Matching Items (43)
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DescriptionA
ContributorsLund, Michael (Author) / Varsani, Arvind (Thesis advisor) / Upham, Nathan (Committee member) / Harris, Robin (Committee member) / Arizona State University (Publisher)
Created2023
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Description
The human gut microbiome is associated with health outcomes including gastrointestinal and metabolic health, autoimmune disease and cancer. However, the role of the microbiome in many disease processes, including in the preterm gastrointestinal tract and female genital tract, has yet to be defined. Further, the diverse community of viruses within

The human gut microbiome is associated with health outcomes including gastrointestinal and metabolic health, autoimmune disease and cancer. However, the role of the microbiome in many disease processes, including in the preterm gastrointestinal tract and female genital tract, has yet to be defined. Further, the diverse community of viruses within the microbiome (the virome) is understudied compared to bacteria. Here, I examine the microbiome and virome in specific disease models that are poorly understood: necrotizing enterocolitis (NEC), discordant HIV shedding in women living with HIV (WHLIV), female genital tract inflammation and gammaherpesvirus infection. Specifically, I examined the gut virome longitudinally in a cohort of preterm infants at risk for NEC; the female genital tract (FGT) microbiome and virome longitudinally in a cohort of WLHIV from Lima, Peru; the FGT virome in women from Phoenix, Arizona with differing levels of genital inflammation and different microbiome compositions; and the gut microbiome in murine gammaherpesvirus 68 (MHV68) infection. Further, I contributed to research responding to the spread of SARS-CoV-2 in Arizona. I found that 1) gut virome beta diversity decreased before NEC onset in preterm infants, suggesting a role for the virome in NEC; 2) FGT microbiome instability was associated with discordant HIV shedding, while FGT virome composition changed in association with ART duration and immune recovery; 3) FGT virome composition was associated with inflammation and microbiome composition; and 4) MHV68 infection outcomes were independent of microbiome perturbation, which may reflect environmental influences. The results of this research advance understanding of the microbiome and virome in these specific disease processes, and support further investigation of the microbiome and virome in preterm infant gastrointestinal health and FGT health, as well as environmental effects in microbiome research.
ContributorsKaelin, Emily (Author) / Lim, Efrem (Thesis advisor) / Varsani, Arvind (Committee member) / Jacobs, Bertram (Committee member) / McFadden, Grant (Committee member) / Rahman, Masmudur (Committee member) / Arizona State University (Publisher)
Created2024
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Description
Arachnids belong to the phylum Arthropoda, the largest phylum in the animal kingdom. Ticks are blood-feeding arachnids that vector numerous pathogens of significant medical and veterinary importance, while scorpions have become a common concern in urban desert cities due to the high level of toxicity in their venom. To date,

Arachnids belong to the phylum Arthropoda, the largest phylum in the animal kingdom. Ticks are blood-feeding arachnids that vector numerous pathogens of significant medical and veterinary importance, while scorpions have become a common concern in urban desert cities due to the high level of toxicity in their venom. To date, viruses associated with arachnids have been under sampled and understudied. Here viral metagenomics was used to explore the diversity of viruses present in ticks and scorpions. American dog ticks (Dermacentor variabilis) and blacklegged ticks (Ixodes scapularis) were collected in Pennsylvania while one hairy scorpion (Hadrurus arizonensis) and four bark scorpions (Centruroides sculpturatus) were collected in Phoenix. Novel viral genomes described here belong to the families Polyomaviridae, Anelloviridae, Genomoviridae, and a newly proposed family, Arthropolviridae.

Polyomaviruses are non-enveloped viruses with a small, circular double-stranded DNA (dsDNA) genomes that have been identified in a variety of mammals, birds and fish and are known to cause various diseases. Arthropolviridae is a proposed family of circular, large tumor antigen encoding dsDNA viruses that have a unidirectional genome organization. Genomoviruses and anelloviruses are ssDNA viruses that have circular genomes ranging in size from 2–2.4 kb and 2.1–3.8 kb, respectively. Genomoviruses are ubiquitous in the environment, having been identified in a wide range of animal, plant and environmental samples, while anelloviruses have been associated with a plethora of animals.

