Matching Items (33)
154702-Thumbnail Image.png
Description
Despite the safe and effective use of attenuated vaccines for over fifty years, measles virus (MV) remains an insidious threat to global health. Problematically, infants less than one year of age, who are the most prone to severe infection and death by measles, cannot be immunized using current MV vaccines.

Despite the safe and effective use of attenuated vaccines for over fifty years, measles virus (MV) remains an insidious threat to global health. Problematically, infants less than one year of age, who are the most prone to severe infection and death by measles, cannot be immunized using current MV vaccines. For this dissertation, I generated and performed preclinical evaluation of two novel MV vaccine candidates. Based on data from clinical trials that showed increasing the dosage of current MV vaccines improved antibody responses in six-month-old recipients, I hypothesized that increasing the relevant antigenic stimulus of a standard titer dose would allow safe and effective immunization at a younger age. I generated two modified MVs with increased expression of the hemagglutinin (H) protein, the most important viral antigen for inducing protective neutralizing immunity, in the background of a current vaccine-equivalent. One virus, MVvac2-H2, expressed higher levels of full-length H, resulting in a three-fold increase in H incorporation into virions, while the second, MVvac2-Hsol, expressed and secreted truncated, soluble H protein to its extracellular environment. The alteration to the virion envelope of MVvac2-H2 conferred upon that virus a measurable resistance to in vitro neutralization. In initial screening in adult mouse models of vaccination, both modified MVs proved more immunogenic than their parental strain in outbred mice, while MVvac2-H2 additionally proved more immunogenic in the gold standard MV-susceptible mouse model. Remarkably, MVvac2-H2 better induced protective immunity in the presence of low levels of artificially introduced passive immunity that mimic the passive maternal immunity that currently limits vaccination of young infants, and that strongly inhibited responses to the current vaccine-equivalent. Finally, I developed a more physiological infant-like mouse model for MV vaccine testing, in which MV-susceptible dams vaccinated with the current vaccine-equivalent transfer passive immunity to their pups. This model will allow additional preclinical evaluation of the performance of MVvac2-H2 in pups of immune dams. Altogether, in this dissertation I identify a promising candidate, MVvac2-H2, for a next generation measles vaccine.
ContributorsJulik, Emily (Author) / Reyes del Valle, Jorge (Thesis advisor) / Chang, Yung (Committee member) / Blattman, Joseph (Committee member) / Hogue, Brenda (Committee member) / Nickerson, Cheryl (Committee member) / Arizona State University (Publisher)
Created2016
155898-Thumbnail Image.png
Description
Many Fic domain proteins, through catalyzing post translational modifications (PTM) of protein substrates, functionally contribute to bacterial pathogenesis and the regulation of bacterial growth. Furthermore, one form of Fic-mediated regulation is the Fic toxin-antitoxin system, whereby an antitoxin interacts with and inhibits the Fic toxin. This study sought to determine

Many Fic domain proteins, through catalyzing post translational modifications (PTM) of protein substrates, functionally contribute to bacterial pathogenesis and the regulation of bacterial growth. Furthermore, one form of Fic-mediated regulation is the Fic toxin-antitoxin system, whereby an antitoxin interacts with and inhibits the Fic toxin. This study sought to determine the functional importance of Mycobacterium tuberculosis Fic and its putative antitoxin protein, Rv3642c. Using M. tuberculosis H37Rv genetic deletion mutants, fic and Rv3642c were demonstrated to promote intracellular survival in human THP-1 macrophage-like cells. Unlike other Fic toxins, of Fic toxin-antitoxin systems, Fic did not inhibit bacterial growth in vitro in the absence of Rv3642c. Notably, Fic demonstrated in vitro AMPylation of a THP-1 cell extract protein as shown by immunodetection. Fic also exhibited auto-AMPylation activity. Interestingly, a mutation of the conserved histidine in the Fic domain motif, a residue previously shown to be critical for AMPylation, had no effect on Fic-mediated ATP hydrolysis or AMPylation activity. Rv3642c was demonstrated to form a complex with Fic when co-expressed in Escherichia coli, indicating a toxin-antitoxin interaction. Screening M. tuberculosis protein fractions and culture filtrate with α-Fic and α-Rv3642c rabbit antisera did not detect monomers of Fic or Rv3642c, thus the cellular localization of Fic and the Rv3642c-Fic complex remains unclear. The results of this study provide insight into the function of M. tuberculosis Fic, and suggest that Fic and Rv3642c are important for M. tuberculosis survival in the intracellular macrophage environment. Furthermore, these findings challenge the current dogma that Fic domain catalysis is dependent on the conserved histidine of the Fic motif.
ContributorsLaMarca, Ryan (Author) / Haydel, Shelley (Thesis advisor) / Lake, Douglas (Committee member) / Nickerson, Cheryl (Committee member) / Arizona State University (Publisher)
Created2017
157913-Thumbnail Image.png
Description
Understanding how microorganisms adapt and respond to the microgravity environment of spaceflight is important for the function and integrity of onboard life support systems, astronaut health and mission success. Microbial contamination of spacecraft Environmental Life Support Systems (ECLSS), including the potable water system, are well documented and have caused major

