Matching Items (107)
Description
This study examined perception of K12 schooling systems as experienced by a randomsample of adults in Phoenix, AZ. It explored whether the values purported as key factors
in the American K12 schooling system - as presented in academic literature - were compatible with the lives, interests and goals of ‘users’, student-participants. In addition, it offered opportunity for post-K12 student-participants to share their views on the purposes, goals, and outcomes they held to be important. The sample consisted of 139 post-K12 stu-
dents/individuals residing in Phoenix, AZ. Mean age of student-participants was 29. Results indicated a mismatch between purported K12 schooling goals and important outcomes embedded in the system and values held by the K12 student-participants. The participants in this research generally perceived K12 schooling as valuable, both to themselves and to society at large, but stressed that the deficiencies they perceived in the system were particular to delivery platforms as they relate to the learning styles of students and belonging. Future life skills and success - in and after K12 schooling - whether related to college or not were also of importance. Results revealed that the initial hypothesis of income, age, and ethnicity as
key factors in satisfaction with K12 schooling was not borne-out. Rather it revealed that a sense of belonging and the suitability of learning platforms to the individual learning styles of students were of greatest significance.
ContributorsParker-Anderies, Margaret (Author) / Janssen, Marco (Thesis advisor) / Garcia, David (Committee member) / Mishra, Punya (Committee member) / Arizona State University (Publisher)
Created2022
Description
Scientists are entrusted with developing novel molecular strategies for effective prophylactic and therapeutic interventions. Antivirals are indispensable tools that can be targeted at viral domains directly or at cellular domains indirectly to obstruct viral infections and reduce pathogenicity. Despite their transformative potential in healthcare, to date, antivirals have been clinically approved to treat only 10 out of the greater than 200 known pathogenic human viruses. Additionally, as obligate intracellular parasites, many virus functions are intimately coupled with host cellular processes. As such, the development of a clinically relevant antiviral is challenged by the limited number of clear targets per virus and necessitates an extensive insight into these molecular processes. Compounding this challenge, many viral pathogens have evolved to evade effective antivirals. Therefore, a means to develop virus- or strain-specific antivirals without detailed insight into each idiosyncratic biochemical mechanism may aid in the development of antivirals against a larger swath of pathogens. Such an approach will tremendously benefit from having the specific molecular recognition of viral species as the lowest barrier. Here, I modify a nanobody (anti-green fluorescent protein) that specifically recognizes non-essential epitopes (glycoprotein M-pHluorin chimera) presented on the extra virion surface of a virus (Pseudorabies virus strain 486). The nanobody switches from having no inhibitory properties (tested up to 50 μM) to ∼3 nM IC50 in in vitro infectivity assays using porcine kidney (PK15) cells. The nanobody modifications use highly reliable bioconjugation to a three-dimensional wireframe deoxyribonucleic acid (DNA) origami scaffold. Mechanistic studies suggest that inhibition is mediated by the DNA origami scaffold bound to the virus particle, which obstructs the internalization of the viruses into cells, and that inhibition is enhanced by avidity resulting from multivalent virus and scaffold interactions. The assembled nanostructures demonstrate negligible cytotoxicity (<10 nM) and sufficient stability, further supporting their therapeutic potential. If translatable to other viral species and epitopes, this approach may open a new strategy that leverages existing infrastructures – monoclonal antibody development, phage display, and in vitro evolution - for rapidly developing novel antivirals in vivo.