Here, 16 novel viruses are reported that span four viral families. Eight novel polyomaviruses were recovered from bark scorpions, three arthropolviruses were recovered from dog ticks and one arthropolvirus from a hairy scorpion. Viruses belonging to the families Polyomaviridae and Arthropolviridae are highly divergent. This is the first more extensive study of these viruses in arachnids. Three genomoviruses were recovered from both dog and deer ticks and one anellovirus was recovered from deer ticks, which are the first records of these viruses being recovered from ticks. This work highlights the diversity of dsDNA and ssDNA viruses in the arachnid population and emphasizes the importance of performing viral surveys on these populations.
ContributorsSchmidlin, Kara (Author) / Varsani, Arvind (Thesis advisor) / Van Doorslaer, Koenraad (Committee member) / Stenglein, Mark (Committee member) / Arizona State University (Publisher)
Created2019
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Description
One of the single-most insightful, and visionary talks of the 20th century, “There’s plenty of room at the bottom,” by Dr. Richard Feynman, represented a first foray into the micro- and nano-worlds of biology and chemistry with the intention of direct manipulation of their individual components. Even so, for decades

One of the single-most insightful, and visionary talks of the 20th century, “There’s plenty of room at the bottom,” by Dr. Richard Feynman, represented a first foray into the micro- and nano-worlds of biology and chemistry with the intention of direct manipulation of their individual components. Even so, for decades there has existed a gulf between the bottom-up molecular worlds of biology and chemistry, and the top-down world of nanofabrication. Creating single molecule nanoarrays at the limit of diffraction could incentivize a paradigm shift for experimental assays. However, such arrays have been nearly impossible to fabricate since current nanofabrication tools lack the resolution required for precise single-molecule spatial manipulation. What if there existed a molecule which could act as a bridge between these top-down and bottom-up worlds?

At ~100-nm, a DNA origami macromolecule represents one such bridge, acting as a breadboard for the decoration of single molecules with 3-5 nm resolution. It relies on the programmed self-assembly of a long, scaffold strand into arbitrary 2D or 3D structures guided via approximately two hundred, short, staple strands. Once synthesized, this nanostructure falls in the spatial manipulation regime of a nanofabrication tool such as electron-beam lithography (EBL), facilitating its high efficiency immobilization in predetermined binding sites on an experimentally relevant substrate. This placement technology, however, is expensive and requires specialized training, thereby limiting accessibility.

The work described here introduces a method for bench-top, cleanroom/lithography-free, DNA origami placement in meso-to-macro-scale grids using tunable colloidal nanosphere masks, and organosilane-based surface chemistry modification. Bench-top DNA origami placement is the first demonstration of its kind which facilitates precision placement of single molecules with high efficiency in diffraction-limited sites at a cost of $1/chip. The comprehensive characterization of this technique, and its application as a robust platform for high-throughput biophysics and digital counting of biomarkers through enzyme-free amplification are elucidated here. Furthermore, this technique can serve as a template for the bottom-up fabrication of invaluable biophysical tools such as zero mode waveguides, making them significantly cheaper and more accessible to the scientific community. This platform has the potential to democratize high-throughput single molecule experiments in laboratories worldwide.
ContributorsShetty, Rishabh Manoj (Author) / Hariadi, Rizal F (Thesis advisor) / Gopinath, Ashwin (Committee member) / Varsani, Arvind (Committee member) / Nikkhah, Mehdi (Committee member) / Tillery, Stephen H (Committee member) / Hu, Ye (Committee member) / Arizona State University (Publisher)
Created2019
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Description
The human papillomavirus (HPV) is a double-stranded DNA virus responsible for causing upwards of 80% of head and neck cancers in the oropharyngeal region. Current treatments, including surgery, chemotherapy, and/or radiation, are aggressive and elicit toxic effects. HPV is a pathogen that expresses viral-specific oncogenic proteins that play a role

