78 resultados para Seminal vesicle
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The technological constraints of early British television encouraged drama productions which emphasised the immediate, the enclosed and the close-up, an approach which Jason Jacobs described in the title of his seminal study as 'the intimate screen'. While Jacobs' book showed that this conception of early British television drama was only part of the reality, he did not focus on the role that special effects played in expanding the scope of the early television screen. This article will focus upon this role, showing that special effects were not only of use in expanding the temporal and spatial scope of television, but were also considered to be of interest to the audience as a way of exploring the new medium, receiving coverage in the popular press. These effects included pre-recorded film inserts, pre-recorded narration, multiple sets, model work and animation, combined with the live studio performances. Drawing upon archival research into television production files and scripts as well as audience responses and periodical coverage of television at the time of broadcast, this article will focus on telefantasy. This genre offered particular opportunities for utilising effects in ways that seemed appropriate for the experimentation with the form of television and for the drama narratives. This period also saw a variety of shifts within television as the BBC sought to determine a specific identity and understand the possibilities for the new medium.
This research also incorporates the BBC's own research and internal dialogue concerning audiences and how their tastes should best be met, at a time when the television audience was not only growing in terms of number but was also expanding geographically and socially beyond the moneyed Londoners who could afford the first television sets and were within range of the Alexandra Palace transmissions. The primary case study for this article will be the 1949 production of H.G.Wells’ The Time Machine, which incorporated pre-recorded audio and film inserts, which expanded the narrative out of the live studio performance both temporally and spatially, with the effects work receiving coverage in the popular magazine Illustrated. Other productions considered will be the 1938 and 1948 productions of RUR, the 1948 production of Blithe Spirit, and the 1950 adaptation of The Strange Case of Dr Jekyll and Mr Hyde. Despite the focus on telefantasy, this article will also include examples from other genres, both dramatic and factual, showing how the BBC's response to the changing television audience was to restrict drama to a more 'realistic' aesthetic and to move experimentation with televisual form to non-drama productions such as variety performances.
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his essay is premised on the following: a conspiracy to fix or otherwise manipulate the outcome of a sporting event for profitable purpose. That conspiracy is in turn predicated on the conspirators’ capacity to: (a) ensure that the fix takes place as pre-determined; (b) manipulate the betting markets that surround the sporting event in question; and (c) collect their winnings undetected by either the betting industry’s security systems or the attention of any national regulatory body or law enforcement agency.
Unlike many essays on this topic, this contribution does not focus on the “fix”– part (a) of the above equation. It does not seek to explain how or why a participant or sports official might facilitate a betting scam through either on-field behaviour that manipulates the outcome of a game or by presenting others with privileged inside information in advance of a game. Neither does this contribution seek to give any real insight into the second part of the above equation: how such conspirators manipulate a sports betting market by playing or laying the handicap or in-play or other offered betting odds. In fact, this contribution is not really about the mechanics of sports betting or match fixing at all; rather it is about the sometimes under explained reason why match fixing has reportedly become increasingly attractive as of late to international crime syndicates. That reason relates to the fact that given the traditional liquidity of gambling markets, sports betting can, and has long been, an attractively accessible conduit for criminal syndicates to launder the proceeds of crime. Accordingly, the term “winnings”, noted in part (c) of the above equation, takes on an altogether more nefarious meaning.
This essay’s attempt to review the possible links between match fixing in sport, gambling-related “winnings” and money laundering is presented in four parts.
First, some context will be given to what is meant by money laundering, how it is currently policed internationally and, most importantly, how the growth of online gambling presents a unique set of vulnerabilities and opportunities to launder the proceeds of crime. The globalisation of organised crime, sports betting and transnational financial services now means that money laundering opportunities have moved well beyond a flutter on the horses at your local racetrack or at the roulette table of your nearest casino. The growth of online gambling platforms means that at a click it is possible for the proceeds of crime in one jurisdiction to be placed on a betting market in another jurisdiction with the winnings drawn down and laundered in a third jurisdiction and thus the internationalisation of gambling-related money laundering threatens the integrity of sport globally.
