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The failure to balance protein synthesis, folding, and degradation in the endoplasmic reticulum (ER) leads to the accumulation of unfolded proteins, leading to ER stress. Cells respond to this stress by activating a response signaling pathway known as the Unfolded Protein Response (UPR). One of the branches of the UPR induces the phosphorylation of eIF2α (Eukaryotic Initiation Factor 2) to attenuate global protein synthesis, allowing for a chance to clear misfolded and unfolded proteins. This phosphorylation of eIF2α is opposed by a phosphatase, containing a catalytic subunit, Protein Phosphatase 1, and a scaffolding protein, either GADD34 or CReP. Inhibition of eIF2α phosphatases has shown to promote survival in cell types by prolonging the effects of the UPR. This research focuses on understanding the gene expression patterns and localization of UPR specific genes with the presence of constant ER stress. Zebrafish are an ideal model for this research because they are a good mimic of what happens in humans and provide the ability to study gene expression and localization patterns at different stages during ER stress and its recovery. The eIF2α phosphatases were shown to have a protective effect on apoptosis when overexpressed in acute ER stress but were shown to have a protective effect on apoptosis when knocked out in chronic ER stress. We sought to determine the flow of gene expression of these phosphatases as well as other UPR specific genes, such as BiP and CHOP, to determine the contradictory effects of acute versus chronic ER-stress induced apoptosis. We studied the changes in gene expression for these genes in zebrafish embryos by isolating RNA and performing RT-qPCR after the induction of ER stress with pharmacological drugs across multiple time points. There was increased gene upregulation and mRNA localization to the fin epidermis and eye of GADD34, CReP, and BiP in acute ER stress from 2 hours to 6 hours, and these genes steadily declined in chronic ER stress from 24 hours to 48 hours. CHOP is a late-phase pro-apoptotic protein whose gene expression was upregulated in chronic ER stress from 12 hours to 48 hours. This data was also supported by mRNA localization studies performed by conducting whole mount in-situ hybridization on zebrafish embryos treated with ER stress inducers for 4 hours and 24 hours. Our results indicate that all UPR genes examined are affected by ER stress and their expression patterns are dependent on the time length of ER stress induction, allowing us to get a more in-depth working model of this branch of the UPR signaling pathway in zebrafish.

This thesis explores a novel’s potential transformations when adapted into the easy-reader format. In early 2021, two distinct easy-reader adaptations of George Orwell’s 1984 were published, accompanied by a new translation of the original full-length version. This analysis primarily seeks to study whether the theme of surveillance undergoes alteration in the easy- reader adaptations, potentially becoming stricter or facilitating a more nuanced interpretation. A notable difference in length among the three versions was observed; when compared as audiobooks at a consistent speed (words per minute), their durations are as follows: the original text: 10 hours and 7 minutes, adapted text 1 by Book Publisher Hedvig: 2 hours and 9 minutes, and adapted text 2 by Vilja Publisher: 33 minutes. Employing comparative close reading and drawing on narratological theory, this study is inspired by the distinctions between round and flat characters, as discussed by E.M. Forster, Maria Nikolajeva, and Mieke Bal. Regarding the theme of surveillance, the thesis concludes that the adaptations do not exhibit as drastic changes as one might anticipate. Analysis of the characters’ transformations in response to surveillance reveals that their portrayal becomes harsher and more rugged in the easy-reader versions compared to the original text. Nevertheless, the shortest adapted text maintains the closest resemblance to the original.

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Fibroproliferative disorders are the leading cause of morbidity and mortality worldwide, with one specific group of fibroproliferative disorders being interstitial lung diseases (ILD). Idiopathic pulmonary fibrosis is the most common ILD; however its pathogenesis is not entirely understood. What is known is that there is repetitive cellular injury preceding the fibrotic remodeling in the lungs that contributes to the irreversible deposition of extracellular matrix (ECM) proteins. Myofibroblasts that accumulate at the site of injury are thought to be the key drivers of ECM deposition and are often associated in the disease. Although it is poorly understood how these immune cells differentiate in the lung, one hypothesis suggests the role of alternatively activated profibrotic macrophages in this process. The data presented in this thesis suggest that there are a presence of UPR and macrophage proteins in the lungs of IPF patients and the UPR may be necessary in the polarization of alternatively activated macrophages. / Thesis / Master of Science (MSc)