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Finding life beyond Earth could change our understanding of life and habitability. The best place to look for life beyond Earth is Jupiter's moon, Europa. It has been estimated Europa may have a liquid, salt-water subsurface with 2 to 3 times the volume of all Earth's oceans. Knowing that all life requires water, it is in our best interest to explore Europa. This thesis explored the plausibility of life on Europa in four of its environments: on the surface, under the ice shell, in the liquid subsurface, and at the bottom of the liquid subsurface. Each of these environments were defined from science literature and compared to known Earth analogs. Europa's surface is not likely to support life, as there is not liquid water present. There is also extremely high radiation bombardment and extremely low surface temperatures that are estimated to be well out of the range for supporting life. It is more plausible that life could be under Europa's ice shell than on the surface. Under the surface, radiation exposure dramatically reduces. Researchers have found organisms on Earth that can live in similar environments as Europa's ice as well. These organisms require some interaction with liquid water though. Uncertainties about Europa's ice shell thickness and radiation load per depth it experiences, as well as there being limited research on organisms in ice environments, hinder us from definitively assessing the plausibility of life under the surface. The best environment on Europa to look for life on Europa is the subsurface. There remain a lot of uncertainties about the subsurface, however, that make it difficult to assess the plausibility of finding life. These uncertainties include its depth, water activity, salinity, temperature, pressure, and structure. This subsurface may be suitable for life, but until we can further understand the environment of the subsurface, we cannot make definite conclusions. As for assessing the plausibility of life at the bottom of Europa's subsurface, there is not much we know about this environment either. It has been suggested there may be hydrothermal vents, but no evidence has either supported or rejected this idea. Without a clear understanding of the environment at the bottom of the subsurface, the plausibility of life here cannot be definitively answered. It is apparent we need to further study Europa. In particular, we need to focus on understanding the subsurface. When the subsurface is better defined, we can better assess the plausibility of life being present. Fortunately, both NASA and the ESA are currently planning missions to Europa that are scheduled to launch in the 2020s.
ContributorsHoward, Cheyenne Whiffen (Author) / Farmer, Jack (Thesis director) / Shock, Everett (Committee member) / School of Earth and Space Exploration (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
the project led by Professor Emma Frow, researching of stem cell clinics focused on stem cell applications, adherence to FDA guidelines, and characterization of information available and physician credentials. Regenerative medicine clinics commonly offered stem cell therapy, but introduced platelet rich plasma (PRP) and prolotherapy as regenerative therapies.
PRP and Prolotherapy are individual treatments that were even suggested and used in combination with stem cell therapies. Prolotherapy predates PRP as a chemical irritant therapy originally used to sclerose tissues. Prolotherapy is meant to stimulate platelet derived growth factors release to improve tissue healing response. Prolotherapy shows negligible efficacy improvements over corticosteroids, but may have underlying side effects from being an irritant. PRP is a more modern therapy for improved healing. Speculations state initial use was in an open heart surgery to improve healing post-surgery. PRP is created via centrifugation of patient blood to isolate growth factors by removing serum and other biological components to increase platelet concentration. PRP is comparable to corticosteroid injections in efficacy, but as an autologous application, there are no side effects making it more advantageous. Growth factors induce healing response and reduce inflammation. Growth factors stimulate cell growth, proliferation, differentiation, and stimulate cellular response mechanism such as angiogenesis and mitogenesis. The growth factor stimulation of PRP and prolotherapy both assist stem cell proliferation. Additional research is needed to determine differential capacity to ensure multipotent stem cells regenerate the correct cell type from the increased differential capacity offered by growth factor recruitment. The application of combination therapy for stem cells is unsubstantiated and applications violate FDA ‘minimal manipulation’ guidelines.
PRP and Prolotherapy are individual treatments that were even suggested and used in combination with stem cell therapies. Prolotherapy predates PRP as a chemical irritant therapy originally used to sclerose tissues. Prolotherapy is meant to stimulate platelet derived growth factors release to improve tissue healing response. Prolotherapy shows negligible efficacy improvements over corticosteroids, but may have underlying side effects from being an irritant. PRP is a more modern therapy for improved healing. Speculations state initial use was in an open heart surgery to improve healing post-surgery. PRP is created via centrifugation of patient blood to isolate growth factors by removing serum and other biological components to increase platelet concentration. PRP is comparable to corticosteroid injections in efficacy, but as an autologous application, there are no side effects making it more advantageous. Growth factors induce healing response and reduce inflammation. Growth factors stimulate cell growth, proliferation, differentiation, and stimulate cellular response mechanism such as angiogenesis and mitogenesis. The growth factor stimulation of PRP and prolotherapy both assist stem cell proliferation. Additional research is needed to determine differential capacity to ensure multipotent stem cells regenerate the correct cell type from the increased differential capacity offered by growth factor recruitment. The application of combination therapy for stem cells is unsubstantiated and applications violate FDA ‘minimal manipulation’ guidelines.
