Matching Items (66)
Description
This dissertation investigates the condition of skeletal muscle insulin resistance using bioinformatics and computational biology approaches. Drawing from several studies and numerous data sources, I have attempted to uncover molecular mechanisms at multiple levels. From the detailed atomistic simulations of a single protein, to datamining approaches applied at the systems biology level, I provide new targets to explore for the research community. Furthermore I present a new online web resource that unifies various bioinformatics databases to enable discovery of relevant features in 3D protein structures.
ContributorsMielke, Clinton (Author) / Mandarino, Lawrence (Committee member) / LaBaer, Joshua (Committee member) / Magee, D. Mitchell (Committee member) / Dinu, Valentin (Committee member) / Willis, Wayne (Committee member) / Arizona State University (Publisher)
Created2013
Description
While exercising mammalian muscle increasingly relies on carbohydrates for fuel as aerobic exercise intensity rises above the moderate range, flying birds are extraordinary endurance athletes and fuel flight, a moderate-high intensity exercise, almost exclusively with lipid. In addition, Aves have long lifespans compared to weight-matched mammals. As skeletal muscle mitochondria account for the majority of oxygen consumption during aerobic exercise, the primary goal was to investigate differences in isolated muscle mitochondria between these species and to examine to what extent factors intrinsic to mitochondria may account for the behavior observed in the intact tissue and whole organism. First, maximal enzyme activities were assessed in sparrow and rat mitochondria. Citrate synthase and aspartate aminotransferase activity were higher in sparrow compared to rat mitochondria, while glutamate dehydrogenase activity was lower. Sparrow mitochondrial NAD-linked isocitrate dehydrogenase activity was dependent on phosphate, unlike the mammalian enzyme. Next, the rate of oxygen consumption (JO), electron transport chain (ETC) activity, and reactive oxygen species (ROS) production were assessed in intact mitochondria. Maximal rates of fat oxidation were lower than for carbohydrate in rat but not sparrow mitochondria. ETC activity was higher in sparrows, but no differences were found in ROS production between species. Finally, fuel selection and control of respiration at three rates between rest and maximum were assessed. Mitochondrial fuel oxidation and selection mirrored that of the whole body; in rat mitochondria the reliance on carbohydrate increased as the rate of oxygen consumption increased, whereas fat dominated under all conditions in the sparrow. These data indicate fuel selection, at least in part, can be modulated at the level of the mitochondrial matrix when multiple substrates are present at saturating levels. As an increase in matrix oxidation-reduction potential has been linked to a suppression of fat oxidation and high ROS production, the high ETC activity relative to dehydrogenase activity in avian compared to mammalian mitochondria may result in lower matrix oxidation-reduction potential, allowing fatty acid oxidation to proceed while also resulting in low ROS production in vivo.
ContributorsKuzmiak, Sarah (Author) / Willis, Wayne T (Thesis advisor) / Mandarino, Lawrence (Committee member) / Sweazea, Karen (Committee member) / Harrison, Jon (Committee member) / Gadau, Juergen (Committee member) / Arizona State University (Publisher)
Created2012
Description
Clean water for drinking, food preparation, and bathing is essential for astronaut health and safety during long duration habitation of the International Space Station (ISS), including future missions to Mars. Despite stringent water treatment and recycling efforts on the ISS, it is impossible to completely prevent microbial contamination of onboard water supplies. In this work, we used a spaceflight analogue culture system to better understand how the microgravity environment can influence the pathogenesis-related characteristics of Burkholderia cepacia complex (Bcc), an opportunistic pathogen previously recovered from the ISS water system. The results of the present study suggest that there may be important differences in how this pathogen can respond and adapt to spaceflight and other low fluid shear environments encountered during their natural life cycles. Future studies are aimed at understanding the underlying mechanisms responsible for these phenotypes.
ContributorsKang, Bianca Younseon (Author) / Nickerson, Cheryl (Thesis director) / Barrila, Jennifer (Committee member) / Ott, Mark (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
In the digital humanities, there is a constant need to turn images and PDF files into plain text to apply analyses such as topic modelling, named entity recognition, and other techniques. However, although there exist different solutions to extract text embedded in PDF files or run OCR on images, they typically require additional training (for example, scholars have to learn how to use the command line) or are difficult to automate without programming skills. The Giles Ecosystem is a distributed system based on Apache Kafka that allows users to upload documents for text and image extraction. The system components are implemented using Java and the Spring Framework and are available under an Open Source license on GitHub (https://github.com/diging/).
