912 research outputs found

    Film support and the challenge of ‘sustainability’: on wing design, wax and feathers, and bolts from the blue

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    In recognition of the importance of film in generating both economic and cultural value, the UK Labour government set up a new agency – the United Kingdom Film Council (UKFC) – in 2000 with a remit to build a sustainable film industry. But, reflecting a plethora of differing expectations in relation to the purposes behind public support for film, the UKFC's agenda shifted and broadened over the organisation's lifetime (2000–11). Apparently unconvinced by the UKFC's achievements, the Coalition government which came to power in May 2010 announced the Council's abolition and reassigned its responsibilities as part of a general cost-cutting strategy. Based on original empirical research, this article examines how the UKFC's sense of strategic direction was determined, how and why the balance of objectives it pursued changed over time and what these shifts tell us about the nature of film policy and the challenges facing bodies that are charged with enacting it in the twenty-first century

    Bacterial rotary export ATPases are allosterically regulated by the nucleotide second messenger cyclic-di-GMP

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    The widespread second messenger molecule cyclic di-GMP (cdG) regulates the transition from motile and virulent lifestyles to sessile, biofilm-forming ones in a wide range of bacteria. Many pathogenic and commensal bacterial-host interactions are known to be controlled by cdG signaling. Although the biochemistry of cyclic dinucleotide metabolism is well understood, much remains to be discovered about the downstream signaling pathways that induce bacterial responses upon cdG binding. As part of our ongoing research into the role of cdG signaling in plant-associated Pseudomonas species, we carried out an affinity capture screen for cdG binding proteins in the model organism Pseudomonas fluorescens SBW25. The flagella export AAA+ ATPase FliI was identified as a result of this screen and subsequently shown to bind specifically to the cdG molecule, with a KD in the low micromolar range. The interaction between FliI and cdG appears to be very widespread. In addition to FliI homologs from diverse bacterial species, high affinity binding was also observed for the type III secretion system homolog HrcN and the type VI ATPase ClpB2. The addition of cdG was shown to inhibit FliI and HrcN ATPase activity in vitro. Finally, a combination of site-specific mutagenesis, mass spectrometry, and in silico analysis was used to predict that cdG binds to FliI in a pocket of highly conserved residues at the interface between two FliI subunits. Our results suggest a novel, fundamental role for cdG in controlling the function of multiple important bacterial export pathways, through direct allosteric control of export ATPase proteins

    Twirling and Whirling: Viscous Dynamics of Rotating Elastica

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    Motivated by diverse phenomena in cellular biophysics, including bacterial flagellar motion and DNA transcription and replication, we study the overdamped nonlinear dynamics of a rotationally forced filament with twist and bend elasticity. Competition between twist injection, twist diffusion, and writhing instabilities is described by a novel pair of coupled PDEs for twist and bend evolution. Analytical and numerical methods elucidate the twist/bend coupling and reveal two dynamical regimes separated by a Hopf bifurcation: (i) diffusion-dominated axial rotation, or twirling, and (ii) steady-state crankshafting motion, or whirling. The consequences of these phenomena for self-propulsion are investigated, and experimental tests proposed.Comment: To be published in Physical Review Letter

    A Minimal Model of Metabolism Based Chemotaxis

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    Since the pioneering work by Julius Adler in the 1960's, bacterial chemotaxis has been predominantly studied as metabolism-independent. All available simulation models of bacterial chemotaxis endorse this assumption. Recent studies have shown, however, that many metabolism-dependent chemotactic patterns occur in bacteria. We hereby present the simplest artificial protocell model capable of performing metabolism-based chemotaxis. The model serves as a proof of concept to show how even the simplest metabolism can sustain chemotactic patterns of varying sophistication. It also reproduces a set of phenomena that have recently attracted attention on bacterial chemotaxis and provides insights about alternative mechanisms that could instantiate them. We conclude that relaxing the metabolism-independent assumption provides important theoretical advances, forces us to rethink some established pre-conceptions and may help us better understand unexplored and poorly understood aspects of bacterial chemotaxis

    An intervention to reassure patients about test results in rapid access chest pain clinic: a pilot randomised controlled trial

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    BACKGROUND: Most people referred to rapid access chest pain clinics have non-cardiac chest pain, and in those diagnosed with stable coronary heart disease, guidance recommends that first-line treatment is usually medication rather than revascularisation. Consequently, many patients are not reassured they have the correct diagnosis or treatment. A previous trial reported that, in people with non-cardiac chest pain, a brief discussion with a health psychologist before the tests about the meaning of potential results led to people being significantly more reassured. The aim of this pilot was to test study procedures and inform sample size for a future multi-centre trial and to gain initial estimates of effectiveness of the discussion intervention. METHODS: This was a two-arm pilot randomised controlled trial in outpatient rapid access chest pain clinic in 120 people undergoing investigation for new onset, non-urgent chest pain. Eligible participants were randomised to receive either: a discussion about the meaning and implication of test results, delivered by a nurse before tests in clinic, plus a pre-test pamphlet covering the same information (Discussion arm) or the pre-test pamphlet alone (Pamphlet arm). Main outcome measures were recruitment rate and feasibility for a future multi-centre trial, with an estimate of reassurance in the groups at month 1 and 6 using a 5-item patient-reported scale. RESULTS: Two hundred and seventy people attended rapid access chest pain clinic during recruitment and 120/270 participants (44%) were randomised, 60 to each arm. There was no evidence of a difference between the Discussion and Pamphlet arms in the mean reassurance score at month 1 (34.2 vs 33.7) or at month 6 (35.3 vs 35.9). Patient-reported chest pain and use of heart medications were also similar between the two arms. CONCLUSIONS: A larger trial of the discussion intervention in the UK would not be warranted. Patients reported high levels of reassurance which were similar in patients receiving the discussion with a nurse and in those receiving a pamphlet alone. TRIAL REGISTRATION: Current Controlled Trials ISRCTN60618114 (assigned 27.05.2011). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2261-14-138) contains supplementary material, which is available to authorized users
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