ContributorsKrum, Logan (Author) / Frow, Emma (Thesis director) / Brafman, David (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
With the rising data output and falling costs of Next Generation Sequencing technologies, research into data compression is crucial to maintaining storage efficiency and costs. High throughput sequencers such as the HiSeqX Ten can produce up to 1.8 terabases of data per run, and such large storage demands are even more important to consider for institutions that rely on their own servers rather than large data centers (cloud storage)1. Compression algorithms aim to reduce the amount of space taken up by large genomic datasets by encoding the most frequently occurring symbols with the shortest bit codewords and by changing the order of the data to make it easier to encode. Depending on the probability distribution of the symbols in the dataset or the structure of the data, choosing the wrong algorithm could result in a compressed file larger than the original or a poorly compressed file that results in a waste of time and space2. To test efficiency among compression algorithms for each file type, 37 open-source compression algorithms were used to compress six types of genomic datasets (FASTA, VCF, BCF, GFF, GTF, and SAM) and evaluated on compression speed, decompression speed, compression ratio, and file size using the benchmark test lzbench. Compressors that outpreformed the popular bioinformatics compressor Gzip (zlib -6) were evaluated against one another by ratio and speed for each file type and across the geometric means of all file types. Compressors that exhibited fast compression and decompression speeds were also evaluated by transmission time through variable speed internet pipes in scenarios where the file was compressed only once or compressed multiple times.
ContributorsHowell, Abigail (Author) / Cartwright, Reed (Thesis director) / Wilson Sayres, Melissa (Committee member) / Taylor, Jay (Committee member) / Barrett, The Honors College (Contributor)
Created2017-05
Description
Many bacteria actively import environmental DNA and incorporate it into their genomes. This behavior, referred to as transformation, has been described in many species from diverse taxonomic backgrounds. Transformation is expected to carry some selective advantages similar to those postulated for meiotic sex in eukaryotes. However, the accumulation of loss-of-function alleles at transformation loci and an increased mutational load from recombining with DNA from dead cells create additional costs to transformation. These costs have been shown to outweigh many of the benefits of recombination under a variety of likely parameters. We investigate an additional proposed benefit of sexual recombination, the Red Queen hypothesis, as it relates to bacterial transformation. Here we describe a computational model showing that host-pathogen coevolution may provide a large selective benefit to transformation and allow transforming cells to invade an environment dominated by otherwise equal non-transformers. Furthermore, we observe that host-pathogen dynamics cause the selection pressure on transformation to vary extensively in time, explaining the tight regulation and wide variety of rates observed in naturally competent bacteria. Host-pathogen dynamics may explain the evolution and maintenance of natural competence despite its associated costs.
ContributorsPalmer, Nathan David (Author) / Cartwright, Reed (Thesis director) / Wang, Xuan (Committee member) / Sievert, Chris (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Current research into live-cell dynamics, particularly those relating to chromatin structure and remodeling, are limited. The tools that are used to detect state changes in chromatin, such as Chromatin Immunoprecipitation and qPCR, require that the cell be killed off. This limits the ability of researchers to pinpoint changes in live cells over a longer period of time. As such, there is a need for a live-cell sensor that can detect chromatin state changes. The Chromometer is a transgenic chromatin state sensor designed to better understand human cell fate and the chromatin changes that occur. HOXD11.12, a DNA sequence that attracts repressive Polycomb group (PCG) proteins, was placed upstream of a core promoter-driven fluorescent reporter (AmCyan fluorescent protein, CFP) to link chromatin repression to a CFP signal. The transgene was stably inserted at an ectopic site in U2-OS (osteosarcoma) cells. Expression of CFP should reflect the epigenetic state at the HOXD locus, where several genes are regulated by Polycomb to control cell differentiation. U2-OS cells were transfected with the transgene and grown under selective pressure. Twelve colonies were identified as having integrated parts from the transgene into their genomes. PCR testing verified 2 cell lines that contain the complete transgene. Flow cytometry indicated mono-modal and bimodal populations in all transgenic cell colonies. Further research must be done to determine the effectiveness of this device as a sensor for live cell state change detection.
