Activation of Akt/PKB, increased phosphorylation of Akt substrates and loss and altered distribution of Akt and PTEN are features of Alzheimer's disease pathology

Studies suggest that activation of phosphoinositide 3-kinase-Akt may protect against neuronal cell death in Alzheimer's disease (AD). Here, however, we provide evidence of increased Akt activation, and hyperphosphorylation of critical Akt substrates in AD brain, which link to AD pathogenesis, suggesting that treatments aiming to activate the pathway in AD need to be considered carefully. A different distribution of Akt and phospho-Akt was detected in AD temporal cortex neurons compared with control neurons, with increased levels of active phosphorylated-Akt in particulate fractions, and significant decreases in Akt levels in AD cytosolic fractions, causing increased activation of Akt (phosphorylated-Akt/total Akt ratio) in AD. In concordance, significant increases in the levels of phosphorylation of total Akt substrates, including: GSK3ßSer9, tauSer214, mTORSer2448, and decreased levels of the Akt target, p27kip1, were found in AD temporal cortex compared with controls. A significant loss and altered distribution of the major negative regulator of Akt, PTEN (phosphatase and tensin homologue deleted on chromosome 10), was also detected in AD neurons. Loss of phosphorylated-Akt and PTEN-containing neurons were found in hippocampal CA1 at end stages of AD. Taken together, these results support a potential role for aberrant control of Akt and PTEN signalling in AD.

Facile Syntheses of Three Major Metabolites of Thioridazine

NMR studies were conducted with the aim of determining the diastereoisomeric ratio of a commercially supplied sample of mesoridazine (MES) and to compare the results with a freshly synthesised sample of MES. The results indicated that the commercially supplied MES consisted almost entirely of one diastereoisomeric pair, which was in agreement with previous findings reported by Eap et al. (J Chromatogr 669:271-279, 1995). The synthesised sample of MES was analysed by NMR in two stages: 1) as the initial product isolated as the free base from the direct synthesis, and 2) as the free base isolated from the crystallised besylate salt of the synthetic product. The NMR results show that the initial synthetic product consisted of two equal pairs of diastereoisomers. The diastereoisomeric pairs were further separated by the addition of the chiral shift reagent (R)-(-)-N-(3,5 dinitrobenzoyl)-alpha-benzylamine to reveal equal quantities of all four enantiomers, clearly observed at the methyl sulfoxide proton peak of the NMR scan. The sample obtained from the crystallisation of MES besylate, however, indicated a significant difference, with a diastereoisomeric ratio of 75:25. The results suggest that MES besylate undergoes preferential crystallisation of one pair of diastereoisomers, with the other pair remaining in solution. (C) 2004 Wiley-Liss, Inc.

'Resolve me of all ambiguities': Doctor Faustus and the Failure to Unify

http://extra.shu.ac.uk/emls/si-16/duxfdrfs.htm

Tongue-tied?: An Active Analysis of Brian Friel's Translations

This article has arisen from a research-led production of Translations by Brian Friel for Queen’s University’s Tyrone Guthrie Society in February 2010. Drawing partly on a review of the existing critical literature and also from questions left unresolved by a previous experience of directing the play, the production sought to address through ‘active analysis’ (Merlin 2001) a number of research questions relating to the embodied nature of the rehearsal process and the historicity of Friel’s play. The analysis invokes Bergson (1910), Lefebvre (1991) and Worthern (2006) in establishing a performative correlative for insightful but more literary studies by Connolly (1993), Lojek (1994) and McGrath (1989 & 1999). A detailed account of the rehearsal process helps reveal the extent to which the idea of failure of communication is embedded in the text and embodied in performance, while an experiment with the partial use of the Irish language casts further light on Friel’s extraordinary device of rendering two languages through the medium of one. The use of music to counterpoint, rather than underscore the action, together with an achronological sequence of projected historical images inspired by Andrews (1983) provided me as director a means to challenge the audience’s presuppositions about the play. The sense of palimpsest, of the layered histories, that this evoked also served to highlight Friel’s use of the wider stylistic palette of Anglo-Irish drama, revealing Translations as a forerunner for Stewart Parker’s more explicit formal experiments in Northern Star. In rehearsal and performance Friel’s place in the continuum of the Irish theatrical canon became clear, as stylistic allusions to O’Casey, Shaw, Wilde and Beckett were embodied by the actors on the rehearsal room floor.