ContributorsPradhan, Swechchha (Author) / Hariadi, Rizal (Thesis advisor) / Hogue, Ian (Committee member) / Varsani, Arvind (Committee member) / Chen, Qiang (Committee member) / Arizona State University (Publisher)
Created2022
Description
Monkeypox virus (MPXV) is an orthopoxvirus that causes smallpox-like disease and has up to a 10% mortality rate, depending on the infectious strain. The global eradication of the smallpox virus has led to the decrease in smallpox vaccinations, which has led to a drastic increase in the number of human MPXV cases. MPXV has been named the most important orthopoxvirus to infect humans since the eradication of smallpox and has been the causative agent of the 2022 world-wide MPXV outbreak. Despite being highly pathogenic, MPXV contains a natural truncation at the N-terminus of its E3 homologue. Vaccinia virus (VACV) E3 protein has two domains: an N- terminus Z-form nucleic acid binding domain (Z-BD) and a C-terminus double stranded RNA binding domain (dsRBD). Both domains are required for pathogenesis, interferon (IFN) resistance, and protein kinase R (PKR) inhibition. The N-terminus is required for evasion of Z-DNA binding protein 1 (ZBP1)-dependent necroptosis. ZBP1 binding to Z- form deoxyribonucleic acid/ribonucleic acid (Z-DNA/RNA) leads to activation of receptor-interacting protein kinase 3 (RIPK3) leading to mixed lineage kinase domain- like (MLKL) phosphorylation, aggregation and cell death. This study investigated how different cell lines combat MPXV infection and how MPXV has evolved ways to circumvent the host response. MPXV is shown to inhibit necroptosis in L929 cells by degrading RIPK3 through the viral inducer of RIPK3 degradation (vIRD) and by inhibiting MLKL aggregation. Additionally, the data shows that IFN treatment efficiently inhibits MPXV replication in a ZBP1-, RIPK3-, and MLKL- dependent manner, but independent of necroptosis. Also, the data suggests that an IFN inducer with a pancaspase or proteasome inhibitor could potentially be a beneficial treatment against MPXV infections. Furthermore, it reveals a link between PKR and pathogen-induced necroptosis that has not been previously described.
ContributorsWilliams, Jacqueline (Author) / Jacobs, Bertram (Thesis advisor) / Langland, Jeffrey (Committee member) / Lake, Douglas (Committee member) / Varsani, Arvind (Committee member) / Arizona State University (Publisher)
Created2022
Description
Traditional public health strategies for assessing human behavior, exposure, and activity are considered resource-exhaustive, time-consuming, and expensive, warranting a need for alternative methods to enhance data acquisition and subsequent interventions. This dissertation critically evaluated the use of wastewater-based epidemiology (WBE) as an inclusive and non-invasive tool for conducting near real-time population health assessments. A rigorous literature review was performed to gauge the current landscape of WBE to monitor for biomarkers indicative of diet, as well as exposure to estrogen-mimicking endocrine disrupting (EED) chemicals via route of ingestion. Wastewater-derived measurements of phytoestrogens from August 2017 through July 2019 (n = 156 samples) in a small sewer catchment revealed seasonal patterns, with highest average per capita consumption rates in January through March of each year (2018: 7.0 ± 2.0 mg d-1; 2019: 8.2 ± 2.3 mg d-1) and statistically significant differences (p = 0.01) between fall and winter (3.4 ± 1.2 vs. 6.1 ± 2.9 mg d-1; p ≤ 0.01) and spring and summer (5.6 ± 2.1 vs. 3.4 ± 1.5 mg d-1; p ≤ 0.01). Additional investigations, including a human gut microbial composition analysis of community wastewater, were performed to support a methodological framework for future implementation of WBE to assess population-level dietary behavior. In response to the COVID-19 global pandemic, a high-frequency, high-resolution sample collection approach with public data sharing was implemented throughout the City of Tempe, Arizona, and analyzed for SARS-CoV-2 (E gene) from April 2020 through March 2021 (n = 1,556 samples). Results indicate early warning capability during the first wave (June 2020) compared to newly reported clinical cases (8.5 ± 2.1 days), later transitioning to a slight lagging indicator in December/January 2020-21 (-2.0 ± 1.4 days). A viral hotspot from within a larger catchment area was detected, prompting targeted interventions to successfully mitigate community spread; reinforcing the importance of sample collection within the sewer infrastructure. I conclude that by working in tandem with traditional approaches, WBE can enlighten a comprehensive understanding of population health, with methods and strategies implemented in this work recommended for future expansion to produce timely, actionable data in support of public health.
ContributorsBowes, Devin Ashley (Author) / Halden, Rolf U (Thesis advisor) / Krajmalnik-Brown, Rosa (Thesis advisor) / Conroy-Ben, Otakuye (Committee member) / Varsani, Arvind (Committee member) / Whisner, Corrie (Committee member) / Arizona State University (Publisher)
Created2022
Description
The consumption of food, energy, and water (FEW) resources in U.S. households is very carbon-intensive. However, these negative climate change impacts are often invisible due to insufficient awareness and knowledge. Serious games (SGs) can potentially address this issue through an experiential and rigorous approach to simulate household actions and impacts in a playful but realistic setting. This dissertation focuses on: (a) the design and testing of an SG called HomeRUN (Role-play for Understanding Nexus); (b) the effectiveness of gameplay in advancing player knowledge about the upfront costs, financial returns, and greenhouse gas (GHG) emissions of various household decisions; and (c) the effectiveness of intervention messages in increasing FEW conservation to reduce household GHG emissions. The results of gameplay sessions played by 150 university students show that HomeRUN is fun to play, creates a flow experience, and results in experiential learning. The majority of players agreed that the game experience will continue over time to influence their future consumption behaviors to conserve FEW resources. Female players tended to gain more knowledge about financial aspects of interventions, whereas male players were more likely to increase their understandings of GHG emissions and resource consumption after playing HomeRUN. Social comparison intervention messages about energy and food consumption led to the highest reductions in household carbon emissions. The messages associated with each FEW resource tended to be most likely to lead to FEW conservation actions with the game that most closely corresponded to the particular FEW resource addressed in the message. This dissertation advances understandings about the design and use of SGs to foster learning and promote sustainable household FEW consumption.
