Matching Items (235)
Description
The field of biologic research is particularly concerned with understanding nature's complex dynamics. From deducing anatomical structures to studying behavioral patterns, evolutionary theory has developed greatly beyond the simple notions proposed by Charles Darwin. However, because it rarely considers the concept of complexity, modern evolutionary theory retains some descriptive weakness. This project represents an explorative approach for considering complexity and whether it plays an active role in the development of biotic systems. A novel theoretical framework, titled the Genesis Mechanism, was formulated reconsidering the major tenets of evolutionary theory to include complexity as a universal tendency. Within this framework, a phenomenon, referred to as "social transitioning," occurs between higher orders of complexity. Several potential properties of social transitions were proposed and analyzed in order to validate the theoretical concepts proposed within the Genesis Mechanism. The successful results obtained through this project's completion help demonstrate the scientific necessity for understanding complexity from a more fundamental, biologic standpoint.
ContributorsMcAuliffe, Jacob (Author) / Laubichler, Manfred (Thesis director) / Armendt, Brad (Committee member) / Barrett, The Honors College (Contributor)
Created2013-05
Description
Protein AMPylation is a recently discovered and relatively unstudied post-translational modification (PTM). AMPylation has previously been shown to play an important role in metabolic regulation and host pathogenesis in bacteria, but the recent identification of potential AMPylators across many species in every domain of life has supported the possibility that AMPylation could be a more fundamental and physiologically significant regulatory PTM. For the first time, we characterized the auto-AMPylation capability of the human protein SOS1 through in vitro AMPylation experiments using full-length protein and whole-domain truncation mutants. We found that SOS1 can become AMPylated at a tyrosine residue possibly within the Cdc25 domain of the protein, the Dbl homology domain is vital for efficient auto-AMPylation activity, and the C-terminal proline-rich domain exhibits a complex regulatory function. The proline-rich domain alone also appears to be capable of catalyzing a separate, unidentified covalent self-modification using a fluorescent ATP analogue. Finally, SOS1 was shown to be capable of catalyzing the AMPylation of two endogenous human protein substrates: a ubiquitous, unidentified protein of ~49kDa and another breast-cancer specific, unidentified protein of ~28kDa.
ContributorsOber-Reynolds, Benjamin John (Author) / LaBaer, Joshua (Thesis director) / Borges, Chad (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / School of Life Sciences (Contributor)
Created2014-05
Description
Analysis of 4 lesson plans for primary education in which 3D printers are used either to build components or are directly used by students. Provides critique on how proper investment and utilization of this new technology can enrich education and misuse can waste time, money, and even reduce the quality of education.
ContributorsPrzeslica, Michael Cody (Author) / Adams, James (Thesis director) / Krause, Stephen (Committee member) / Barrett, The Honors College (Contributor) / Materials Science and Engineering Program (Contributor)
Created2014-05
Description
AMPylation is a post-translation modification that has an important role in the survival of many bacterial pathogens by affecting the host cell's molecular signaling. In the course of studying this intercellular manipulation, there has only been modest progression in the identification of the enzymes with AMPylation capabilities (AMPylators) and their respective targets. The reason for these minimal developments is the inability to analyze a large subset of these proteins. Therefore, to increase the efficiency of the identification and characterization of the proteins, Yu et al developed a high-throughput non-radioactive discovery platform using Human Nucleic Acid Programmable Protein Arrays (NAPPA) and a validation platform using bead-based assays. The large-scale unbiased screening of potential substrates for two bacterial AMPylators containing Fic domain, VopS and IbpAFic2, had been performed and dozens of novel substrates were identified and confirmed. With the efficiency of this method, the platform was extended to the identification of novel substrates for a Legionella virulence factor, SidM, containing a different adenylyl transferase domain. The screening was performed using NAPPA arrays comprising of 10,000 human proteins, the active AMPylator SidM, and its inactive D110/112A mutant as a negative control. Many potential substrates of SidM were found, including Rab GTPases and non-GTPase proteins. Several of which have been confirmed with the bead-based AMPylation assays.