ContributorsBarclay, David (Co-author) / Simper, Jan (Co-author) / Haynes, Karmella (Thesis director) / Brafman, David (Committee member) / School of Life Sciences (Contributor) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Mammary gland development in humans during puberty involves the enlargement of breast tissue, but this is not true in non-human primates. To identify potential causes of this difference, I examined variation in substitution rates across genes related to mammary development. Genes undergoing purifying selection show slower-than-average substitution rates, while genes undergoing positive selection show faster rates. These may be related to the difference between humans and other primates. Three genes were found to be accelerated were FOXF1, IGFBP5, and ATP2B2, but only the latter one was found in humans and it seems unlikely that it would be related to the differences between mammary gland development at puberty between humans and non-human primates.
ContributorsArroyo, Diana (Author) / Cartwright, Reed (Thesis director) / Wilson Sayres, Melissa (Committee member) / Schwartz, Rachel (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Yellowstone National Park has a vibrant variety of flora, fauna, and hydrothermal systems all collected together in one large and complex system. Studies have been conducted for at least several decades in order to make sense of this system in ways that may be relevant to other similar geologies around the world. The latest update in this ever-ongoing study involves the collection and analysis of water samples from 2016. These samples have been analyzed for conductivity, pH, temperature, dissolved organic carbon, dissolved inorganic carbon, carbon isotopes, dissolved oxygen, ferrous iron, sulfide, silica, and more. While not many trends were found in this data in regards to dissolved organic carbon values, this is a substantial addition to a growing body of information that could yield more impressive information in times to come. In addition, factors that have yet to analyzed for this 2016 data, such as concentrations of metals and metalloids, may provide some insights when put through a chloride vs sulfate framework to separate out different reaction regions.
ContributorsDoan, Cuong Le (Author) / Shock, Everett (Thesis director) / Gould, Ian (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
The ability to find evidence of life on early Earth and other planets is constrained by the current understanding of biosignatures and our ability to differentiate fossils from abiotic mimics. When organisms transition from the living realm to the fossil record, their morphological and chemical characteristics are modified, usually resulting in the loss of information. These modifications can happen during early and late diagenesis and differ depending on local geochemical properties. These post-depositional modifications need to be understood to better interpret the fossil record. Siliceous hot spring deposits (sinters) are of particular interest for biosignature research as they are early Earth analog environments and targets for investigating the presence of fossil life on Mars. As silica-supersaturated fluids flow from the vent to the distal apron, they precipitate non-crystalline opal-A that fossilizes microbial communities at a range in scales (μm-cm). Therefore, many studies have documented the ties between the active microbial communities and the morphological and chemical biosignatures in hot springs. However, far less attention has been placed on understanding preservation in systems with complex mineralogy or how post-depositional alteration affects the retention of biosignatures. Without this context, it can be challenging to recognize biosignatures in ancient rocks. This dissertation research aims to refine our current understanding of biosignature preservation and retention in sinters. Biosignatures of interest include organic matter, microfossils, and biofabrics. The complex nature of hot springs requires a comprehensive understanding of biosignature preservation that is representative of variable chemistries and post-depositional alterations. For this reason, this dissertation research chapters are field site-based. Chapter 2 investigates biosignature preservation in an unusual spring with mixed opal-A-calcite mineralogy at Lýsuhóll, Iceland. Chapter 3 tracks how silica diagenesis modifies microfossil morphology and associated organic matter at Puchuldiza, Chile. Chapter 4 studies the effects of acid fumarolic overprinting on biosignatures in Gunnuhver, Iceland. To accomplish this, traditional geologic methods (mapping, petrography, X-ray diffraction, bulk elemental analyses) were combined with high-spatial-resolution elemental mapping to better understand diagenetic effects in these systems. Preservation models were developed to predict the types and styles of biosignatures that can be present depending on the depositional and geochemical context. Recommendations are also made for the types of deposits that are most likely to preserve biosignatures.