Understanding how microorganisms adapt and respond to the microgravity environment of spaceflight is important for the function and integrity of onboard life support systems, astronaut health and mission success. Microbial contamination of spacecraft Environmental Life Support Systems (ECLSS), including the potable water system, are well documented and have caused major disruption to spaceflight missions. The potable water system on the International Space Station (ISS) uses recycled wastewater purified by multiple processes so it is safe for astronaut consumption and personal hygiene. However, despite stringent antimicrobial treatments, multiple bacterial species and biofilms have been recovered from this potable water system. This finding raises concern for crew health risks, vehicle operations and ECLSS system integrity during exploration missions. These concerns are further heightened given that 1) potential pathogens have been isolated from the ISS potable water system, 2) the immune response of astronauts is blunted during spaceflight, 3) spaceflight induces unexpected alterations in microbial responses, including growth and biofilm formation, antimicrobial resistance, stress responses, and virulence, and 4) different microbial phenotypes are often observed between reductionistic pure cultures as compared to more complex multispecies co-cultures, the latter of which are more representative of natural environmental conditions. To advance the understanding of the impact of microgravity on microbial responses that could negatively impact spacecraft ECLSS systems and crew health, this study characterized a range of phenotypic profiles in both pure and co-cultures of bacterial isolates collected from the ISS potable water system between 2009 and 2014. Microbial responses profiled included population dynamics, resistance to silver, biofilm formation, and in vitro colonization of intestinal epithelial cells. Growth characteristics and antibiotic sensitivities for bacterial strains were evaluated to develop selective and/or differential media that allow for isolation of a pure culture from co-cultures, which was critical for the success of this study. Bacterial co-culture experiments were performed using dynamic Rotating Wall Vessel (RWV) bioreactors under spaceflight analogue (Low Shear Modeled Microgravity/LSMMG) and control conditions. These experiments indicated changes in fluid shear have minimal impact on strain recovery. The antimicrobial efficacy of silver on both sessile co-cultures, grown on 316L stainless steel coupons, and planktonic co-cultures showed that silver did not uniformly reduce the recovery of all strains; however, it had a stronger antimicrobial effect on biofilm cultures than planktonic cultures. The impact of silver on the ability of RWV cultured planktonic and biofilm bacterial co-cultures to colonize human intestinal epithelial cells showed that, those strains which were impacted by silver treatment, often increased adherence to the monolayer. Results from these studies provide insight into the dynamics of polymicrobial community interactions, biofilm formation and survival mechanisms of ISS potable water isolates, with potential application for future design of ECLSS systems for sustainable human space exploration.
ContributorsKing, Olivia G (Author) / Nickerson, Cheryl (Thesis advisor) / Barrila, Jennifer (Committee member) / Ott, C (Committee member) / Yang, Jiseon (Committee member) / Arizona State University (Publisher)
Created2019
129422-Thumbnail Image.png
Description

Faced with numerous seemingly intractable social and environmental challenges, many scholars and practitioners are increasingly interested in understanding how to actively engage and transform the existing systems holding such problems in place. Although a variety of analytical models have emerged in recent years, most emphasize either the social or ecological