The human papillomavirus (HPV) is a double-stranded DNA virus responsible for causing upwards of 80% of head and neck cancers in the oropharyngeal region. Current treatments, including surgery, chemotherapy, and/or radiation, are aggressive and elicit toxic effects. HPV is a pathogen that expresses viral-specific oncogenic proteins that play a role in cancer progression. These proteins may serve as potential targets for immunotherapeutic applications. Engineered T cell receptor (TCR) therapy may be an advantageous approach for HPV-associated cancers. In TCR therapy, TCRs are modified to express a receptor that is specific to an immunogenic antigen (part of the virus/cancer capable of eliciting an immune response). Since HPV-associated oropharyngeal cancers typically express unique viral proteins, it is important to identify the TCRs capable of recognizing these proteins. Evidence supports that head and neck cancers typically experience high levels of immune cell infiltration and are subsequently associated with increased survival rates. Most of the immune cell infiltrations in HPV+ HNSCC are CD8+ T lymphocytes, drawing attention to their prospective use in cellular immunotherapies. While TCRs are highly specific, the TCR repertoire is extremely diverse; enabling the immune system to fight off numerous pathogens. In project 1, I review approaches to analyzing TCR diversity and explore the use of DNA origami in retrieving paired TCR sequences from a population. The results determine that DNA origami can be used within a monoclonal population but requires further optimization before being applied in a polyclonal setting. In project 2, I investigate HPV-specific T-cell dysfunction; I detect low frequency HPV-specific CD8+ T cells, determine that they are tumor specific, and show that HPV+HNSCC patients exhibit increased epitope-specific levels of CD8+T cell exhaustion. In project 3, I apply methods to expand and isolate TCRαβ sequences derived from donors stimulated with a previously identified HPV epitope. Single-cell analysis provide ten unique TCRαβ pairs with corresponding CDR3 sequences that may serve as therapeutic candidates. This thesis contributes to fundamental immunology by contributing to the knowledge of T cell dysfunction within HPV+HNSCC and further reveals TCR gene usage within an HPV stimulated population, thus identifying potential TCR pairs for adoptive cell therapies.
ContributorsUlrich, Peaches Rebecca (Author) / Anderson, Karen S (Thesis advisor) / Lake, Douglas (Committee member) / Maley, Carlo (Committee member) / Varsani, Arvind (Committee member) / Arizona State University (Publisher)
Created2020
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Description
Viruses infect organisms in all domains of life and are abundant entities in ecosystems. In particular, single-stranded DNA viruses have been found in a wide variety of hosts and ecosystems. Using a metagenomic approach, novel circular viruses have been identified in multiple environmental samples. This thesis focuses on viruses and

Viruses infect organisms in all domains of life and are abundant entities in ecosystems. In particular, single-stranded DNA viruses have been found in a wide variety of hosts and ecosystems. Using a metagenomic approach, novel circular viruses have been identified in multiple environmental samples. This thesis focuses on viruses and virus dynamics from avian sources. As part of this thesis, a novel phapecoctavirus was identified in a pigeon cloacal swab. The phapecoctavirus is most closely related to Klebsiella phage ZCKP1, identified from a freshwater sample. Beyond this, this thesis addresses circoviruses, which are of interest due to disease they cause to avian species. Evolution of circovirus recombination was studied in a closed system of uninfected and infected pigeons. 178 genomes of pigeon circovirus were sequenced, and patterns of recombination determined. Seven genotypes were present in the population and genotype 4 was shown to be present in a majority of samples after the experiment was finished. Circoviruses were also identified in waterfowl feces and the ten genomes recovered represent two new circovirus species. Overall, the research described in this thesis helped to gain a deeper understanding of the diversity and evolution of circular DNA viruses associated with avian species.
ContributorsKhalifeh, Anthony (Author) / Varsani, Arvind (Thesis advisor) / Kraberger, Simona J (Committee member) / Dolby, Greer (Committee member) / Arizona State University (Publisher)
Created2021
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Description
The family Cactaceae is extremely diverse and has a near global distribution yet very little has been described regarding the community of viruses that infect or are associated with cacti. This research characterizes the diversity of viruses associated with Cactaceae plants and their evolutionary aspects. Five viruses belonging to the