ContributorsJuarez Rivera, Marisol (Author) / Farmer, Jack D (Thesis advisor) / Hartnett, Hilairy E (Committee member) / Shock, Everett (Committee member) / Garcia-Pichel, Ferran (Committee member) / Trembath-Reichert, Elizabeth (Committee member) / Arizona State University (Publisher)
Created2021
Description
Cardiovascular disease (CVD) remains the leading cause of mortality, resulting in 1 out of 4 deaths in the United States at the alarming rate of 1 death every 36 seconds, despite great efforts in ongoing research. In vitro research to study CVDs has had limited success, due to lack of biomimicry and structural complexity of 2D models. As such, there is a critical need to develop a 3D, biomimetic human cardiac tissue within precisely engineered in vitro platforms. This PhD dissertation involved development of an innovative anisotropic 3D human stem cell-derived cardiac tissue on-a-chip model (i.e., heart on-a-chip), with an enhanced maturation tissue state, as demonstrated through extensive biological assessments. To demonstrate the potential of the platform to study cardiac-specific diseases, the developed heart on-a-chip was used to model myocardial infarction (MI) due to exposure to hypoxia. The successful induction of MI on-a-chip (heart attack-on-a-chip) was evidenced through fibrotic tissue response, contractile dysregulation, and transcriptomic regulation of key pathways.This dissertation also described incorporation of CRISPR/Cas9 gene-editing to create a human induced pluripotent stem cell line (hiPSC) with a mutation in KCNH2, the gene implicated in Long QT Syndrome Type 2 (LQTS2). This novel stem cell line, combined with the developed heart on-a-chip technology, led to creation of a 3D human cardiac on-chip tissue model of LQTS2 disease.. Extensive mechanistic biological and electrophysiological characterizations were performed to elucidate the mechanism of R531W mutation in KCNH2, significantly adding to existing knowledge about LQTS2. In summary, this thesis described creation of a LQTS2 cardiac on-a-chip model, incorporated with gene-edited hiPSC-cardiomyocytes and hiPSC-cardiac fibroblasts, to study mechanisms of LQTS2.
Overall, this dissertation provides broad impact for fundamental studies toward cardiac biological studies as well as drug screening applications. Specifically, the developed heart on-a-chip from this dissertation provides a unique alternative platform to animal testing and 2D studies that recapitulates the human myocardium, with capabilities to model critical CVDs to study disease mechanisms, and/or ultimately lead to development of future therapeutic strategies.
ContributorsVeldhuizen, Jaimeson (Author) / Nikkhah, Mehdi (Thesis advisor) / Brafman, David (Committee member) / Ebrahimkhani, Mo (Committee member) / Migrino, Raymond Q (Committee member) / Plaisier, Christopher (Committee member) / Arizona State University (Publisher)
Created2021
Description
Skin wounds can be caused by traumatic lacerations or incisions which disrupt the structural and functional integrity of the skin. Wound closure and primary intention treatment of the wound as soon as possible is crucial to avoid or minimize the risk of infection that can result in a compromised healing rate or advanced functional intricacy. The gold standard treatment for skin wound healing is suturing. Light-activated tissue sealing is an appealing alternative to sutures as it seals the wound edges minimizing the risk of infection and scarring, especially when utilized along with biodegradable polymeric biomaterials in the wound bed. Silk fibroins can be used as a biodegradable biomaterial that possesses properties supporting cell migration and proliferation in the tissue it interacts with. In addition, histamine treatment is shown to have extensive effects on cellular functions promoting wound healing. Here, the evaluation of Laser-activated Sealants (LASE) consisting of silk fibroin films induced with Indocyanine Green dye in a wound sealed with laser in the presence of Histamine receptor agonists H1R, H2R and H4R take place. The results were evaluated using Trans-epidermal Water Loss (TEWL), histological and analytical techniques where immune cell biomarkers Arginase-1, Ly6G, iNOS, Alpha-SMA, Proliferating Cell Nuclear Antigen (PCNA), and E-Cadherin were used to study the activity of specific cells such as macrophages, neutrophils, and myofibroblasts that aid in wound healing. PBS was used as a control for histamine receptor agonists. It was found that TEWL increased when treated with H1 receptor agonists while decreasing significantly in H2R and H4R-treated wounds. Arginase-1 activity improved, while it displayed an inverse relationship compared to iNOS. H4R agonist escalated Alpha-SMA cells, while others did not have any significant difference. Ly6G activity depleted in all histamine agonists significantly, while PCNA and E-Cadherin failed to show a positive or negative effect.
ContributorsPatel, Dirghau Manishbhai (Author) / Rege, Kaushal (Thesis advisor) / Massia, Stephen (Committee member) / Brafman, David (Committee member) / Arizona State University (Publisher)
Created2022