Faced with numerous seemingly intractable social and environmental challenges, many scholars and practitioners are increasingly interested in understanding how to actively engage and transform the existing systems holding such problems in place. Although a variety of analytical models have emerged in recent years, most emphasize either the social or ecological elements of such transformations rather than their coupled nature. To address this, first we have presented a definition of the core elements of a social-ecological system (SES) that could potentially be altered in a transformation. Second, we drew on insights about transformation from three branches of literature focused on radical change, i.e., social movements, socio-technical transitions, and social innovation, and gave consideration to the similarities and differences with the current studies by resilience scholars. Drawing on these findings, we have proposed a framework that outlines the process and phases of transformative change in an SES. Future research will be able to utilize the framework as a tool for analyzing the alteration of social-ecological feedbacks, identifying critical barriers and leverage points and assessing the outcome of social-ecological transformations.

ContributorsMoore, Michele-Lee (Author) / Tjornbo, Ola (Author) / Enfors, Elin (Author) / Knapp, Corrie (Author) / Hodbod, Jennifer (Author) / Baggio, Jacopo (Author) / Norstrom, Albert (Author) / Olsson, Per (Author) / Biggs, Duan (Author) / Julie Ann Wrigley Global Institute of Sustainability (Contributor)
Created2013-11-30
128778-Thumbnail Image.png
Description

Online communities are becoming increasingly important as platforms for large-scale human cooperation. These communities allow users seeking and sharing professional skills to solve problems collaboratively. To investigate how users cooperate to complete a large number of knowledge-producing tasks, we analyze Stack Exchange, one of the largest question and answer systems

Online communities are becoming increasingly important as platforms for large-scale human cooperation. These communities allow users seeking and sharing professional skills to solve problems collaboratively. To investigate how users cooperate to complete a large number of knowledge-producing tasks, we analyze Stack Exchange, one of the largest question and answer systems in the world. We construct attention networks to model the growth of 110 communities in the Stack Exchange system and quantify individual answering strategies using the linking dynamics on attention networks. We identify two answering strategies. Strategy A aims at performing maintenance by doing simple tasks, whereas strategy B aims at investing time in doing challenging tasks. Both strategies are important: empirical evidence shows that strategy A decreases the median waiting time for answers and strategy B increases the acceptance rate of answers. In investigating the strategic persistence of users, we find that users tends to stick on the same strategy over time in a community, but switch from one strategy to the other across communities. This finding reveals the different sets of knowledge and skills between users. A balance between the population of users taking A and B strategies that approximates 2:1, is found to be optimal to the sustainable growth of communities.

ContributorsWu, Lingfei (Author) / Baggio, Jacopo (Author) / Janssen, Marco (Author) / ASU-SFI Center for Biosocial Complex Systems (Contributor)
Created2016-03-02
Description

On-going efforts to understand the dynamics of coupled social-ecological (or more broadly, coupled infrastructure) systems and common pool resources have led to the generation of numerous datasets based on a large number of case studies. This data has facilitated the identification of important factors and fundamental principles which increase our

On-going efforts to understand the dynamics of coupled social-ecological (or more broadly, coupled infrastructure) systems and common pool resources have led to the generation of numerous datasets based on a large number of case studies. This data has facilitated the identification of important factors and fundamental principles which increase our understanding of such complex systems. However, the data at our disposal are often not easily comparable, have limited scope and scale, and are based on disparate underlying frameworks inhibiting synthesis, meta-analysis, and the validation of findings. Research efforts are further hampered when case inclusion criteria, variable definitions, coding schema, and inter-coder reliability testing are not made explicit in the presentation of research and shared among the research community. This paper first outlines challenges experienced by researchers engaged in a large-scale coding project; then highlights valuable lessons learned; and finally discusses opportunities for further research on comparative case study analysis focusing on social-ecological systems and common pool resources. Includes supplemental materials and appendices published in the International Journal of the Commons 2016 Special Issue. Volume 10 - Issue 2 - 2016.

