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Phenotypic and transcriptomic consequences of ribosomal DNA copy number variation in Caenorhabditis elegans and Saccharomyces cerevisiae
Ribosomal DNA (rDNA) forms the template for mature ribosomal RNA (rRNA) and shows considerable sequence conservation through evolution. In eukaryotic genomes rDNA is present in one or more tandem repeat arrays, with copy number variation (CNV) commonly observed in inter- and intra-species comparisons. rDNA CNV has been primarily studied in the budding yeast Saccharomyces cerevisiae, where an environmentally sensitive copy number amplification mechanism corrects for repeat loss from this inherently unstable locus. Furthermore, there is much evidence implicating rDNA instability and production of extrachromosomal rDNA circles (ERCs) as causative processes in yeast replicative ageing. By contrast, the functional consequences of rDNA CNV have been largely understudied in metazoans and as such rDNA CNV represents a source of poorly understood genomic variation. I undertook this project to investigate possible functional and transcriptomic consequences of rDNA CNV in an animal model, the nematode Caenorhabditis elegans. Additionally, I produced and analysed RNA-seq datasets studying the transcriptomic effects of rDNA CNV, either due to genomic CNV or ERC accumulation, in S. cerevisiae.
After developing methods for assaying rDNA copy number in C. elegans by pulsed field gel electrophoresis (PFGE) and quantitative PCR, I determined that there was notable variation between and within laboratory strains. Using a genetic crossing strategy, I derived strains believed to be essentially isogenic with either wild type (WT) or approximately 2.5-fold amplified rDNA. A variety of phenotypic assays found generally small effect sizes for differences unambiguously attributed to rDNA CNV. Some experiments were, however, confounded by unexpected developmental differences and strain pathology, likely the consequence of unidentified background genetic variation. Transcriptomic analyses were consistent with these observations and revealed some genes differentially expressed between samples with different rDNA CN at either young or aged timepoints.
Comparison of log-phase yeast samples with divergent rDNA CN similarly revealed few differentially expressed genes, although gene ontology enrichment analysis suggested effects on specific processes such as ribosome biogenesis. I also generated and analysed an ageing RNA-seq dataset which demonstrated that rDNA CNV in the form of ERC accumulation has significant effects on the ageing transcriptome. ERC accumulation influences the expression of hundreds of genes with strong enrichment for several previously identified age-related processes. Finally, using Northern blotting, I identified a common set of changes in rRNA processing intermediates, reminiscent of stress-related effects, which occur with ageing in variety of genetic backgrounds
Dependence and Fundamentality
I argue that dependence is neither necessary nor sufficient for relative fundamentality. I then introduce the notion of 'likeness in nature' and provide an account of relative fundamentality in terms of it and the notion of dependence. Finally, I discuss some puzzles that arise in Aristotle's Categories, to which the theory developed is applied
(Re)Locating South Asian Womeni n Apna Ghar: Evolving Cultural Narratives within Domestic Violence Intervention
From the Washington University Senior Honors Thesis Abstracts (WUSHTA), Spring 2018. Published by the Office of Undergraduate Research. Joy Zalis Kiefer, Director of Undergraduate Research and Associate Dean in the College of Arts & Sciences; Lindsey Paunovich, Editor; Helen Human, Programs Manager and Assistant Dean in the College of Arts and Sciences Mentor: Jami Ak
Serious Education for Serious Christians
This paper is based on the Convocation Address given by Dr. Carl Zylstra at Dordt College on August 27, 2010
A Call to Action: A Client-Centered Evaluation of Collaborative Law
This paper will first examine the process of collaborative law, from deciding to hire a collaborative lawyer to the disqualification agreement, as well as identifying potential dangers for the client, including an analysis of collaborative law utilizing the negotiation theory of Roger Fisher and William Ury\u27s book Getting to Yes. The second part of the paper will examine how collaborative law literature evaluates and critiques the costs and benefits of collaborative law. This paper ultimately finds that the cost-benefit analysis either stems from small, non-controlled studies or personal anecdotes, or discussions of whether collaborative law complies with ethics rules, both of which are practitioner-centered
HEDGING CLASS I MILK: THE "ACCELERATION" AND "MOVER" EFFECT
A volatile closing basis prevents class I hedgers from locking in a minimum price. The closing basis is composed of an "acceleration" and "mover" effect. The mover effect always works to the producer's advantage unlike the acceleration effect. This research discusses hedging strategies to minimize the acceleration effect.Marketing,
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