Glycogen synthase kinase 3 (GSK3) in the heart: a point of integration in hypertrophic signalling and a therapeutic target? A critical analysis

Glycogen synthase kinase 3 (GSK3, of which there are two isoforms, GSK3alpha and GSK3beta) was originally characterized in the context of regulation of glycogen metabolism, though it is now known to regulate many other cellular processes. Phosphorylation of GSK3alpha(Ser21) and GSK3beta(Ser9) inhibits their activity. In the heart, emphasis has been placed particularly on GSK3beta, rather than GSK3alpha. Importantly, catalytically-active GSK3 generally restrains gene expression and, in the heart, catalytically-active GSK3 has been implicated in anti-hypertrophic signalling. Inhibition of GSK3 results in changes in the activities of transcription and translation factors in the heart and promotes hypertrophic responses, and it is generally assumed that signal transduction from hypertrophic stimuli to GSK3 passes primarily through protein kinase B/Akt (PKB/Akt). However, recent data suggest that the situation is far more complex. We review evidence pertaining to the role of GSK3 in the myocardium and discuss effects of genetic manipulation of GSK3 activity in vivo. We also discuss the signalling pathways potentially regulating GSK3 activity and propose that, depending on the stimulus, phosphorylation of GSK3 is independent of PKB/Akt. Potential GSK3 substrates studied in relation to myocardial hypertrophy include nuclear factors of activated T cells, beta-catenin, GATA4, myocardin, CREB, and eukaryotic initiation factor 2Bvarepsilon. These and other transcription factor substrates putatively important in the heart are considered. We discuss whether cardiac pathologies could be treated by therapeutic intervention at the GSK3 level but conclude that any intervention would be premature without greater understanding of the precise role of GSK3 in cardiac processes.

Going global: the Brazilian scripted film

This article departs from the assumption that a certain section of world cinema, usually defined as ‘independent’, has been evolving on the basis of good scripts. Between the late 1980s and early 90s, there has been a boom of new cinemas in the world, such as the new Iranian, Taiwanese, Japanese, Mexican, Argentine and Brazilian cinemas. A significant part of this production shows a renewed interest in local and national peculiarities of their respective countries, going against the grain of globalisation and its typical cultural dilution. Most of these films are also engaged in reassessing narrative cinema, as a kind of reaction against the deconstructive work carried out by postmodern cinema of the 1980s.Recent new cinemas are supported by a combination of local and international resources, derived from public and private sponsors at home, and funding agencies, festivals and TV channels abroad. In most cases funds are granted after the film script has been analysed and approved by commissions of experts. The New Brazilian Cinema, or cinema da retomada as it is locally called, has been enormously affected by this scheme, which has even caused a ‘script boom’ in Brazil in the past decade. The chapter examins the results of this process.

Eye candy for the blind: re-introducing Lyotard's Acinema into discourses on excess, motion and spectacle in contemporary Hollywood

Jean-François Lyotard's 1973 essay ‘Acinema’ is explicitly concerned with the cinematic medium, but has received scant critical attention. Lyotard's acinema conceives of an experimental, excessive form of film-making that uses stillness and movement to shift away from the orderly process of meaning-making within mainstream cinema. What motivates this present paper is a striking link between Lyotard's writing and contemporary Hollywood production; both are concerned with a sense of excess, especially within moments of motion. Using Charlie's Angels (McG, 2000) as a case study – a film that has been critically dismissed as ‘eye candy for the blind’ – my methodology brings together two different discourses, high culture theory and mainstream film-making, to test out and propose the value of Lyotard's ideas for the study of contemporary film. Combining close textual analysis and engagement with key scholarship on film spectacle, I reflexively engage with the process of film analysis and re-direct attention to a neglected essay by a major theorist, in order to stimulate further engagement with his work.

Spectroscopic signatures of an Fmoc–tetrapeptide, Fmoc and fluorene

The hydrophobic Fmoc [N-(fluorenyl)-9-methoxycarbonyl] unit is often conjugated to peptides to confer amphiphilicity on the molecules, and to introduce the potential for aromatic stacking interactions. In this paper we report spectroscopic data for fluorene, Fmoc and Fmoc conjugated to a small peptide (GRDS in this case) to enable interpretation of spectroscopic data collected on complex structures that can be created with Fmoc–peptide molecules. We report absorbance data (ultra violet and infrared), circular dichroism, linear dichroism (both film and Couette flow orientation) and Raman spectra. Orientations of the Fmoc chromophores in the linear dichroism studies are deduced.