ContributorsRatajczyk, Elicia (Author) / Brady, Ute (Author) / Baggio, Jacopo (Author) / Barnett, Allain J. (Author) / Perez Ibarra, Irene (Author) / Rollins, Nathan (Author) / Rubinos, Cathy (Author) / Shin, Hoon Cheol (Author) / Yu, David (Author) / Aggarwal, Rimjhim (Author) / Anderies, John (Author) / Janssen, Marco (Author) / ASU-SFI Center for Biosocial Complex Systems (Contributor)
Created2016-09-09
Description

Governing common pool resources (CPR) in the face of disturbances such as globalization and climate change is challenging. The outcome of any CPR governance regime is the influenced by local combinations of social, institutional, and biophysical factors, as well as cross-scale interdependencies. In this study, we take a step towards

Governing common pool resources (CPR) in the face of disturbances such as globalization and climate change is challenging. The outcome of any CPR governance regime is the influenced by local combinations of social, institutional, and biophysical factors, as well as cross-scale interdependencies. In this study, we take a step towards understanding multiple-causation of CPR outcomes by analyzing 1) the co-occurrence of Design Principles (DP) by activity (irrigation, fishery and forestry), and 2) the combination(s) of DPs leading to social and ecological success. We analyzed 69 cases pertaining to three different activities: irrigation, fishery, and forestry. We find that the importance of the design principles is dependent upon the natural and hard human made infrastructure (i.e. canals, equipment, vessels etc.). For example, clearly defined social boundaries are important when the natural infrastructure is highly mobile (i.e. tuna fish), while monitoring is more important when the natural infrastructure is more static (i.e. forests or water contained within an irrigation system). However, we also find that congruence between local conditions and rules and proportionality between investment and extraction are key for CPR success independent from the natural and human hard made infrastructure. We further provide new visualization techniques for co-occurrence patterns and add to qualitative comparative analysis by introducing a reliability metric to deal with a large meta-analysis dataset on secondary data where information is missing or uncertain.

Includes supplemental materials and appendices publications in International Journal of the Commons 2016 Special Issue. Volume 10 - Issue 2 - 2016

ContributorsBaggio, Jacopo (Author) / Barnett, Alain J. (Author) / Perez, Irene (Author) / Brady, Ute (Author) / Ratajczyk, Elicia (Author) / Rollins, Nathan (Author) / Rubinos, Cathy (Author) / Shin, Hoon Cheol (Author) / Yu, David (Author) / Aggarwal, Rimjhim (Author) / Anderies, John (Author) / Janssen, Marco (Author) / Julie Ann Wrigley Global Institute of Sustainability (Contributor)
Created2016-09-09
128885-Thumbnail Image.png
Description

Investigation into the causes underlying the rapid, global amphibian decline provides critical insight into the effects of changing ecosystems. Hypothesized and confirmed links between amphibian declines, disease, and environmental changes are increasingly represented in published literature. However, there are few long-term amphibian studies that include data on population size, abnormality/injury

Investigation into the causes underlying the rapid, global amphibian decline provides critical insight into the effects of changing ecosystems. Hypothesized and confirmed links between amphibian declines, disease, and environmental changes are increasingly represented in published literature. However, there are few long-term amphibian studies that include data on population size, abnormality/injury rates, disease, and habitat variables to adequately assess changes through time. We cultured and identified microorganisms isolated from abnormal/injured and repressed tissue regeneration sites of the endangered Ozark Hellbender, Cryptobranchus alleganiensis bishopi, to discover potential causative agents responsible for their significant decline in health and population. This organism and our study site were chosen because the population and habitat of C. a. bishopi have been intensively studied from 1969–2009, and the abnormality/injury rate and apparent lack of regeneration were established.

Although many bacterial and fungal isolates recovered were common environmental organisms, several opportunistic pathogens were identified in association with only the injured tissues of C.a. bishopi. Bacterial isolates included Aeromonas hydrophila, a known amphibian pathogen, Granulicetella adiacens, Gordonai terrae, Stenotrophomonas maltophilia, Aerococcus viridans, Streptococcus pneumoniae and a variety of Pseudomonads, including Pseudomonas aeruginosa, P. stutzeri, and P. alcaligenes. Fungal isolates included species in the genera Penicillium, Acremonium, Cladosporium, Curvularia, Fusarium, Streptomycetes, and the Class Hyphomycetes. Many of the opportunistic pathogens identified are known to form biofilms. Lack of isolation of the same organism from all wounds suggests that the etiological agent responsible for the damage to C. a. bishopi may not be a single organism. To our knowledge, this is the first study to profile the external microbial consortia cultured from a Cryptobranchid salamander. The incidence of abnormalities/injury and retarded regeneration in C. a. bishopi may have many contributing factors including disease and habitat degradation. Results from this study may provide insight into other amphibian population declines.

