351 research outputs found
CRISPR interference : a structural perspective
No full textThis article was made open access through BIS OA funding. The laboratory is funded by grants from the Biotechnology and Biological Sciences Research Council (BBSRC).CRISPR (cluster of regularly interspaced palindromic repeats) is a prokaryotic adaptive defence system, providing immunity against mobile genetic elements such as viruses. Genomically encoded crRNA (CRISPR RNA) is used by Cas (CRISPR-associated) proteins to target and subsequently degrade nucleic acids of invading entities in a sequence-dependent manner. The process is known as ‘interference’. In the present review we cover recent progress on the structural biology of the CRISPR/Cas system, focusing on the Cas proteins and complexes that catalyse crRNA biogenesis and interference. Structural studies have helped in the elucidation of key mechanisms, including the recognition and cleavage of crRNA by the Cas6 and Cas5 proteins, where remarkable diversity at the level of both substrate recognition and catalysis has become apparent. The RNA-binding RAMP (repeat-associated mysterious protein) domain is present in the Cas5, Cas6, Cas7 and Cmr3 protein families and RAMP-like domains are found in Cas2 and Cas10. Structural analysis has also revealed an evolutionary link between the small subunits of the type I and type III-B interference complexes. Future studies of the interference complexes and their constituent components will transform our understanding of the system.Peer reviewe
A sojourn in Paris 1824-25: sex and sociability in the manuscript writings of Anne Lister (1791-1840)
No full textThis thesis examines the day to day practices that constituted Anne Lister's (1791-1840) sexuality and sociability within the range of her writings, as well as her society. Anne's writings were a detailed account, spanning her lifetime, of her own love and relationships with the 'fairer sex' (Whitbread 1988, 145). Anne's sociality, seen in her correspondence and plain handwritten journal entries, has been explored by Muriel Green in Miss Lister of Shibden Hall and Jill Liddington in Female Fortune and Nature's Domain (Green 1992; Liddington 1998; 2003). As a gentlewoman of adequate means, Anne has garnered some attention from women's historians interested in her agency within an early nineteenth century social and historical context. Anne's sexual identity has been extensively analysed over the past nearly twenty years by lesbian feminists, queer theorists, women's historians and historians of sexuality concerned with the history and development of modern Western female homosexuality and gender. The source for theorising Anne's sexuality has been the edited selections of the crypted journal entries, published by Helena Whitbread in I Know My Own Heart and No Priest but Love (Whitbread 1988; 1992). However, many analyses deal either with the theorisation of Anne's sexuality or her sociality; the theoretical difficulty with reconciling these categories has troubled the analysis of her complex subjectivity. Drawing upon the archival materials, I have used an interdisciplinary feminist approach to analyse the sexual and social processes of Anne's everyday interactions in her writings. Taking the seven month period of the sojourn to Paris in 1824-25, I have focused upon Anne's textual practices within her journal volume and letters during her residence in Paris, her social practices with the other guests at the guesthouse 24 Place Vendome and her sexual practices with her lover, the widow Mrs. Maria Barlow. The journal volumes and correspondence are a valuable historical record of one gentlewoman's engagement with early nineteenth century British culture
Judith Summers interview
No full textJudith Anne Summers was born in London, England on May 19th, 1953. She descends from Sephardic and Ashkenazi roots and speaks English, French and Italian. She is a historian, freelance journalist, and author of fiction, nonfiction, biographies and history books. She applied for Portuguese citizenship as a family along with her sister, son and niece.Judith Summers discusses growing up in London and her professional background as a historian, author and freelance journalist. She explains her family's Sephardic origins in the 17th century in Braganza, Portugal and their migration to London's East End which housed a large Jewish community (00:04:36). Judith shares her interest in research and her process for tracing her family lineage from birth/marriage certificates, family interviews, the English census and London Metropolitan Archives (00:10:00). She explains how she learned about the Portuguese citizenship law, her connections with a friend in Porto and the application requrements (00:19:00). Discusses British, European and Jewish identity, motivations for citizenship (00:22:17) and surprises of the application process (00:26:33). Concludes with feelings on Brexit (00:30:45) views on Portuguese citizenship as a privilege and gift to Sephardic Jews, and strengthening ties to Porgual (00:32:45).Topics presented in order of discussion on recording:
-Overview of published work and research topics of interest (history of London, biographies)
-Languages learned and religious upbringing attending a Jewish Reform synagogue.
-Sephardic and Ashkenazi background and migration of paternal Sephardic ancestry from Portugal to London.
-Story about Bevis Marks Synoguge in London and discovery of family names displayed on walls from 1700s.
-Sharing of research process tracing family heritage through birth certificates, marriage certificates, family interviews, English census.
-Awareness of Sephardic identity and traditional foods (stew, chopped liver, smoked salmon) prepared by paternal grandmother
-Learning of Portuguese citizenship law through Sephardic friend.
-Application process- receiving Sephardic recognition from the Porto community and submitting family and criminal record documents.