ContributorsLessios-Damerow, Julia (Contributor) / Peirson, Erick (Contributor) / Laubichler, Manfred (Contributor) / ASU-SFI Center for Biosocial Complex Systems (Contributor)
Created2017-09-28
Description
Because collective cognition emerges from local signaling among group members, deciphering communication systems is crucial to understanding the underlying mechanisms. Alarm signals are widespread in the social insects and can elicit a variety of behavioral responses to danger, but the functional plasticity of these signals has not been well studied. Here we report an alarm pheromone in the ant Temnothorax rugatulus that elicits two different behaviors depending on context. When an ant was tethered inside an unfamiliar nest site and unable to move freely, she released a pheromone from her mandibular gland that signaled other ants to reject this nest as a potential new home, presumably to avoid potential danger. When the same pheromone was presented near the ants' home nest, they were instead attracted to it, presumably to respond to a threat to the colony. We used coupled gas chromatography/mass spectrometry to identify candidate compounds from the mandibular gland and tested each one in a nest choice bioassay. We found that 2,5-dimethylpyrazine was sufficient to induce rejection of a marked new nest and also to attract ants when released at the home nest. This is the first detailed investigation of chemical communication in the leptothoracine ants. We discuss the possibility that this pheromone's deterrent function can improve an emigrating colony's nest site selection performance.
ContributorsSasaki, Takao (Author) / Hoelldobler, Bert (Author) / Millar, Jocelyn G. (Author) / Pratt, Stephen (Author) / College of Liberal Arts and Sciences (Contributor) / School of Life Sciences (Contributor) / ASU-SFI Center for Biosocial Complex Systems (Contributor) / Center for Social Dynamics and Complexity (Contributor)
Created2014-09-01
Description
This research project investigated known and novel differential genetic variants and their associated molecular pathways involved in Type II diabetes mellitus for the purpose of improving diagnosis and treatment methods. The goal of this investigation was to 1) identify the genetic variants and SNPs in Type II diabetes to develop a gene regulatory pathway, and 2) utilize this pathway to determine suitable drug therapeutics for prevention and treatment. Using a Gene Set Enrichment Analysis (GSEA), a set of 1000 gene identifiers from a Mayo Clinic database was analyzed to determine the most significant genetic variants related to insulin signaling pathways involved in Type II Diabetes. The following genes were identified: NRAS, KRAS, PIK3CA, PDE3B, TSC1, AKT3, SOS1, NEU1, PRKAA2, AMPK, and ACC. In an extensive literature review and cross-analysis with Kegg and Reactome pathway databases, novel SNPs located on these gene variants were identified and used to determine suitable drug therapeutics for treatment. Overall, understanding how genetic mutations affect target gene function related to Type II Diabetes disease pathology is crucial to the development of effective diagnosis and treatment. This project provides new insight into the molecular basis of the Type II Diabetes, serving to help untangle the regulatory complexity of the disease and aid in the advancement of diagnosis and treatment. Keywords: Type II Diabetes mellitus, Gene Set Enrichment Analysis, genetic variants, KEGG Insulin Pathway, gene-regulatory pathway
ContributorsBucklin, Lindsay (Co-author) / Davis, Vanessa (Co-author) / Holechek, Susan (Thesis director) / Wang, Junwen (Committee member) / Nyarige, Verah (Committee member) / School of Human Evolution & Social Change (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Spaceflight and spaceflight analogue culture enhance the virulence and pathogenesis-related stress resistance of the foodborne pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium). This is an alarming finding as it suggests that astronauts may have an increased risk of infection during spaceflight. This risk is further exacerbated as multiple studies indicate that spaceflight negatively impacts aspects of the immune system. In order to ensure astronaut safety during long term missions, it is important to study the phenotypic effects of the microgravity environment on a range of medically important microbial pathogens that might be encountered by the crew. This ground-based study uses the NASA-engineered Rotating Wall Vessel (RWV) bioreactor as a spaceflight analogue culture system to grow bacteria under low fluid shear forces relative to those encountered in microgravity, and interestingly, in the intestinal tract during infection. The culture environment in the RWV is commonly referred to as low shear modeled microgravity (LSMMG). In this study, we characterized the stationary phase stress response of the enteric pathogen, Salmonella enterica serovar Enteritidis (S. Enteritidis), to LSMMG culture. We showed that LSMMG enhanced the resistance of stationary phase cultures of S. Enteritidis to acid and thermal stressors, which differed from the LSSMG stationary phase response of the closely related pathovar, S. Typhimurium. Interestingly, LSMMG increased the ability of both S. Enteritidis and S. Typhimurium to adhere to, invade into, and survive within an in vitro 3-D intestinal co-culture model containing immune cells. Our results indicate that LSMMG regulates pathogenesis-related characteristics of S. Enteritidis in ways that may present an increased health risk to astronauts during spaceflight missions.
