This review demonstrates the wide variety of treatments used to treat seizures in individuals with ASD as well as the striking lack of clinical trials performed to support the use of these treatments. Additional studies concerning these treatments for controlling seizures in individuals with ASD are warranted.

ContributorsFrye, Richard E. (Author) / Rossignol, Daniel (Author) / Casanova, Manuel F. (Author) / Brown, Gregory L. (Author) / Martin, Victoria (Author) / Edelson, Stephen (Author) / Coben, Robert (Author) / Lewine, Jeffrey (Author) / Slattery, John C. (Author) / Lau, Chrystal (Author) / Hardy, Paul (Author) / Fatemi, S. Hossein (Author) / Folsom, Timothy D. (Author) / MacFabe, Derrick (Author) / Adams, James (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2013-09-13