ContributorsHanif, Muhammad Adnan (Author) / Agusdinata, Datu Buyung (Thesis advisor) / Halvorsen, Kathleen (Committee member) / Janssen, Marco (Committee member) / Arizona State University (Publisher)
Created2021
Description
Poxviruses such as monkeypox virus (MPXV) are emerging zoonotic diseases. Compared to MPXV, Vaccinia virus (VACV) has reduced pathogenicity in humans and can be used as a partially protective vaccine against MPXV. While most orthopoxviruses have E3 protein homologues with highly similar N-termini, the MPXV homologue, F3, has a start codon mutation leading to an N-terminal truncation of 37 amino acids. The VACV protein E3 consists of a dsRNA binding domain in its C-terminus which must be intact for pathogenicity in murine models and replication in cultured cells. The N-terminus of E3 contains a Z-form nucleic acid (ZNA) binding domain and is also required for pathogenicity in murine models. Poxviruses produce RNA transcripts that extend beyond the transcribed gene which can form double-stranded RNA (dsRNA). The innate immune system easily recognizes dsRNA through proteins such as protein kinase R (PKR). After comparing a vaccinia virus with a wild-type E3 protein (VACV WT) to one with an E3 N-terminal truncation of 37 amino acids (VACV E3Δ37N), phenotypic differences appeared in several cell lines. In HeLa cells and certain murine embryonic fibroblasts (MEFs), dsRNA recognition pathways such as PKR become activated during VACV E3Δ37N infections, unlike VACV WT. However, MPXV does not activate PKR in HeLa or MEF cells. Additional investigation determined that MPXV produces less dsRNA than VACV. VACV E3Δ37N was made more similar to MPXV by selecting mutants that produce less dsRNA. By producing less dsRNA, VACV E3Δ37N no longer activated PKR in HeLa or MEF cells, thus restoring the wild-type phenotype. Furthermore, in other cell lines such as L929 (also a murine fibroblast) VACV E3Δ37N, but not VACV WT infection leads to activation of DNA-dependent activator of IFN-regulatory factors (DAI) and induction of necroptotic cell death. The same low dsRNA mutants demonstrate that DAI activation and necroptotic induction is independent of classical dsRNA. Finally, investigations of spread in an animal model and replication in cell lines where both the PKR and DAI pathways are intact determined that inhibition of both pathways is required for VACV E3Δ37N to replicate.
ContributorsCotsmire, Samantha (Author) / Jacobs, Bertram L (Thesis advisor) / Varsani, Arvind (Committee member) / Hogue, Brenda (Committee member) / Haydel, Shelley (Committee member) / Arizona State University (Publisher)
Created2021
Description
Bats are a highly diverse mammal species with a dense virome and fascinating immune system. The following project utilizes metagenomics in order to identify DNA viruses present in populations of silver-haired bats and Mexican free-tailed bats from southern Arizona. A significant number of DNA viruses and novel viruses were identified in the Cressdnaviricota phylum and Microvirdae family.