The family Cactaceae is extremely diverse and has a near global distribution yet very little has been described regarding the community of viruses that infect or are associated with cacti. This research characterizes the diversity of viruses associated with Cactaceae plants and their evolutionary aspects. Five viruses belonging to the economically relevant plant virus family Geminiviridae were identified, initially, two novel divergent geminiviruses named Opuntia virus 1 (OpV1) and Opuntia virus 2 (OpV2) and Opuntia becurtovirus, a new strain within the genus Becurtovirus. These three viruses were also found in co-infection. In addition, two known geminiviruses, the squash leaf curl virus (SLCV) and watermelon chlorotic stunt virus (WCSV) were identified infecting Cactaceae plants and other non-cactus plants in the USA and Mexico. Both SLCV and WCSV are known to cause severe disease in cultivated Cucurbitaceae plants in the USA and Middle East, respectively. This study shows that WCSV was introduced in the America two times, and it is the first identification of this virus in the USA, demonstrating is likely more widespread in North America. These findings along with the Opuntia becurtovirus are probable events of spill-over in agro-ecological interfaces. A novel circular DNA possibly bipartite plant-infecting virus that encodes protein similar to those of geminiviruses was also identified in an Opuntia discolor plant in Brazil, named utkilio virus, but it is evolutionary distinct likely belonging to a new taxon. Viruses belonging to the ssDNA viral family Genomoviridae are also described and those thus far been associated with fungi hosts, so it is likely the ones identified in plants are associated with their phytobiome. Overall, the results of this project provide a molecular and biological characterization of novel geminiviruses and genomoviruses associated with cacti as well as demonstrate the impact of agro-ecological interfaces in the spread of viruses from or to native plants. It also highlights the importance of viral metagenomics studies in exploring virus diversity and evolution given then amount of virus diversity identified. This is important for conservation and management of cacti in a global scale, including the relevance of controlled movement of plants within countries.
ContributorsSalgado Fontenele, Rafaela (Author) / Varsani, Arvind (Thesis advisor) / Wilson, Melissa (Committee member) / Majure, Lucas (Committee member) / Van Doorslaer, Koenraad (Committee member) / Wojciechowski, Martin (Committee member) / Arizona State University (Publisher)
Created2021
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Description

Deposits of dark material appear on Vesta’s surface as features of relatively low-albedo in the visible wavelength range of Dawn’s camera and spectrometer. Mixed with the regolith and partially excavated by younger impacts, the material is exposed as individual layered outcrops in crater walls or ejecta patches, having been uncovered

Deposits of dark material appear on Vesta’s surface as features of relatively low-albedo in the visible wavelength range of Dawn’s camera and spectrometer. Mixed with the regolith and partially excavated by younger impacts, the material is exposed as individual layered outcrops in crater walls or ejecta patches, having been uncovered and broken up by the impact. Dark fans on crater walls and dark deposits on crater floors are the result of gravity-driven mass wasting triggered by steep slopes and impact seismicity. The fact that dark material is mixed with impact ejecta indicates that it has been processed together with the ejected material. Some small craters display continuous dark ejecta similar to lunar dark-halo impact craters, indicating that the impact excavated the material from beneath a higher-albedo surface. The asymmetric distribution of dark material in impact craters and ejecta suggests non-continuous distribution in the local subsurface. Some positive-relief dark edifices appear to be impact-sculpted hills with dark material distributed over the hill slopes.

