495 research outputs found
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“An appreciative and grateful author”: Edith Wharton and the House of Macmillan
This essay is the first piece of scholarship to examine the relationship between the expatriate American novelist Edith Wharton (1862-1937) and her chief British publisher, Macmillan and Co. Entirely original analysis draws extensively upon the author/publisher correspondence held in the Macmillan Archive in the British Library, and challenges existing readings of the firm's handling of women novelists in the period 1900-1930
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[Book Review] Alaistair Fowler, <i>The Mind of the Book: Pictorial Title Pages</i>
A review of Fowler, Alastair, The Mind of the Book: Pictorial Title Pages (Oxford: OUP, 2017), ISBN 978-0-0190871766-9
Allotopic RNA expression strategy to rescue an endogenous mitochondrial ATP6[1] mutation in Drosophila
Mitochondria are essential organelles in the cell. One of their most critical functions is the generation of cellular energy in the form of ATP. The presence of DNA in the mitochondrial matrix makes this organelle semi-autonomous. However, it relies heavily on the nucleus and cytosol to import ~99% of its proteins and some RNA molecules for its normal functioning. Mutations in the mitochondrial DNA (mtDNA) cause several devastating disorders. Due to their complexity and our incomplete understanding of mitochondrial disease pathogenesis, these disorders are difficult to diagnose and currently no pharmacological treatment exists. Further, gene therapy for these devastating disorders is impeded due to lack of mitochondrial genome manipulation techniques. Understanding the mechanism of pathogenesis and developing mtDNA manipulation strategies are key to developing remedial therapies.
In my thesis, I investigated an RNA allotopic strategy of targeting RNA into the mitochondria in vivo in flies. In my first aim, I improved an in vivo mitochondrial-targeting tool (mtTRES vector) to manipulate proteins encoded by the mitochondrial DNA. This vector integrates into the nuclear genome and results in the transcription of a chimeric RNA consisting of a mitochondrial targeting signal sequence and a small non-coding antisense RNA.
Previous studies have attempted allotopic expression via both protein and RNA import with mixed results. Only a few of them, however, have been tested in vivo and none have been examined for rescue in an animal model of mitochondrial disease. Since our lab has a well characterized mtDNA mutation fly model, ATP6[1], I had a unique opportunity to investigate rescue strategies in these models. In my second aim, I improved a unique set of mtTRESPro vectors for both flies and humans to target long coding RNAs into mitochondria. Once imported these long RNAs are designed to be endogenously translated in mitochondria. By targeting a wild type copy of the mutant ATP6 gene, I explored the rescuing potential of allotopic RNA import in vivo. Our data suggest the mtTRES and mtTRESPro mitochondrial manipulation tools have genuine potential to be developed into a mitochondrial disease gene therapy
NASA space and Earth science data on CD-ROM
The National Space Science Data Center (NSSDC) is very interested in facilitating the widest possible use of the scientific data acquired through NASA spaceflight missions. Therefore, NSSDC has participated with projects and data management elements throughout the NASA science environment in the creation, archiving, and dissemination of data using Compact Disk-Read Only Memory (CD-ROM). This CD-ROM technology has the potential to enable the dissemination of very large data volumes at very low prices to a great many researchers, students and their teachers, and others. This catalog identifies and describes the scientific CD-ROM's now available from NSSDC including the following data sets: Einstein Observatory CD-ROM, Galileo Cruise Imaging on CD-ROM, International Halley Watch, IRAS Sky Survey Atlas, Infrared Thermal Mapper (IRTM), Magellan (MIDR), Magellan (ARCDR's), Magellan (GxDR's), Mars Digital Image Map (MDIM), Outer Planets Fields & Particles Data, Pre-Magellan, Selected Astronomical Catalogs, TOMS Gridded Ozone Data, TOMS Ozone Image Data, TOMS Update, Viking Orbiter Images of Mars, and Voyager Image
Readers and Reading in the First World War
This essay consists of three individually authored and interlinked sections. In ‘A Digital Humanities Approach’, Francesca Benatti looks at datasets and databases (including the UK Reading Experience Database) and shows how a systematic, macro-analytical use of digital humanities tools and resources might yield answers to some key questions about reading in the First World War. In ‘Reading behind the Wire in the First World War’ Edmund G. C. King scrutinizes the reading practices and preferences of Allied prisoners of war in Mainz, showing that reading circumscribed by the contingencies of a prison camp created an unique literary community, whose legacy can be traced through their literary output after the war. In ‘Book-hunger in Salonika’, Shafquat Towheed examines the record of a single reader in a specific and fairly static frontline, and argues that in the case of the Salonika campaign, reading communities emerged in close proximity to existing centres of print culture. The focus of this essay moves from the general to the particular, from the scoping of large datasets, to the analyses of identified readers within a specific geographical and temporal space. The authors engage with the wider issues and problems of recovering, interpreting, visualizing, narrating, and representing readers in the First World War
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An Examination of Bookshelves in the Age of the COVID-19 Pandemic as a “Liminal Space”
