Translating the past: an analysis of Beowulf's reception history through the figures of Grendel and Grendel's mother

Since the nineteenth century, Beowulf has received sustained critical attention in the form of scholarship, translation, and adaptation. The figures of Grendel and Grendel’s mother have been presented to us in various forms throughout the last two hundred years, ranging from demonic ogres and witches (in H. E. Marshall’s Stories of Beowulf Told to the Children) to misunderstood and emotionally complex beings (in Parke Godwin’s The Tower of Beowulf). This thesis argues that there is no understanding or perception of Grendel and Grendel’s mother, by either scholars or general readers alike, that has not been intricately shaped by the images and language of these “rewritings”, to use André Lefevere’s term. As with all translations and adaptations, these rewritings are “haunted at all times by their adapted texts” (Hutcheon 6), but, as I argue in this study, they are also haunted by any number of adapted texts (and intertexts) which have preceded them. They are not texts in the second degree, as Linda Hutcheon claims, but rather texts in the nth degree, created and received in relation to any number of prior texts, in variations as diverse as their readers. Beginning with an analysis of numerous Old English terms and contextual information used to describe Grendel and Grendel’s mother, the first chapter of this thesis reconsiders how an Anglo-Saxon audience may have understood the Grendel-kin. By employing a philological and comparative linguistic approach to these descriptive terms, this chapter attempts to form as objective as possible an understanding of these characters, an imperative process if we are to critically examine translations of the text. My research also explores the effects of cultural context on translations and adaptations of Beowulf, recognising them as products of a particular time and space in society. Monstrous figures reflect back to us our own cultural fears, anxieties, and desires, and it is through the various receptions, variations, and constructions of Grendel and Grendel’s mother that these concerns can be best identified

Characterization of Parkin, Tau, and Zinc Interactions with the Microtubule Network

The microtubule cytoskeleton is essential for regulation of cell morphology, trafficking within the cell and cell cycle progression. These diverse functions involve complex microtubule dynamics and the interaction of microtubule-associated proteins (MAPs), molecular motors, and various small ligands. Here we investigate three distinct aspects of microtubule activity: the interactions of microtubules with parkin and tau which may be involved in Parkinson's disease and Alzheimer's disease, respectively, and effects on microtubule stability in prostate cancer. Autosomal Recessive Juvenile Parkinson's disease (ARJP) is a degenerative disorder of the central nervous system. Over 50% of ARJP cases result from mutations that occur within the PARK2 gene that encodes the protein parkin. Recent evidence has suggested that parkin binds to microtubules and can stabilize microtubules against depolymerization. Visualization of the parkin-tubulin complex would help us understand the mechanism of this interaction and provide insights on the role of parkin in the cell. Parkin was expressed, purified and used to decorate microtubules for cryo-electron microscopy. Fourier transforms of images suggest that parkin binds specifically to the tubulin dimer. Further cryo microscopy of the interaction of parkin with microtubules will help define the etiology of ARJP and may reveal novel targets of therapeutic intervention. Hyperphosphorylation of the microtubule-associated protein tau results in a pathological form of the protein found in plaques of patients with Alzheimers disease. Our work has been focused on clarification of the two current models proposed for tau binding along the outside and the inside of the microtubule.Microtubule networks are also clinically important as targets of many chemotherapeutic drugs. Prostate cancer is commonly treated with the microtubule-targeted drug paclitaxel (taxol). A previous report indicated that supplemental zinc sensitized prostate cancer cells to taxol-induced apoptosis, suggesting that increased zinc levels might affect taxol efficacy. We tested taxol's effect in two prostate cancer cell lines maintained under moderately zinc deficient conditions. Taxol-induced apoptosis was reduced in LNCaP cells from zinc-deficient conditions. The IC50 for paclitaxel-induced cell cycle arrest was higher in LNCaP cells. Extracellular zinc levels were thus shown to be an important factor in paclitaxel activity in a prostate cell cancer line

Meiosis-specific Failure of Cell Cycle Progression in Fission Yeast by Mutation of a Conserved β-Tubulin Residue

