Matching Items (124)
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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
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
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Description
Droughts are a common phenomenon of the arid South-west USA climate. Despite water limitations, the region has been substantially transformed by agriculture and urbanization. The water requirements to support these human activities along with the projected increase in droughts intensity and frequency challenge long term sustainability and water security, thus

Droughts are a common phenomenon of the arid South-west USA climate. Despite water limitations, the region has been substantially transformed by agriculture and urbanization. The water requirements to support these human activities along with the projected increase in droughts intensity and frequency challenge long term sustainability and water security, thus the need to spatially and temporally characterize land use/land cover response to drought and quantify water consumption is crucial. This dissertation evaluates changes in `undisturbed' desert vegetation in response to water availability to characterize climate-driven variability. A new model coupling phenology and spectral unmixing was applied to Landsat time series (1987-2010) in order to derive fractional cover (FC) maps of annuals, perennials, and evergreen vegetation. Results show that annuals FC is controlled by short term water availability and antecedent soil moisture. Perennials FC follow wet-dry multi-year regime shifts, while evergreen is completely decoupled from short term changes in water availability. Trend analysis suggests that different processes operate at the local scale. Regionally, evergreen cover increased while perennials and annuals cover decreased. Subsequently, urban land cover was compared with its surrounding desert. A distinct signal of rain use efficiency and aridity index was documented from remote sensing and a soil-water-balance model. It was estimated that a total of 295 mm of water input is needed to sustain current greenness. Finally, an energy balance model was developed to spatio-temporally estimate evapotranspiration (ET) as a proxy for water consumption, and evaluate land use/land cover types in response to drought. Agricultural fields show an average ET of 9.3 mm/day with no significant difference between drought and wet conditions, implying similar level of water usage regardless of climatic conditions. Xeric neighborhoods show significant variability between dry and wet conditions, while mesic neighborhoods retain high ET of 400-500 mm during drought due to irrigation. Considering the potentially limited water availability, land use/land cover changes due to population increases, and the threat of a warming and drying climate, maintaining large water-consuming, irrigated landscapes challenges sustainable practices of water conservation and the need to provide amenities of this desert area for enhancing quality of life.
ContributorsKaplan, Shai (Author) / Myint, Soe Win (Thesis advisor) / Brazel, Anthony J. (Committee member) / Georgescu, Matei (Committee member) / Arizona State University (Publisher)
Created2014
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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
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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
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Description
Urban areas produce an urban heat island (UHI), which is manifest as warmer temperatures compared to the surrounding and less developed areas. While it is understood that UHI's are warmer than their surrounding areas, attributing the amount of heat added by the urban area is not easily determined. Current generation

Urban areas produce an urban heat island (UHI), which is manifest as warmer temperatures compared to the surrounding and less developed areas. While it is understood that UHI's are warmer than their surrounding areas, attributing the amount of heat added by the urban area is not easily determined. Current generation modeling systems require diurnal anthropogenic heating profiles. Development of diurnal cycle profiles of anthropogenic heating will help the modeling community as there is currently no database for anthropogenic heating profiles for cities across the United States. With more accurate anthropogenic heating profiles, climate models will be better able to show how humans directly impact the urban climate. This research attempts to create anthropogenic heating profiles for 61 cities in the United States. The method used climate, electricity, natural gas, and transportation data to develop anthropogenic heating profiles for each state. To develop anthropogenic heating profiles, profiles are developed for buildings, transportation, and human metabolism using the most recently available data. Since utilities are reluctant to release data, the building energy profile is developed using statewide electricity by creating a linear regression between the climate and electricity usage. A similar method is used to determine the contribution of natural gas consumption. These profiles are developed for each month of the year, so annual changes in anthropogenic heating can be seen. These profiles can then be put into climate models to enable more accurate urban climate modeling.
ContributorsMilne, Jeffrey (Author) / Georgescu, Matei (Thesis director) / Sailor, David (Committee member) / Brazel, Anthony (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / School of Geographical Sciences and Urban Planning (Contributor)
Created2014-05
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Description

Modeling results incorporating several distinct urban expansion futures for the United States in 2100 show that, in the absence of any adaptive urban design, megapolitan expansion, alone and separate from greenhouse gas-induced forcing, can be expected to raise near-surface temperatures 1–2 °C not just at the scale of individual cities

Modeling results incorporating several distinct urban expansion futures for the United States in 2100 show that, in the absence of any adaptive urban design, megapolitan expansion, alone and separate from greenhouse gas-induced forcing, can be expected to raise near-surface temperatures 1–2 °C not just at the scale of individual cities but over large regional swaths of the country. This warming is a significant fraction of the 21st century greenhouse gas-induced climate change simulated by global climate models. Using a suite of regional climate simulations, we assessed the efficacy of commonly proposed urban adaptation strategies, such as green, cool roof, and hybrid approaches, to ameliorate the warming. Our results quantify how judicious choices in urban planning and design cannot only counteract the climatological impacts of the urban expansion itself but also, can, in fact, even offset a significant percentage of future greenhouse warming over large scales. Our results also reveal tradeoffs among different adaptation options for some regions, showing the need for geographically appropriate strategies rather than one size fits all solutions.