-Feelings on British and European identity, Brexit and the desire to remain connected to Jewish heritage in Portugal.
-Feelings on expulsions and persecutions of the Inquisition with regards to Portugal today.
-The privilege of Portuguese citizenship and the view that this opportunity is a gift from the Portuguese government to Jewish people.
-Strengthening connections with Portugal as a result of the citizenship law.1 online resourceSephardi Citizenship Oral Histor
Michel Foucault and Judith Butler: troubling Butler's appropriation of Foucault's work
No full textOne of the main influences on Judith Butler‘s thinking has been the work of Michel Foucault. Although this relationship is often commented on, it is rarely discussed in any detail. My thesis makes a contribution in this area. It presents an analysis of Foucault‘s work with the aim of countering Butler‘s representation of his thinking. In the first part of the thesis, I show how Butler initially interprets Foucault‘s project through Nietzschean genealogy, psychoanalysis and Derridean discourse, and how she later develops this interpretation in line with the progress of her own project. In the main part of the thesis, I present an analysis of Foucault‘s thinking in the period from The Archaeology of Knowledge (1969) to The History of Sexuality volume 1 (1976). This analysis focuses on the aspect of his work which has most influenced Butler‘s thinking: namely the notion of a relationship between knowledge, discourse and power. The other issues in his work which Butler addresses—genealogy, the subject, the body, abnormality, and sexuality—are discussed within this framework. I show how, in the early 1970s, Foucault develops the notion of power-knowledge, and sets out a relationship between power-knowledge and discourse which is overlooked by Butler. I argue that Butler interprets Foucaultian power through the notions of repression and social norms, and ignores the concepts of technology and strategy which form a key part of Foucault‘s thinking. I show how, from The Archaeology of Knowledge on, Foucault develops a socio-historical ontology and a genealogy of the subject, both of which are at variance with Butler‘s interpretation of his thinking
'The cracked mirror': Anne Sexton's poetics of self-representation
No full textThis thesis re-evaluates the work of the poet Anne Sexton (1928-1974), concentrating, in particular, on the indeterminacies, contradictions and aporia which it finds to be characteristic of her ostensibly frank and self-revelatory writing. The study is based on a close textual
analysis of Sexton's writing, is informed by oststructuralist theories, and is sustained by an
examination and discussion of archive collections of her previously unpublished papers. In seeking an understanding of Sexton's poetics, the thesis identifies and interrogates the strategies of denial and obfuscation apparent in her own explication of her work - principally, by scrutiny of the unpublished, and previously unresearched, drafts of a series of lectures
which she delivered in 1972. Chapters One and Two consider the origins of `confessional' or - Sexton's preferred term - 'personal' poetry and reassess her place within contemporary poetry. They suggest that
Sexton's writing is engaged in a process of negotiation and contestation, both with the boundaries and expectations of confessionalism, and with the strictures of T. S. Eliot's theory of `impersonality'. In support of these arguments, Chapter Two offer a reading of Sexton's
little-known poem, `Hurry Up Please It's Time', alongside its intertext, Eliot's The Waste Land. Chapter Three reassesses received views of the supposedly beneficial interrelationship between confessional speaker and reader. It examines Sexton's appropriation of dramatic
masks and personae and her use of metaphors of striptease and prostitution, and suggests that these are employed simultaneously to appease and to repel an intrusive audience. Similarly, Chapters Four and Five trace Sexton's problematisation of two previously-accepted tenets of confessional poetry: its status as autobiography and its truthfulness, drawing attention to the techniques employed in order to give the impression of both. Chapter Six considers Sexton's
problematic engagement with a language which is not malleable, transparent, and referential but, rather, is experienced as uncooperative and occlusive. Finally, the thesis recuperates Sexton from the common charge of narcissism, arguing that it is the writing, rather than the poet, which is self-reflexive and self-conscious. In this respect, it concludes that her work - perhaps unexpectedly - anticipates many of the tendencies of postmodernist writing
Depression and Gender: The Expression and Experience of Melancholy in the Eighteenth Century
No full textThis thesis investigates the life and work of six eighteenth-century writers, two male and four female. It explores their experience of depression through their letters and other autobiographical material, and examines the ways in which they represent melancholy in their poetry and prose. The subject of Chapter Two is Thomas Gray, whose real life persona as the lonely intellectual is also identifiable in his poetry. The Scottish poet Robert Fergusson is studied in Chapter Three. Fergusson’s lively and vigorous mind was shattered in the months leading up to his death, during which time some of his writing became darkly nihilistic. Chapter Four looks at Anne Finch, Countess of Winchilsea, a lifelong depressive who often wrote about her feelings of despair in her poetry. Chapter Five explores Lady Mary Wortley Montagu. She was a courageous and controversial figure, but despite her resilience, on occasion in her letters she reveals her vulnerability and susceptibility to low spirits, a mood which is sometimes expressed in her creative writing. Sarah Scott, whose life and work have not yet been considered in relation to the subject of melancholy, is examined in Chapter Six. Her novel includes several low-spirited and depressed female characters who are continually seeking asylum from a hostile world. Chapter Seven analyses Charlotte Smith, a mother of twelve children whose unhappy marriage ended in separation. Smith wrote extensively about her depression in her letters, prefaces, poetry and novels.