Isotype: design and contexts 1925–1971

The work in graphic communication carried out by Otto Neurath and his associates – now commonly known simply as Isotype – has been the subject of much interest in recent years. Conceived and developed in the 1920s as ‘the Vienna method of pictorial statistics’, this approach to designing information had from its inception the power to grow and spread internationally. Political developments in Europe played their part in its development, and production moved to the Netherlands (1934) and to England (1940), where the Isotype Institute continued to produce work until 1971. Bringing together the latest research, this book is the first comprehensive, detailed account of its subject. The Austrian, Dutch, and English years of Isotype are described here freshly and extensively. There are chapters on the notable extensions of Isotype to Soviet Russia, the USA, and Africa. Isotype work in film and in designing for children is fully documented and discussed. Between these main chapters the book presents interludes documenting Isotype production visually. Three appendices reprint key documents. In its international coverage and its extensions into the wider terrain of history, this book opens a new vista in graphic design.

Chaos, culture and fantasy: The television plays of Howard Schuman

The single plays of American ex-pat playwright Howard Schuman produced for British television between 1973 and 1983 have received little critical attention. Written in a distinctly un-British madcap, non-naturalistic and often pulpy 'B movie' style, they centre around caricatured, hysterical and/or camp characters and make frequent references to popular culture. This article provides a general survey of Schuman's plays and analyses his sensibility as a screenwriter, drawing extensively on material from interviews with the writer. The article's particular focus is how and why different cultural forms including music, film and theatre are used and referred to in Schuman's plays, and how this conditions the plays' narrative content and visual and aural form. It also considers the reception of Schuman's plays and their status as non-naturalistic dramas that engage heavily with American pop culture, within the context of British drama. Finally, it explores the writer's relationship to style and aesthetics, and considers how his written works have been enhanced through creative design decisions, comparing his directions (in one of his scripts) with the realized play to reflect on the use of key devices.

“There’s something very familiar about all this”: generic play and performance in the Back to the Future trilogy (Robert Zemeckis, 1985, 1989, 1990)

The Back to the Future Trilogy incorporates several different generic elements, including aspects of the fifties teen movie, science fiction, comedy and the western. These different modes playfully intertwine with each other creating a complex world of repetitions, echoes and modulations. This essay seeks to interrogate the construction of generic elements and the play between them through a close analysis of a repeated performance. Genre is signalled through various strategies employed within the construction of mise-en-scène, a significant portion of this, as I would like to argue, is transmitted through performance. The material detail of a performance – incorporating gesture, movement, voice, and even surrounding elements such as costume – as well as the way it its presented within a film is key to the establishment, invocation and coherence of genre. Furthermore, attention to the complexity of performance details, particularly in the manner in which they reverberate across texts, demonstrates the intricacy of genre and its inherent mutability. The Back to the Future trilogy represents a specific interest in the flexibility of genre. Within each film, and especially across all three, aspects of various genres are interlaced through both visual and narrative detail, thus constructing a dense layer of references both within and without the texts. To explore this patterning in more detail I will interrogate the contribution of performance to generic play through close analysis of Thomas F. Wilson’s performance of Biff/Griff/Burford Tannen and his central encounter with Marty McFly (Michael J. Fox) in each film. These moments take place in a fifties diner, a 1980s retro diner and a saloon respectively, each space contributing the similarities and differences in each repetition. Close attention to Wilson’s performance of each related character, which contains both modulations and repetitions used specifically to place each film’s central generic theme, demonstrates how embedded the play between genres and their flexibility is within the trilogy.

Amnesty international's language strategy put into practice: a case study of the translation of press releases

This paper investigates the language strategy and translation policies of Amnesty International by discussing the translation of a press release from a textual as well as an institutional point of view. Combining textual analysis with ethnographic methods of data collection and ideas from organisation studies, the paper aims to illustrate how the strategic use of language and translation play a vital role in mediating the NGO’s message and in contributing to its visibility and success. The findings of the textual analysis are contextualised within data collected at the local office of Amnesty International Vlaanderen to come to a better understanding of why particular translation strategies are being applied. The idea of an NGO spreading one consistent message is questioned by showing how different translation strategies apply to different languages and sections, thereby addressing the difficulty of defining translation in the context of news translation.