ContributorsHarding, Ciara (Author) / Varsani, Arvind (Thesis director) / Dolby, Greer (Committee member) / Kraberger, Simona (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor) / Watts College of Public Service & Community Solut (Contributor)
Created2022-05
Description
Copper demand is surging in the U.S. and around the world as countries embrace new forms of energy to combat climate change. But copper mining – while a key strategy to address supply shortages – can serve as a vehicle for injustice by imposing socio-ecological burdens for nearby communities. Due to the growing demand for copper with resulting justice issues, more research is needed to evaluate governance for the mining sector using an environmental justice lens. The National Environmental Policy Act (NEPA) is a key environmental regulation that governs mining in the U.S. Therefore, I used a qualitative case study approach to examine how NEPA requirements shape engagement in public comment opportunities. I selected the Resolution Copper Mine as a case study because of its potential to support the energy transition but pose a significant dilemma for justice: the mine is anticipated to generate 25 percent of the U.S. copper demand each year but disturb lands that hold spiritual significance for Native American Tribes. I used the Institutional Analysis and Development (IAD) framework to analyze institutional dynamics and evaluate the NEPA process for public participation using a procedural justice lens. Drawing on interview data and document analysis, the results show that process rules such as a land exchange bill and the lengths of comment opportunities were among the key barriers for participation. Socioeconomic conditions of communities including access to social resources (i.e. access to internet and technical assistance) and institutional trust posed further barriers for participation. Hence, this study suggests that federal decision-makers should aim to better integrate procedural justice into the NEPA process.
ContributorsLewis, Sydney (Author) / Kellner, Elke (Thesis director) / Janssen, Marco (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2024-05
Description
Wild horses have roamed the Salt River in Mesa, Arizona since the early 1800s and contribute to the great diversity of the region. Conservation of the herd has been a primary focus for many years and a current focus is population stabilization, but little is known about their virome. Circoviridae, Genomoviridae, and Smacoviridae are the three Cressdnaviricota viruses that have been identified in horses to date. Smacoviridae is classified by the rolling circle replication-associated proteins (Rep) and has a small (2.3-2.9kb), circular, single-stranded genome. The goal of this study was to identify DNA viruses within the fecal samples of the Salt River horses. Samples were collected along the lower Salt River and analyzed in the lab using a metagenomics approach. There were 422 full novel genomes of smacoviruses detected across all samples that were grouped into 144 species based on the similarity of the pairwise identity. Phylogenetic analysis shows the smacoviruses from this study fall into 3 classified genera and the rest cluster into 11 new clades. These results expand the viral diversity associated with wild horses and Smacoviridae, and further studies are needed to determine the host of these viruses.
ContributorsMcGraw, Hannah (Author) / Varsani, Arvind (Thesis director) / Murphree, Julie (Committee member) / Kraberger, Simona (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2024-05
Description
Scorpions are predatory arachnids that are among the most ancient terrestrial invertebrates. They are typically found residing in desert and riparian environments. Viruses associated with scorpions have been explored in the past, unveiling partial RNA virus sequences and polyomaviruses, but more research in this area is necessary. Cycloviruses are non-enveloped viruses with circular single-stranded DNA genomes (~1.7 to 1.9 kb). Cycloviruses were initially identified in mammals and have now been detected in samples from a wide range of mammalian and insect species. Polyomaviruses are double-stranded DNA viruses (~4 to 7 kb). They are known for causing tumors in the host it infects, and have previously been identified in a diverse array of organisms, including scorpions. The objective for this study was to identify known and novel viruses in scorpions. Using high-throughput sequencing and traditional molecular techniques we determine the genome sequences of cycloviruses and polyomaviruses. Sixteen of the forty-three scorpion samples were positive for eight different species of cycloviruses. According to ICTV guidelines, seven of the eight species were novel cycloviruses which were found in bark scorpions, stripe-tailed scorpions, yellow ground scorpions, and giant hairy scorpions (Centruroides sculpturatus, Paravaejovis spinigerus, Paravaejovis confusus & Hadrurus arizonensis) from Maricopa, Pinal, and Pima county in Arizona, USA. Additionally, one previously known cyclovirus species was recovered in bark scorpions (Centruroides sculpturatus) in Pima county which had previously been documented in guano from a Mexican free-tailed bat in Arizona. There were ten scorpions out of forty-three for which we recovered polyomavirus scorpion samples that grouped into four different polyomavirus species. Polyomaviruses were only identified in bark scorpions (Centruroides sculpturatus) from Maricopa, Pinal, and Pima county. Of the polyomavirus genomes recovered three belong to previously identified scorpion polyomavirus 1 and five to scorpion polyomavirus 3, and two represent two new species named scorpion polyomavirus 4 and scorpion polyomavirus 5. The implications of the discovery of cycloviruses and polyomaviruses from this study contributes to our understanding of viral diversity associated with Scorpions.
ContributorsGomez, Magali (Author) / Neil, Julia (Co-author) / Varsani, Arvind (Thesis director) / Kraberger, Simona (Committee member) / Barrett, The Honors College (Contributor) / School of International Letters and Cultures (Contributor) / School of Life Sciences (Contributor)
Created2024-05