ContributorsGeorgescu, Matei (Author) / Morefield, Philip E. (Author) / Bierwagen, Britta G. (Author) / Weaver, Christopher P. (Author)
Created2014-02-25
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Because of a projected surge of several billion urban inhabitants by mid-century, a rising urgency exists to advance local and strategically deployed measures intended to ameliorate negative consequences on urban climate (e.g., heat stress, poor air quality, energy/water availability). Here we highlight the importance of incorporating scale-dependent built environment induced

Because of a projected surge of several billion urban inhabitants by mid-century, a rising urgency exists to advance local and strategically deployed measures intended to ameliorate negative consequences on urban climate (e.g., heat stress, poor air quality, energy/water availability). Here we highlight the importance of incorporating scale-dependent built environment induced solutions within the broader umbrella of urban sustainability outcomes, thereby accounting for fundamental physical principles. Contemporary and future design of settlements demands cooperative participation between planners, architects, and relevant stakeholders, with the urban and global climate community, which recognizes the complexity of the physical systems involved and is ideally fit to quantitatively examine the viability of proposed solutions. Such participatory efforts can aid the development of locally sensible approaches by integrating across the socioeconomic and climatic continuum, therefore providing opportunities facilitating comprehensive solutions that maximize benefits and limit unintended consequences.

ContributorsGeorgescu, Matei (Author) / Chow, Winston, 1951- (Author) / Brazel, Anthony J. (Author) / Trapido-Lurie, B (Author) / Roth, M (Author) / Benson-Lira, V (Author)
Created2015-06-09
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Description

Conversion of natural to urban land forms imparts influence on local and regional hydroclimate via modification of the surface energy and water balance, and consideration of such effects due to rapidly expanding megapolitan areas is necessary in light of the growing global share of urban inhabitants. Based on a suite

Conversion of natural to urban land forms imparts influence on local and regional hydroclimate via modification of the surface energy and water balance, and consideration of such effects due to rapidly expanding megapolitan areas is necessary in light of the growing global share of urban inhabitants. Based on a suite of ensemble-based, multi-year simulations using the Weather Research and Forecasting (WRF) model, we quantify seasonally varying hydroclimatic impacts of the most rapidly expanding megapolitan area in the US: Arizona's Sun Corridor, centered upon the Greater Phoenix metropolitan area. Using a scenario-based urban expansion approach that accounts for the full range of Sun Corridor growth uncertainty through 2050, we show that built environment induced warming for the maximum development scenario is greatest during the summer season (regionally averaged warming over AZ exceeds 1 °C).

Warming remains significant during the spring and fall seasons (regionally averaged warming over AZ approaches 0.9 °C during both seasons), and is least during the winter season (regionally averaged warming over AZ of 0.5 °C). Impacts from a minimum expansion scenario are reduced, with regionally averaged warming ranging between 0.1 and 0.3 °C for all seasons except winter, when no warming impacts are diagnosed. Integration of highly reflective cool roofs within the built environment, increasingly recognized as a cost-effective option intended to offset the warming influence of urban complexes, reduces urban-induced warming considerably. However, impacts on the hydrologic cycle are aggravated via enhanced evapotranspiration reduction, leading to a 4% total accumulated precipitation decrease relative to the non-adaptive maximum expansion scenario. Our results highlight potentially unintended consequences of this adaptation approach within rapidly expanding megapolitan areas, and emphasize the need for undeniably sustainable development paths that account for hydrologic impacts in addition to continued focus on mean temperature effects.

ContributorsGeorgescu, Matei (Author) / Mahalov, A. (Author) / Moustaoui, M. (Author)
Created2012-09-07
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Description

This research evaluates the climatic summertime representation of the diurnal cycle of near-surface temperature using the Weather Research and Forecasting System (WRF) over the rapidly urbanizing and water-vulnerable Phoenix metropolitan area. A suite of monthly, high-resolution (2 km grid spacing) simulations are conducted during the month of July with both

This research evaluates the climatic summertime representation of the diurnal cycle of near-surface temperature using the Weather Research and Forecasting System (WRF) over the rapidly urbanizing and water-vulnerable Phoenix metropolitan area. A suite of monthly, high-resolution (2 km grid spacing) simulations are conducted during the month of July with both a contemporary landscape and a hypothetical presettlement scenario. WRF demonstrates excellent agreement in the representation of the daily to monthly diurnal cycle of near-surface temperatures, including the accurate simulation of maximum daytime temperature timing. Thermal sensitivity to anthropogenic land use and land cover change (LULCC), assessed via replacement of the modern-day landscape with natural shrubland, is small on the regional scale. The WRF-simulated characterization of the diurnal cycle, supported by previous observational analyses, illustrates two distinct and opposing impacts on the urbanized diurnal cycle of the Phoenix metro area, with evening and nighttime warming partially offset by daytime cooling. The simulated nighttime urban heat island (UHI) over this semiarid urban complex is explained by well-known mechanisms (slow release of heat from within the urban fabric stored during daytime and increased emission of longwave radiation from the urban canopy toward the surface). During daylight hours, the limited vegetation and dry semidesert region surrounding metro Phoenix warms at greater rates than the urban complex. Although prior work has suggested that daytime temperatures are lower within the urban complex owing to the addition of residential and agricultural irrigation (i.e., “oasis effect”) we show that modification of Phoenix's surrounding environment to a biome more representative of temperate regions eliminates the daytime urban cooling. Our results indicate that surrounding environmental conditions, including land cover and availability of soil moisture, play a principal role in establishing the nature and evolution of the diurnal cycle of near-surface temperature for the greater Phoenix, Arizona, metropolitan area relative to its rural and undeveloped counterpart.

ContributorsGeorgescu, Matei (Author) / Moustaoui, M. (Author) / Mahalov, A. (Author) / Dudhia, J. (Author)
Created2011-12-11