Transformation through translation: translation policies at Amnesty International

International non-governmental organisations (NGOs) are powerful political players who aim to influence global society. In order to be effective on a global scale, they must communicate their goals and achievements in different languages. Translation and translation policy play an essential role here. Despite NGOs’ important position in politics and society, not much is known about how these organisations, who often have limited funds available, organise their translation work. This study aims to contribute to Translation Studies, and more specifically to investigating institutional translation, by exploring translation policies at Amnesty International, one of the most successful and powerful human rights NGOs around the world. Translation policy is understood as comprising three components: translation management, translation practices, and translation beliefs, based on Spolsky’s study of language policy (2004). The thesis investigates how translation is organised and what kind of policies different Amnesty offices have in place, and how this is reflected in their translation products. The thesis thus also pursues how translation and translation policy impact on the organisation’s message and voice as it is spread around the world. An ethnographic approach is used for the analysis of various data sets that were collected during fieldwork. These include policy documents, guidelines on writing and translation, recorded interviews, e-mail correspondence, and fieldnotes. The thesis at first explores Amnesty’s global translation policy, and then presents the results of a comparative analysis of local translation policies at two concrete institutions: Amnesty International Language Resource Centre in Paris (AILRC-FR) and Amnesty International Vlaanderen (AIVL). A corpus of English source texts and Dutch (AIVL) and French (AILRC-FR) target texts are analysed. The findings of the analysis of translation policies and of the translation products are then combined to illustrate how translation impacts on Amnesty’s message and voice. The research results show that there are large differences in how translation is organised depending on the local office and the language(s), and that this also influences the way in which Amnesty’s message and voice are represented. For Dutch and French specifically, translation policies and translation products differ considerably. The thesis describes how these differences are often the result of different beliefs and assumptions relating to translation, and that staff members within Amnesty are not aware of the different conceptions of translation that exist within Amnesty International as a formal institution. Organising opportunities where translation can be discussed (meetings, workshops, online platforms) can help in reducing such differences. The thesis concludes by suggesting that an increased awareness of these issues will enable Amnesty to make more effective use of translation in its fight against human rights violations.

The politics of slowness and the traps of modernity

This chapter re-evaluates the diachronic, evolutionist model that establishes the Second World War as a watershed between classical and modern cinemas, and ‘modernity’ as the political project of ‘slow cinema’. I will start by historicising the connection between cinematic speed and modernity, going on to survey the veritable obsession with the modern that continues to beset film studies despite the vagueness and contradictions inherent in the term. I will then attempt to clarify what is really at stake within the modern-classical debate by analysing two canonical examples of Japanese cinema, drawn from the geidomono genre (films on the lives of theatre actors), Kenji Mizoguchi’s Story of the Late Chrysanthemums (Zangiku monogatari, 1939) and Yasujiro Ozu’s Floating Weeds (Ukigusa, 1954), with a view to investigating the role of the long take or, conversely, classical editing, in the production or otherwise of a supposed ‘slow modernity’. By resorting to Ozu and Mizoguchi, I hope to demonstrate that the best narrative films in the world have always combined a ‘classical’ quest for perfection with the ‘modern’ doubt of its existence, hence the futility of classifying cinema in general according to an evolutionary and Eurocentric model based on the classical-modern binary. Rather than on a confusing politics of the modern, I will draw on Bazin’s prophetic insight of ‘impure cinema’, a concept he forged in defence of literary and theatrical screen adaptations. Anticipating by more than half a century the media convergence on which the near totality of our audiovisual experience is currently based, ‘impure cinema’ will give me the opportunity to focus on the confluence of film and theatre in these Mizoguchi and Ozu films as the site of a productive crisis where established genres dissolve into self-reflexive stasis, ambiguity of expression and the revelation of the reality of the film medium, all of which, I argue, are more reliable indicators of a film’s political programme than historical teleology. At the end of the journey, some answers may emerge to whether the combination of the long take and the long shot are sufficient to account for a film’s ‘slowness’ and whether ‘slow’ is indeed the best concept to signify resistance to the destructive pace of capitalism.

Evaluating and optimizing oral formulations of live bacterial vaccines using a gastro-small intestine model