Dark features inside and outside of craters are in some places arranged as linear outcrops along scarps or as dark streaks perpendicular to the local topography. The spectral characteristics of the dark material resemble that of Vesta’s regolith. Dark material is distributed unevenly across Vesta’s surface with clusters of all types of dark material exposures. On a local scale, some craters expose or are associated with dark material, while others in the immediate vicinity do not show evidence for dark material. While the variety of surface exposures of dark material and their different geological correlations with surface features, as well as their uneven distribution, indicate a globally inhomogeneous distribution in the subsurface, the dark material seems to be correlated with the rim and ejecta of the older Veneneia south polar basin structure. The origin of the dark material is still being debated, however, the geological analysis suggests that it is exogenic, from carbon-rich low-velocity impactors, rather than endogenic, from freshly exposed mafic material or melt, exposed or created by impacts.

ContributorsJaumann, R. (Author) / Nass, A. (Author) / Otto, K. (Author) / Krohn, K. (Author) / Stephan, K. (Author) / McCord, T. B. (Author) / Williams, David (Author) / Raymond, C. A. (Author) / Blewett, D. T. (Author) / Hiesinger, H. (Author) / Yingst, R. A. (Author) / De Sanctis, M. C. (Author) / Palomba, E. (Author) / Roatsch, T. (Author) / Matz, K-D. (Author) / Preusker, F. (Author) / Scholten, F. (Author) / Russell, C. T. (Author) / College of Liberal Arts and Sciences (Contributor)
Created2014-09-15
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Description

We produced a geologic map of the Av-9 Numisia quadrangle of asteroid Vesta using Dawn spacecraft data to serve as a tool to understand the geologic relations of surface features in this region. These features include the plateau Vestalia Terra, a hill named Brumalia Tholus, and an unusual “dark ribbon”

We produced a geologic map of the Av-9 Numisia quadrangle of asteroid Vesta using Dawn spacecraft data to serve as a tool to understand the geologic relations of surface features in this region. These features include the plateau Vestalia Terra, a hill named Brumalia Tholus, and an unusual “dark ribbon” material crossing the majority of the map area. Stratigraphic relations suggest that Vestalia Terra is one of the oldest features on Vesta, despite a model crater age date similar to that of much of the surface of the asteroid. Cornelia, Numisia and Drusilla craters reveal bright and dark material in their walls, and both Cornelia and Numisia have smooth and pitted terrains on their floors suggestive of the release of volatiles during or shortly after the impacts that formed these craters. Cornelia, Fabia and Teia craters have extensive bright ejecta lobes. While diogenitic material has been identified in association with the bright Teia and Fabia ejecta, hydroxyl has been detected in the dark material within Cornelia, Numisia and Drusilla. Three large pit crater chains appear in the map area, with an orientation similar to the equatorial troughs that cut the majority of Vesta. Analysis of these features has led to several interpretations of the geological history of the region. Vestalia Terra appears to be mechanically stronger than the rest of Vesta. Brumalia Tholus may be the surface representation of a dike-fed laccolith. The dark ribbon feature is proposed to represent a long-runout ejecta flow from Drusilla crater.

ContributorsBuczkowski, D. L. (Author) / Wyrick, D.Y. (Author) / Toplis, M. (Author) / Yingst, R. A. (Author) / Williams, David (Author) / Garry, W. B. (Author) / Mest, S. (Author) / Kneissl, T. (Author) / Scully, J. E. C. (Author) / Nathues, A. (Author) / De Sanctis, M. C. (Author) / Le Corre, L. (Author) / Reddy, V. (Author) / Hoffmann, M. (Author) / Ammannito, E. (Author) / Frigeri, A. (Author) / Tosi, F. (Author) / Preusker, F. (Author) / Roatsch, T. (Author) / Raymond, C. A. (Author) / Jaumann, R. (Author) / Pieters, C. M. (Author) / Russell, C. T. (Author) / College of Liberal Arts and Sciences (Contributor)
Created2014-03-14
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Description