Created2011-12-19
128863-Thumbnail Image.png
Description

The probiotic effects of Lactobacillus reuteri have been speculated to partly depend on its capacity to produce the antimicrobial substance reuterin during the reduction of glycerol in the gut. In this study, the potential of this process to protect human intestinal epithelial cells against infection with Salmonella enterica serovar Typhimurium

The probiotic effects of Lactobacillus reuteri have been speculated to partly depend on its capacity to produce the antimicrobial substance reuterin during the reduction of glycerol in the gut. In this study, the potential of this process to protect human intestinal epithelial cells against infection with Salmonella enterica serovar Typhimurium was investigated. We used a three-dimensional (3-D) organotypic model of human colonic epithelium that was previously validated and applied to study interactions between S. Typhimurium and the intestinal epithelium that lead to enteric salmonellosis. Using this model system, we show that L. reuteri protects the intestinal cells against the early stages of Salmonella infection and that this effect is significantly increased when L. reuteri is stimulated to produce reuterin from glycerol. More specifically, the reuterin-containing ferment of L. reuteri caused a reduction in Salmonella adherence and invasion (1 log unit), and intracellular survival (2 log units). In contrast, the L. reuteri ferment without reuterin stimulated growth of the intracellular Salmonella population with 1 log unit. The short-term exposure to reuterin or the reuterin-containing ferment had no observed negative impact on intestinal epithelial cell health. However, long-term exposure (24 h) induced a complete loss of cell-cell contact within the epithelial aggregates and compromised cell viability. Collectively, these results shed light on a potential role for reuterin in inhibiting Salmonella-induced intestinal infections and may support the combined application of glycerol and L. reuteri. While future in vitro and in vivo studies of reuterin on intestinal health should fine-tune our understanding of the mechanistic effects, in particular in the presence of a complex gut microbiota, this the first report of a reuterin effect on the enteric infection process in any mammalian cell type.

Created2012-05-31
128315-Thumbnail Image.png
Description

Many recent studies observe the increasing importance, influence, and analysis of resilience as a concept to understand the capacity of a system or individual to respond to change. The term has achieved prominence in diverse scientific fields, as well as public discourse and policy arenas. As a result, resilience has

Many recent studies observe the increasing importance, influence, and analysis of resilience as a concept to understand the capacity of a system or individual to respond to change. The term has achieved prominence in diverse scientific fields, as well as public discourse and policy arenas. As a result, resilience has been referred to as a boundary object or a bridging concept that is able to facilitate communication and understanding across disciplines, coordinate groups of actors or stakeholders, and build consensus around particular policy issues. We present a network analysis of bibliometric data to understand the extent to which resilience can be considered as a boundary object or a bridging concept in terms of its links across disciplines and scientific fields. We analyzed 994 papers and 35,952 citations between them to reveal the connectedness and links between and within fields. We analyzed the network according to different fields, modules, and sub-fields, showing a highly clustered citation network. Analyzing betweenness allowed us to identify how particular papers bridge across fields and how different fields are linked. With the exception of a few specific papers, most papers cite exclusively within their own field. We conclude that resilience is to an extent a boundary object because there are shared understandings across diverse disciplines and fields. However, it is more limited as a bridging concept because the citations across fields are concentrated among particular disciplines and papers, so the distinct fields do not widely or routinely refer to each other. There are some signs of resilience being used as an interdisciplinary concept to bridge scientific fields, particularly in social-ecological systems, which may itself constitute an emerging sub-field.

ContributorsBaggio, Jacopo (Author) / Brown, Katrina (Author) / Hellebrandt, Denis (Author) / ASU-SFI Center for Biosocial Complex Systems (Contributor)
Created2015