The microtubule cytoskeleton is involved in regulation of cell morphology, differentiation, and cell cycle progression. Precisely controlled dynamic properties are required for these microtubule functions. To better understand how tubulin's dynamics are embedded in its primary sequence, we investigated in vivo the consequences of altering a single, highly conserved residue in β-tubulin that lies at the interface between two structural domains. The residue differs between the cold-adapted Antarctic fish and temperate animals in a manner that suggests a role in microtubule stability. Fungi, like the Antarctic fish, have a phenylalanine in this position, whereas essentially all other animals have tyrosine. We mutated the corresponding residue in fission yeast to tyrosine. Temperature effects were subtle, but time-lapse microscopy of microtubule dynamics revealed reduced depolymerization rates and increased stability. Mitotic exit signaled by breakdown of the mitotic spindle was delayed. In meiosis, microtubules displayed prolonged contact to the cell cortex during horsetail movement, followed by completion of meiosis I but frequent asymmetric failure of meiosis II spindle formation. Our results indicate that depolymerization dynamics modulated through interdomain motion may be important for regulating a subset of plus-end microtubule complexes in Schizosaccharomyces pombe

Factors that Influence the Formation and Stability of Thin, Cryo-EM Specimens.

Poor consistency of the ice thickness from one area of a cryo-electron microscope (cryo-EM) specimen grid to another, from one grid to the next, and from one type of specimen to another, motivates a reconsideration of how to best prepare suitably thin specimens. Here we first review the three related topics of wetting, thinning, and stability against dewetting of aqueous films spread over a hydrophilic substrate. We then suggest that the importance of there being a surfactant monolayer at the air-water interface of thin, cryo-EM specimens has been largely underappreciated. In fact, a surfactant layer (of uncontrolled composition and surface pressure) can hardly be avoided during standard cryo-EM specimen preparation. We thus suggest that better control over the composition and properties of the surfactant layer may result in more reliable production of cryo-EM specimens with the desired thickness

Characterization, comparison, and optimization of lattice light sheets

Lattice light sheet microscopy excels at the noninvasive imaging of three-dimensional (3D) dynamic processes at high spatiotemporal resolution within cells and developing embryos. Recently, several papers have called into question the performance of lattice light sheets relative to the Gaussian sheets most common in light sheet microscopy. Here, we undertake a theoretical and experimental analysis of various forms of light sheet microscopy, which demonstrates and explains why lattice light sheets provide substantial improvements in resolution and photobleaching reduction. The analysis provides a procedure to select the correct light sheet for a desired experiment and specifies the processing that maximizes the use of all fluorescence generated within the light sheet excitation envelope for optimal resolution while minimizing image artifacts and photodamage. We also introduce a new type of "harmonic balanced" lattice light sheet that improves performance at all spatial frequencies within its 3D resolution limits and maintains this performance over lengthened propagation distances allowing for expanded fields of view

Cytoskeletal organization in microtentacles.

Microtentacles are thin, flexible cell protrusions that have recently been described and whose presence enhances efficient attachment of circulating cells. They are found on circulating tumor cells and can be induced on a wide range of breast cancer cell lines, where they are promoted by factors that either stabilize microtubules or destabilize the actin cytoskeleton. Evidence suggests that they are relevant to the metastatic spread of cancer, so understanding their structure and formation may lead to useful therapies. Microtentacles are formed by microtubules and contain vimentin intermediate filaments, but beyond this, there is little information about their ultrastructure. We have used electron microscopy of high pressure frozen sections and tomography of cryo-prepared intact cells, along with super resolution fluorescence microscopy, to provide the first ultrastructural insights into microtubule and intermediate filament arrangement within microtentacles. By scanning electron microscopy it was seen that microtentacles form within minutes of addition of drugs that stabilize microtubules and destabilize actin filaments. Mature microtentacles were found to be well below one micrometer in diameter, tapering gradually to below 100nm at the distal ends. They also contained frequent branches and bulges suggestive of heterogeneous internal structure. Super resolution fluorescence microscopy and examination of sectioned samples showed that the microtubules and intermediate filaments can occupy different areas within the microtentacles, rather than interacting intimately as had been expected. Cryo-electron tomography of thin regions of microtentacles revealed densely packed microtubules and absence of intermediate filaments. The number of microtubules ranged from several dozen in some areas to just a few in the thinnest regions, with none of the regular arrangement found in axonemes. Improved understanding of the mechanism of microtentacle formation, as well as the resultant structure, will be valuable in developing therapies against metastasis, if the hypothesized role of microtentacles in metastasis is confirmed. This work provides a significant step in this direction