Vesta is a unique, intermediate class of rocky body in the Solar System, between terrestrial planets and small asteroids, because of its size (average radius of ∼263 km) and differentiation, with a crust, mantle and core. Vesta’s low surface gravity (0.25 m/s2) has led to the continual absence of a

Vesta is a unique, intermediate class of rocky body in the Solar System, between terrestrial planets and small asteroids, because of its size (average radius of ∼263 km) and differentiation, with a crust, mantle and core. Vesta’s low surface gravity (0.25 m/s2) has led to the continual absence of a protective atmosphere and consequently impact cratering and impact-related processes are prevalent. Previous work has shown that the formation of the Rheasilvia impact basin induced the equatorial Divalia Fossae, whereas the formation of the Veneneia impact basin induced the northern Saturnalia Fossae. Expanding upon this earlier work, we conducted photogeologic mapping of the Saturnalia Fossae, adjacent structures and geomorphic units in two of Vesta’s northern quadrangles: Caparronia and Domitia. Our work indicates that impact processes created and/or modified all mapped structures and geomorphic units. The mapped units, ordered from oldest to youngest age based mainly on cross-cutting relationships, are: (1) Vestalia Terra unit, (2) cratered highlands unit, (3) Saturnalia Fossae trough unit, (4) Saturnalia Fossae cratered unit, (5) undifferentiated ejecta unit, (6) dark lobate unit, (7) dark crater ray unit and (8) lobate crater unit. The Saturnalia Fossae consist of five separate structures: Saturnalia Fossa A is the largest (maximum width of ∼43 km) and is interpreted as a graben, whereas Saturnalia Fossa B-E are smaller (maximum width of ∼15 km) and are interpreted as half grabens formed by synthetic faults. Smaller, second-order structures (maximum width of <1 km) are distinguished from the Saturnalia Fossae, a first-order structure, by the use of the general descriptive term ‘adjacent structures’, which encompasses minor ridges, grooves and crater chains. For classification purposes, the general descriptive term ‘minor ridges’ characterizes ridges that are not part of the Saturnalia Fossae and are an order of magnitude smaller (maximum width of <1 km vs. maximum width of ∼43 km). Shear deformation resulting from the large-scale (diameter of <100 km) Rheasilvia impact is proposed to form minor ridges (∼2 km to ∼25 km in length), which are interpreted as the surface expression of thrust faults, as well as grooves (∼3 km to ∼25 km in length) and pit crater chains (∼1 km to ∼25 km in length), which are interpreted as the surface expression of extension fractures and/or dilational normal faults. Secondary crater material, ejected from small-scale and medium-scale impacts (diameters of <100 km), are interpreted to form ejecta ray systems of grooves and crater chains by bouncing and scouring across the surface. Furthermore, seismic shaking, also resulting from small-scale and medium-scale impacts, is interpreted to form minor ridges because seismic shaking induces flow of regolith, which subsequently accumulates as minor ridges that are roughly parallel to the regional slope. In this work we expand upon the link between impact processes and structural features on Vesta by presenting findings of a photogeologic, structural mapping study which highlights how impact cratering and impact-related processes are expressed on this unique, intermediate Solar System body.

ContributorsScully, Jennifer E. C. (Author) / Yin, A. (Author) / Russell, C. T. (Author) / Buczkowski, D. L. (Author) / Williams, David (Author) / Blewett, D. T. (Author) / Ruesch, O. (Author) / Hiesinger, H. (Author) / Le Corre, L. (Author) / Mercer, Cameron (Author) / Yingst, R. A. (Author) / Garry, W. B. (Author) / Jaumann, R. (Author) / Roatsch, T. (Author) / Preusker, F. (Author) / Gaskell, R.W. (Author) / Schroder, S.E. (Author) / Ammannito, E. (Author) / Pieters, C. M. (Author) / Raymond, C. A. (Author) / DREAM 9 AML-OPC Consortium (Contributor)
Created2014-01-29