Mapping Medieval Geographies: Geographical Encounters in the Latin West and Beyond, 300–1600

'Mapping Medieval Geographies' explores the ways in which geographical knowledge, ideas and traditions were formed in Europe during the Middle Ages. Leading scholars reveal the connections between Islamic, Christian, Biblical, and Classical geographical traditions from Antiquity to the later Middle Ages and Renaissance. The book is divided into two parts: Part I focuses on the notion of geographical tradition and charts the evolution of celestial and earthly geography in terms of its intellectual, visual and textual representations; whilst Part II explores geographical imaginations; that is to say, those 'imagined geographies' that came into being as a result of everyday spatial and spiritual experience. Bringing together approaches from art, literary studies, intellectual history and historical geography, this pioneering volume will be essential reading for scholars concerned with visual and textual modes of geographical representation and transmission, as well as the spaces and places of knowledge creation and consumption.

Re-Visiting Sylvia Townsend Warner

Sylvia Townsend Warner was born in 1893 in Harrow and died in Dorset in 1978. Her writing career was both productive and diverse, spanning poems, short stories, novels, music reviews, a biography, translations of Proust, and a guide to Somerset. But this list, impressive as it is, does not do justice to the idiosyncrasy and heterogeneity of her work. While she is well known mostly for the seven novels she published, those works are all radically different in style and content. Indeed, Townsend Warner's singularity has, it could be argued, made it difficult to place her in the various fields and sub-fields of 20th-century literary studies. She shares as many similarities as differences with the high modernists who dominated the literary landscape of the interwar period. Likewise she fits, yet also resists, the more recent formulations of intermodernist and middlebrow scholarship that have attempted to interrogate and expand the horizons of mid-20th century literature.

Mixed Messages: American Correspondences in Visual and Verbal Practices

Mixed Messages presents and interrogates ten distinct moments from the arts of nineteenth, twentieth and twenty-first century America where visual and verbal forms blend and clash. Charting correspondences concerned with the expression and meaning of human experience, this volume moves beyond standard interdisciplinary theoretical approaches to consider the written and visual artwork in embodied, cognitive, and contextual terms.

Offering a genuinely interdisciplinary contribution to the intersecting fields of art history, avant-garde studies, word-image relations, and literary studies, Mixed Messages takes in architecture, notebooks, poetry, painting, conceptual art, contemporary art, comic books, photographs and installations, ending with a speculative conclusion on the role of the body in the experience of digital mixed media. Each of the ten case studies explores the juxtaposition of visual and verbal forms in a manner that moves away from treating verbal and visual symbols as operating in binary or oppositional systems, and towards a consideration of mixed media, multi-media and intermedia work as brought together in acts of creation, exhibition, reading, viewing, and immersion. The collection advances research into embodiment theory, affect, pragmatist aesthetics, as well as into the continuing legacy of romanticism and of dada, conceptual art and surrealism in an American context.

Andrew Marvell's Latin Poetry: From Text to Context (356pp.)

David Norbrook, Review of English Studies 56 (Sept. 2005), 675-6.
‘We have waited a long time for a study of Marvell’s Latin poetry; fortunately, Estelle Haan’s monograph generously makes good the loss ... One of her most intriguing suggestions … is that Marvell may have presented paired poems like ‘Ros’ and ‘On a Drop of Dew’, and the poems to the obligingly named Dr Witty, to his student Maria Fairfax as his own patterns for the pedagogical practice of double translation. Perhaps the most original parts of the book, however, move beyond the familiar canon to cover the generic range of the Latin verse. Haan offers a very full contextualization of the early Horatian Ode to Charles I in seventeenth-century exercises in parodia. In a rewarding reading of the poem to Dr Ingelo she shows how Marvell deploys the language of Ovid’s Tristia to present Sweden as a place of shivering exile, only to subvert this model with a neo-Virgilian celebration of Christina as a virtuous, city-building Dido. She draws extensively on historical as well as literary sources to offer very detailed contextualizations of the poem to Maniban and ‘Scaevola Scotto-Britannus’... This monograph opens up many new ways into the Latin verse, not least because it is rounded off with new texts and prose translations of the Latin poems. These make a substantial contribution in their own right. They are the best and most accurate translations to date (those in Smith’s edition having some lapses); they avoid poeticisms but bring out the structure of the poems' wordplay very clearly. This book brings us a lot closer to seeing Marvell whole.'

Vergilius Redivivus: Studies in Joseph Addison's Latin Poetry

J.W. Binns, Modern Language Review 101.2 (2006), 504-5:
‘This book is an important contribution to the study of Anglo-Latin poetry in the late seventeenth and early eighteenth centuries … ’Haan provides an able and authoritative account …, setting the poems in their contexts, and providing for each a very clear and penetrating analysis which traces the classical well-springs that lie behind much of Addison’s Latin writing, and also calls attention to non-traditional elements’.