ContributorsGraves, Morgan C. (Author) / LaBaer, Joshua (Thesis director) / Qiu, Ji (Committee member) / Yu, Xiaobo (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2013-05
Description
In this thesis, glycan nodes, the basic subunits of complex biological sugars, were studied to determine the reproducibility of gas chromatography-mass spectrometry (GC/MS) based methylation analysis of whole blood plasma by normalization using an internal standard of heavy permethylated glycans. Glycans are complex biological sugars that have a variety of applications in the human body and will display aberrant compositions when produced by cancerous cells. Thus an assay to determine their composition can be used as a diagnostic tool. It was shown that the assay may have potential use, but needs further refinement to become an improvement over current methods by analyzing the results of ratio-determination and replicate experiments.
ContributorsMiyasaki, Tyler Takeo (Author) / Borges, Chad (Thesis director) / Van Horn, Wade (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / Chemical Engineering Program (Contributor)
Created2015-05
Description
Western diets, high in dietary fat and red meat, are associated with hyperglycemia and weight gain, symptoms that promote insulin resistance and diabetes. Previous studies have shown that elevated glucose promotes glycation of circulating proteins such as albumin, which is thought to lead to hyperglycemia complications. It was hypothesized that diets with no meat consumption (pesco-vegetarian and lacto-vegetarian) would reduce protein glycation, in comparison to a diet with meat. Forty six healthy adult omnivorous subjects were randomized into one of three groups and instructed to either consume red meat (i.e. meat) or poultry twice per day (control), eliminate meat and increase fish consumption (pesco-vegetarian), or adopt a vegetarian diet devoid of fish, meat or poultry (lacto-vegetarian) for four weeks. Fasting plasma samples were collected from participants at baseline and after 4 weeks of the dietary intervention. Plasma glucose concentrations were measured using a commercially available kit. Percent glycated albumin was measured on a separate aliquot of plasma by mass spectrometry. Plasma glucose concentrations were significantly increased following 4-weeks of pesco-vegetarian diet (P=0.002, paired t-test). Neither the lacto-vegetarian (P=0.898) or the control diet (P=0.233) affected plasma glucose concentrations. Despite the significant increase in plasma glucose following a pesco-vegetarian diet, no change in percent glycated albumin was observed (P>0.50, ANOVA). These findings may indicate a protective effect of the pesco-vegetarian diet on protein glycation in the presence of elevated plasma glucose and suggest the need for additional studies to examine the link between increased fish consumption and glucose regulation.
ContributorsRaad, Noor (Author) / Sweazea, Karen (Thesis director, Committee member) / Borges, Chad (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
Studies in neocortical neurogenesis have experienced an explosive growth since the early 2000s, measured by the increasing number of publications each year. I examine here the influence of Arnold Kriegstein in the field using Topic Modeling, a set of algorithms that can be applied to a collection of texts to elucidate the central themes of said collection. Using a Java-based software called MALLET, I obtained data for his corpus, and compared it to the texts of other researchers in the field. This latter collection, which I dub "General Corpus", was separated by year from 2000 to 2014. I found that Kriegstein's most frequently discussed topic concerned highly unique terms such as GABA, glutamate, and receptor, which did not appear in any of the primary topics of the General Corpus. This was in contrast to my initial hypothesis that Kriegstein's importance stemmed from his examination of different phenomena that constitute the broader aspect of neocortical neurogenesis. I predicted that the terms in Kriegstein's primary topic would appear many times throughout the topics of the General Corpus, but it was not so, aside from the common ones such as neurons, cortical, and development. Taken in tandem with NIH Reporter data, these results suggest that Kriegstein obtains a large amount of research funding because his studies concern unique topics when compared to others in the field. The implications of these findings are especially relevant in a world where funding is becoming increasingly difficult to come by.