This study shows that the women in particular use their writing on melancholy and depression to express their discontent with the confined way in which they are often expected to live out their lives
Moving between worlds : gender, class, politics, sexuality and women's networks in the diaries of Anne Lister of Shibden Hall, Halifax, Yorkshire, 1830-1840.
No full textSIGLEAvailable from British Library Document Supply Centre- DSC:DXN003174 / BLDSC - British Library Document Supply CentreGBUnited Kingdo
'Translated from the Gikuyu by the author' : Ngugi wa Thiong'o's self-translation of Wizard of the Crow
No full textNgugi wa Thiong’o wrote Murogi wa Kagogo in Gikuyu in 2004, and published the English version, Wizard of the Crow, in 2006, announcing on the title page that the novel is ‘A translation from Gikuyu by the author’. The complex interplay of languages in Ngugi’s self-translation is central to understanding the novel for two main reasons. Firstly, Ngugi’s dictator novel depicts the political, economic and social intricacies that have characterised the postcolonial African state and, as stories and realities collapse into one another, the reader realises that the eponymous Wizard of the Crow is the embodiment of the writer in postcolonial society. Consequently, the play of languages in the text raises questions about the role of the writer in the face of dictatorship. Secondly, the reader is invited to question the status of the translated text in light of Ngugi’s advocacy of writing in indigenous languages. The author of a literary work must first make a choice of language and then consider how the language will be used. When that work is, in turn, translated, this raises another set of questions about the status of the text, as well as the status of the translation. My interest here then, is not in the similarities or dissimilarities between Murogi wa Kagogo and the English version, but instead Ngugi’s preoccupation with the question of language in Wizard of the Crow and the text’s critical status as self-translation
The cave: A search for the mother’s story in narrative literature
No full textThe mother’s voice is underrepresented in literature. The mother has been a silent figure, always present, often near, featuring in the story of another, but rarely the focus of the story. She has been spoken for, about and around, but rarely empowered to speak for herself.
In this thesis I argue that the mother’s story, in narrative fiction and memoir, should be available, and culturally valued. Since the diversity of women’s experiences of mothering cannot be explained by any single theory or ideology, narrative may articulate the complexities and ambiguities experienced in motherhood in ways that scholarly discourses do not always allow.
This thesis includes a creative component—a collection of related fictional stories narrated by one mother, and entitled “The Cave”. Adopting the concept of the cave, as a metaphor for the transformative potential of mothering, the fiction draws on the mundane, everyday experiences of a life that is centred on caring for children. The exegesis that follows is based on three approaches to mothering narratives: their research, reading and writing. It explores the emergence of the mother’s story within theoretical discourses around motherhood, and its more recent appearances in fiction and non-fiction narratives. It suggests reasons for the absence of the mother’s subjective voice, argues that women have been disadvantaged by this silence, and seeks new possibilities for representing the complexity of mothering experiences
Structure of the archaeal Cascade subunit Csa5 : Relating the small subunits of CRISPR effector complexes
No full textThis work was funded by a grant from the Biotechnology and Biological Sciences Research Council (BBSRC) (REF: BB/G011400/1) to M.F.W. and J.H.N. and a BBSRC-funded studentship to J.R.The Cascade complex for CRISPR-mediated antiviral immunity uses CRISPR RNA (crRNA) to target invading DNA species from mobile elements such as viruses, leading to their destruction. The core of the Cascade effector complex consists of the Cas5 and Cas7 subunits, which are widely conserved in prokaryotes. Cas7 binds crRNA and forms the helical backbone of Cascade. Many archaea encode a version of the Cascade complex (denoted Type I-A) that includes a Csa5 (or small) subunit, which interacts weakly with the core proteins. Here, we report the crystal structure of the Csa5 protein from Sulfolobus solfataricus. Csa5 comprises a conserved α-helical domain with a small insertion consisting of a weakly conserved β-strand domain. In the crystal, the Csa5 monomers have multimerized into infinite helical threads. At each interface is a strictly conserved intersubunit salt bridge, deletion of which disrupts multimerization. Structural analysis indicates a shared evolutionary history among the small subunits of the CRISPR effector complexes. The same α-helical domain is found in the C-terminal domain of Cse2 (from Type I-E Cascade), while the N-terminal domain of Cse2 is found in Cmr5 of the CMR (Type III-B) effector complex. As Cmr5 shares no match with Csa5, two possibilities present themselves: selective domain loss from an ancestral Cse2 to create two new subfamilies or domain fusion of two separate families to create a new Cse2 family. A definitive answer awaits structural studies of further small subunits from other CRISPR effector complexes.Peer reviewe
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