In the space of a few weeks in 2020, the rapid spread of the COVID-19 virus into a global pandemic has changed the way we work, live, interact and communicate with one another. One highly unexpected result of the massive rise in homeworking has been an extraordinary exposure of domestic bookshelves, which in the famous words of Amanda Hess, have become the “quarantine’s hottest accessory” (New York Times, May 1, 2020). Personal bookshelves had hitherto been jealously guarded, a marker for personal taste and shared only with the select few invited into their owners’ households and allowed to scan the titles on display. This physically delimited space has now been unleashed upon the world: where once few people could look at the books on our shelves, now theoretically, almost everyone can. The pandemic bookshelf has accidently been fashioned into the most ubiquitous liminal zone anywhere: it is the ostensibly private and personal backdrop for the staging of our public, digitally mediated, professional existence. Drawing upon theoretical perspectives from anthropology, psychology and literary theory, this chapter explores the many ways in which the private-public bookshelf has become the cultural liminal space par excellence during the COVID-19 pandemic
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Reusing Historical Questionnaire Data and Using Newly Commissioned Oral History Interviews as Evidence in the History of Reading
Interviews, whether freestyle or structured, printed or recorded, offer historians of reading valuable insights into the practices and preferences of individual readers. Despite the potential biases that can be generated by the interview format, the reshaping of memory through the process of retelling, and the questions that can go unasked (and therefore, unanswered), the individual interview can be a richly textured source of information for historians of reading. In this article, three researchers involved in both the recently completed Reading Communities: Connecting the Past and the Present project and the ongoing historically focussed UK Reading Experience Database, 1450-1945 project (UK-RED) examine the ways in which interviews can capture individual records of reading, both in the past and the present
Severe acute respiratory syndrome coronavirus 3a protein activates the mitochondrial death pathway through p38 MAP kinase activation
The molecular mechanisms governing severe acute respiratory syndrome coronavirus-induced pathology are not fully understood. Virus infection and some individual viral proteins, including the 3a protein, induce apoptosis. However, the cellular targets leading to 3a protein-mediated apoptosis have not been fully characterized. This study showed that the 3a protein modulates the mitochondrial death pathway in two possible ways. Activation of caspase-8 through extrinsic signal(s) caused Bid activation. In the intrinsic pathway, there was activation of caspase-9 and cytochrome c release from the mitochondria. This was the result of increased Bax oligomerization and higher levels of p53 in 3a protein-expressing cells, which depended on the activation of p38 MAP kinase (MAPK) in these cells. For p38 activation and apoptosis induction, the 3a cytoplasmic domain was sufficient. In direct Annexin V staining assays, the 3a protein-expressing cells showed increased apoptosis that was attenuated with the p38 MAPK inhibitor SB203580. A block in nuclear translocation of the STAT3 transcription factor in cells expressing the 3a protein was also observed. These results have been used to present a model of 3a-mediated apoptosis
Highly efficient 5\u27 capping of mitochondrial RNA with NAD+ and NADH by yeast and human mitochondrial RNA polymerase
Bacterial and eukaryotic nuclear RNA polymerases (RNAPs) cap RNA with the oxidized and reduced forms of the metabolic effector nicotinamide adenine dinucleotide, NAD+ and NADH, using NAD+ and NADH as non-canonical initiating nucleotides for transcription initiation. Here, we show that mitochondrial RNAPs (mtRNAPs) cap RNA with NAD+ and NADH, and do so more efficiently than nuclear RNAPs. Direct quantitation of NAD+- and NADH-capped RNA demonstrates remarkably high levels of capping in vivo: up to ~60% NAD+ and NADH capping of yeast mitochondrial transcripts, and up to ~15% NAD+ capping of human mitochondrial transcripts. The capping efficiency is determined by promoter sequence at, and upstream of, the transcription start site and, in yeast and human cells, by intracellular NAD+ and NADH levels. Our findings indicate mtRNAPs serve as both sensors and actuators in coupling cellular metabolism to mitochondrial transcriptional outputs, sensing NAD+ and NADH levels and adjusting transcriptional outputs accordingly. © 2018, Bird et al
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Introduction
The introduction provides an overview of the main issues informing current analysis of bookshelves during the COVID-19 pandemic. It starts by sketching out some of the main theoretical frameworks relevant to investigating the cultural phenomenon of bookshelves in the pandemic. It then surveys trends in pandemic reading and the rise of bibliotherapy since the start of the pandemic, before examining the ways in which lockdown induced home working has blurred the boundaries between private and public spheres. This is followed by a detailed discussion of the bookshelf as a construct of global neoliberalism which draws attention to increasing socioeconomic inequality, both between the Global North and the Global South, and within individual nation states. The introduction then outlines the contents of the volume with brief precis of the 12 chapters; summarizes areas of investigation not covered in the volume; and finishes by gesturing to research questions and issues for future consideration
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