Gastrointestinal (GI) models that mimic physiological conditions in vitro are important tools for developing and optimizing biopharmaceutical formulations. Oral administration of live attenuated bacterial vaccines (LBV) can safely and effectively promote mucosal immunity but new formulations are required that provide controlled release of optimal numbers of viable bacterial cells, which must survive gastrointestinal transit overcoming various antimicrobial barriers. Here, we use a gastro-small intestine gut model of human GI conditions to study the survival and release kinetics of two oral LBV formulations: the licensed typhoid fever vaccine Vivotif comprising enteric coated capsules; and an experimental formulation of the model vaccine Salmonella Typhimurium SL3261 dried directly onto cast enteric polymer films and laminated to form a polymer film laminate (PFL). Neither formulation released significant numbers of viable cells when tested in the complete gastro-small intestine model. The poor performance in delivering viable cells could be attributed to a combination of acid and bile toxicity plus incomplete release of cells for Vivotif capsules, and to bile toxicity alone for PFL. To achieve effective protection from intestinal bile in addition to effective acid resistance, bile adsorbent resins were incorporated into the PFL to produce a new formulation, termed BR-PFL. Efficient and complete release of 4.4x107 live cells per dose was achieved from BR-PFL at distal intestinal pH, with release kinetics controlled by the composition of the enteric polymer film, and no loss in viability observed in any stage of the GI model. Use of this in vitro GI model thereby allowed rational design of an oral LBV formulation to maximize viable cell release.

Storage proteins and cell wall mobilisation in seeds of Sesbania virgata (Cav.) Pers. (Leguminosae)

The endosperm of seeds of Sesbania virgata (Cav.) Pers. accumulates galactomannan as a cell wall storage polysaccharide. It is hydrolysed by three enzymes, one of them being alpha-galactosidase. A great amount of protein bodies is found in the cytoplasm of endospermic cells, which are thought to play the major role as a nitrogen reserve in this seed. The present work aimed at understanding how the production of enzymes that degrade storage compounds is controlled. We performed experiments with addition of inhibitors of transcription (actinomycin-d and alpha-amanitin) and translation (cycloheximide) during and after germination. In order to follow the performance of storage mobilisation, we measured fresh mass, protein contents and alpha-galactosidase activity. All the inhibitors tested had little effect on seed germination and seedling development. Actinomycin-d and cycloheximide provoked a slight inhibition of the storage protein degradation and concomitantly lead to an elevation of the alpha-galactosidase activity. Although alpha-amanitin showed some effect on seedling development at latter stages, it presented the former effect and did not change galactomannan degradation performance. Our data suggest that some of the proteases may be synthesised de novo, whereas alpha-galactosidase seems to be present in the endosperm cells probably as an inactive polypeptide in the protein bodies, being probably activated by proteolysis when the latter organelle is disassembled. These evidences suggest the existence of a connection between storage proteins and carbohydrates mobilisation in seeds of S. virgata, which would play a role by assuring a balanced afflux of the carbon and nitrogen to the seedling development.

T3 rapidly modulates TSH beta mRNA stability and translational rate in the pituitary of hypothyroid rats

Whereas it is well known that T3 inhibits TSH beta gene transcription, its effects on TSH beta mRNA stability and translation have been poorly investigated. This study examined these possibilities, by evaluating the TSH beta transcripts poly(A) tail length, translational rate and binding to cytoskeleton, in pituitaries of thyroidectomized and sham-operated rats treated with T3 or saline, and killed 30 min thereafter. The hypothyroidism induced an increase of TSH beta transcript poly(A) tail, as well as of its content in ribosomes and attachment to cytoskeleton. The hypothyroid rats acutely treated with T3 exhibited a reduction of TSH beta mRNA poly(A) tail length and recruitment to ribosomes, indicating that this treatment decreased the stability and translation rate of TSH beta mRNA. Nevertheless, acute T3 administration to sham-operated rats provoked an increase of TSH beta transcripts binding to ribosomes. These data add new insight to an important role of T3 in rapidly regulating TSH gene expression at posttranscriptional level. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

MAGNETIC RESONANT X-RAY DIFFRACTION APPLIED TO THE STUDY OF EuTe FILMS AND MULTILAYERS

In this work we use magnetic resonant x-ray diffraction to study the magnetic properties of a 1.5 mu m EuTe film and an EuTe/PbTe superlattice (SL). The samples were grown by molecular beam epitaxy on (111) oriented BaF(2) substrates. The measurements were made at the Eu L(2) absorption edge, taking profit of the resonant enhancement of more than two orders in the magnetically diffracted intensity. At resonance, high counting rates above 11000 cps were obtained for the 1.5 gm EuTe film, allowing to check for the type II antiferromagnetic order of EuTe. An equal population of the three possible in-plane magnetic domains was found. The EuTe/PbTe SL magnetic peak showed a satellite structure, indicating the presence of magnetic correlations among the 5 ML (monolayers) EuTe layers across the 15 ML PbTe non-magnetic spacers. The temperature dependence of the integrated intensities of the film and the SL yielded different Neel temperatures T(N). The lower T(N) for the SL is explained considering the higher influence of the surface atoms, with partial bonds lost.