ContributorsKoroli, Sara (Author) / Nickerson, Cheryl (Thesis director) / Barrila, Jennifer (Committee member) / Ott, C. Mark (Committee member) / School of Life Sciences (Contributor) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
The International Space Station (ISS) utilizes recycled water for consumption, cleaning and air humidity control. The Environmental Control and Life Support Systems (ECLSS) have been rigorously tested at the NASA Johnson Space Center. Despite the advanced engineering of the water recovery system, bacterial biofilms have been recovered from this potable water source. Microbial contamination of potable water poses a potential threat to crew members onboard the ISS. Because astronauts have been found to have compromised immune systems, bacterial strains that would not typically be considered a danger must be carefully studied to better understand the mechanisms enabling their survival, including polymicrobial interactions. The need for a more thorough understanding of the effect of spaceflight environment on polymicrobial interactions and potential impact on crew health and vehicle integrity is heightened since 1) several potential pathogens have been isolated from the ISS potable water system, 2) spaceflight has been shown to induce unexpected alterations in microbial responses, and 3) emergent phenotypes are often observed when multiple bacterial species are co- cultured together, as compared to pure cultures of single species. In order to address these concerns, suitable growth media are required that will not only support the isolation of these microbes but also the ability to distinguish between them when grown as mixed cultures. In this study, selective and/or differential media were developed for bacterial isolates collected from the ISS potable water supply. In addition to facilitating discrimination between bacteria, the ideal media for each strain was intended to have a 100% recovery rate compared to traditional R2A media. Antibiotic and reagent susceptibility and resistance tests were conducted for the purpose of developing each individual medium. To study a wide range of targets, 12 antibiotics were selected from seven major classes, including penicillin, cephalosporins, fluoroquinolones, aminoglycosides, glycopeptides/lipoglycopeptides, macrolides/lincosamides/streptogramins, tetracyclines, in addition to seven unclassified antibiotics and three reagents. Once developed, medium efficacy was determined by means of growth curve experiments. The development of these media is a critical step for further research into the mechanisms utilized by these strains to survive the harsh conditions of the ISS water system. Furthermore, with an understanding of the complex nature of these polymicrobial communities, specific contamination targeting and control can be conducted to reduce the risk to crew members. Understanding these microbial species and their susceptibilities has potential application for future NASA human explorations, including those to Mars.
ContributorsKing, Olivia Grace (Author) / Nickerson, Cheryl (Thesis director) / Barrila, Jennifer (Committee member) / Ott, Mark (Committee member) / School of Sustainability (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-12
Description
This research project investigated known and novel differential genetic variants and their associated molecular pathways involved in Type II diabetes mellitus for the purpose of improving diagnosis and treatment methods. The goal of this investigation was to 1) identify the genetic variants and SNPs in Type II diabetes to develop a gene regulatory pathway, and 2) utilize this pathway to determine suitable drug therapeutics for prevention and treatment. Using a Gene Set Enrichment Analysis (GSEA), a set of 1000 gene identifiers from a Mayo Clinic database was analyzed to determine the most significant genetic variants related to insulin signaling pathways involved in Type II Diabetes. The following genes were identified: NRAS, KRAS, PIK3CA, PDE3B, TSC1, AKT3, SOS1, NEU1, PRKAA2, AMPK, and ACC. In an extensive literature review and cross-analysis with Kegg and Reactome pathway databases, novel SNPs located on these gene variants were identified and used to determine suitable drug therapeutics for treatment. Overall, understanding how genetic mutations affect target gene function related to Type II Diabetes disease pathology is crucial to the development of effective diagnosis and treatment. This project provides new insight into the molecular basis of the Type II Diabetes, serving to help untangle the regulatory complexity of the disease and aid in the advancement of diagnosis and treatment.
ContributorsDavis, Vanessa Brooke (Co-author) / Bucklin, Lindsay (Co-author) / Holechek, Susan (Thesis director) / Wang, Junwen (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
High throughput transcriptome data analysis like Single-cell Ribonucleic Acid sequencing (scRNA-seq) and Circular Ribonucleic Acid (circRNA) data have made significant breakthroughs, especially in cancer genomics. Analysis of transcriptome time series data is core in identifying time point(s) where drastic changes in gene transcription are associated with homeostatic to non-homeostatic cellular transition (tipping points). In Chapter 2 of this dissertation, I present a novel cell-type specific and co-expression-based tipping point detection method to identify target gene (TG) versus transcription factor (TF) pairs whose differential co-expression across time points drive biological changes in different cell types and the time point when these changes are observed. This method was applied to scRNA-seq data sets from a SARS-CoV-2 study (18 time points), a human cerebellum development study (9 time points), and a lung injury study (18 time points). Similarly, leveraging transcriptome data across treatment time points, I developed methodologies to identify treatment-induced and cell-type specific differentially co-expressed pairs (DCEPs). In part one of Chapter 3, I presented a pipeline that used a series of statistical tests to detect DCEPs. This method was applied to scRNA-seq data of patients with non-small cell lung cancer (NSCLC) sequenced across cancer treatment times. However, this pipeline does not account for correlations among multiple single cells from the same sample and correlations among multiple samples from the same patient. In Part 2 of Chapter 3, I presented a solution to this problem using a mixed-effect model. In Chapter 4, I present a summary of my work that focused on the cross-species analysis of circRNA transcriptome time series data. I compared circRNA profiles in neonatal pig and mouse hearts, identified orthologous circRNAs, and discussed regulation mechanisms of cardiomyocyte proliferation and myocardial regeneration conserved between mouse and pig at different time points.
ContributorsNyarige, Verah Mocheche (Author) / Liu, Li (Thesis advisor) / Wang, Junwen (Thesis advisor) / Dinu, Valentin (Committee member) / Arizona State University (Publisher)
Created2022