ContributorsChhetri, Chandra Divyash (Author) / Laubichler, Manfred (Thesis director) / Maienschein, Jane (Committee member) / Aiello, Kenneth (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
The purpose of this project was to identify proteins associated with the migration and invasion of non-transformed MCF10A mammary epithelial cells with ectopically expressed missense mutations in p53. Because of the prevalence of TP53 missense mutations in basal-like and triple-negative breast cancer tumors, understanding the effect of TP53 mutations on the phenotypic expression of human mammary epithelial cells may offer new therapeutic targets for those currently lacking in treatment options. As such, MCF10A mammary epithelial cells ectopically overexpressing structural mutations (G245S, H179R, R175H, Y163C, Y220C, and Y234C) and DNA-binding mutations (R248Q, R248W, R273C, and R273H) in the DNA-binding domain were selected for use in this project. Overexpression of p53 in the mutant cell lines was confirmed by western blot and q-PCR analysis targeting the V5 epitope tag present in the pLenti4 vector used to transduce TP53 into the mutant cell lines. Characterization of the invasion and migration phenotypes resulting from the overexpression of p53 in the mutant cell lines was achieved using transwell invasion and migration assays with Boyden chambers. Statistical analysis showed that three cell lines—DNA-contact mutants R248W and R273C and structural mutant Y220C—were consistently more migratory and invasive and demonstrated a relationship between the migration and invasion properties of the mutant cell lines. Two families of proteins were then explored: those involved in the Epithelial-Mesenchymal Transition (EMT) and matrix metalloproteinases (MMPs). Results of q-PCR and immunofluorescence analysis of epithelial marker E-cadherin and mesenchymal proteins Slug and Vimentin did not show a clear relationship between mRNA and protein expression levels with the migration and invasiveness phenotypes observed in the transwell studies. Results of western blotting, q-PCR, and zymography of MMP-2 and MMP-9 also did not show any consistent results indicating a definite relationship between MMPs and the overall invasiveness of the cells. Finally, two drugs were tested as possible treatments inhibiting invasiveness: ebselen and SBI-183. These drugs were tested on only the most invasive of the MCF10A p53 mutant cell lines (R248W, R273C, and Y220C). Results of invasion assay following 30 μM treatment with ebselen and SBI-183 showed that ebselen does not inhibit invasiveness; SBI-183, however, did inhibit invasiveness in all three cell lines tested. As such, SBI-183 will be an important compound to study in the future as a treatment that could potentially serve to benefit triple-negative or basal-like breast cancer patients who currently lack therapeutic treatment options.
ContributorsZhang, Kathie Q (Author) / LaBaer, Joshua (Thesis director) / Anderson, Karen (Committee member) / Gonzalez, Laura (Committee member) / Barrett, The Honors College (Contributor) / School of International Letters and Cultures (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2015-05
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
Despite the fact that seizures are commonly associated with autism spectrum disorder (ASD), the effectiveness of treatments for seizures has not been well studied in individuals with ASD. This manuscript reviews both traditional and novel treatments for seizures associated with ASD. Studies were selected by systematically searching major electronic databases and by a panel of experts that treat ASD individuals. Only a few anti-epileptic drugs (AEDs) have undergone carefully controlled trials in ASD, but these trials examined outcomes other than seizures. Several lines of evidence point to valproate, lamotrigine, and levetiracetam as the most effective and tolerable AEDs for individuals with ASD. Limited evidence supports the use of traditional non-AED treatments, such as the ketogenic and modified Atkins diet, multiple subpial transections, immunomodulation, and neurofeedback treatments. Although specific treatments may be more appropriate for specific genetic and metabolic syndromes associated with ASD and seizures, there are few studies which have documented the effectiveness of treatments for seizures for specific syndromes. Limited evidence supports l-carnitine, multivitamins, and N-acetyl-l-cysteine in mitochondrial disease and dysfunction, folinic acid in cerebral folate abnormalities and early treatment with vigabatrin in tuberous sclerosis complex. Finally, there is limited evidence for a number of novel treatments, particularly magnesium with pyridoxine, omega-3 fatty acids, the gluten-free casein-free diet, and low-frequency repetitive transcranial magnetic simulation. Zinc and l-carnosine are potential novel treatments supported by basic research but not clinical studies. This review demonstrates the wide variety of treatments used to treat seizures in individuals with ASD as well as the striking lack of clinical trials performed to support the use of these treatments. Additional studies concerning these treatments for controlling seizures in individuals with ASD are warranted.
ContributorsFrye, Richard E. (Author) / Rossignol, Daniel (Author) / Casanova, Manuel F. (Author) / Brown, Gregory L. (Author) / Martin, Victoria (Author) / Edelson, Stephen (Author) / Coben, Robert (Author) / Lewine, Jeffrey (Author) / Slattery, John C. (Author) / Lau, Chrystal (Author) / Hardy, Paul (Author) / Fatemi, S. Hossein (Author) / Folsom, Timothy D. (Author) / MacFabe, Derrick (Author) / Adams, James (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2013-09-13