Second, and referring back to the infamous hearings of the US Senate Special Committee to Investigate Organised Crime in Interstate Commerce of the early 1950s, (“the Kefauver Committee”), this article will begin by illustrating the long standing interest of organised crime gangs – in this instance, various Mafia families in the United States – in money laundering via sports gambling-related means.
Third, and using the seminal 2009 report “Money Laundering through the Football Sector” by the Financial Action Task Force (FATF, an inter-governmental body established in 1989 to promote effective implementation of legal, regulatory and operational measures for combating money laundering, terrorist financing and other related threats to the integrity of the international financial system), this essay seeks to assess the vulnerabilities of international sport to match fixing, as motivated in part by the associated secondary criminality of tax evasion and transnational economic crime.
The fourth and concluding parts of the essay spin from problems to possible solutions. The underlying premise here is that heretofore there has been an insularity to the way that sports organisations have both conceptualised and sought to address the match fixing threat e.g., if we (in sport) initiate player education programmes; establish integrity units; enforce codes of conduct and sanctions strictly; then our integrity or brand should be protected. This essay argues that, although these initiatives are important, the source and process of match fixing is beyond sport’s current capacity, as are the possible solutions.
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BACKGROUND: Clathrin is a multimeric protein involved in vesicle coat assembly. Recently clathrin distribution was reported to change during the cell cycle and was found to associate with the mitotic spindle. Here we test whether the recruitment of clathrin to the spindle is indicative of a critical functional contribution to mitosis.
METHODOLOGY/PRINCIPAL FINDINGS: Previously a chicken pre-B lymphoma cell line (DKO-R) was developed in which the endogenous clathrin heavy chain alleles were replaced with the human clathrin heavy chain under the control of a tetracycline-regulatable promoter. Receptor-mediated and fluid-phase endocytosis were significantly inhibited in this line following clathrin knockout, and we used this to explore the significance of clathrin heavy chain expression for cell cycle progression. We confirmed using confocal microscopy that clathrin colocalised with tubulin at mitotic spindles. Using a propidium iodide flow cytometric assay we found no statistical difference in the cell cycle distribution of the knockout cells versus the wild-type. Additionally, we showed that the ploidy and the recovery kinetics following cell cycle arrest with nocodazole were unchanged by repressing clathrin heavy chain expression.
CONCLUSIONS/SIGNIFICANCE: We conclude that the association of clathrin with the mitotic spindle and the contribution of clathrin to endocytosis are evolutionarily conserved. However we find that the contribution of clathrin to mitosis is less robust and dependent on cellular context. In other cell-lines silencing RNA has been used by others to knockdown clathrin expression resulting in an increase in the mitotic index of the cells. We show an effect on the G2/M phase population of clathrin knockdown in HEK293 cells but show that repressing clathrin expression in the DKO-R cell-line has no effect on the size of this population. Consequently this work highlights the need for a more detailed molecular understanding of the recruitment and function of clathrin at the spindle, since the localisation but not the impact of clathrin on mitosis appears to be robust in plants, mammalian and chicken B-cells.
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Internalization of cargo proteins and lipids at the cell surface occurs in both a constitutive and signal-regulated manner through clathrin-mediated and other endocytic pathways. Clathrin-coated vesicle formation is a principal uptake route in response to signalling events. Protein-lipid and protein-protein interactions control both the targeting of signalling molecules and their binding partners to membrane compartments and the assembly of clathrin coats. An emerging aspect of membrane trafficking research is now addressing how signalling cascades and vesicle coat assembly and subsequently disassembly are integrated.
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Dynamin is a large GTPase with a relative molecular mass of 96,000 (Mr 96K) that is involved in clathrin-mediated endocytosis and other vesicular trafficking processes. Although its function is apparently essential for scission of newly formed vesicles from the plasma membrane, the nature of dynamin's role in the scission process is still unclear. It has been proposed that dynamin is a regulator (similar to classical G proteins) of downstream effectors. Here we report the analysis of several point mutants of dynamin's GTPase effector (GED) and GTPase domains. We show that oligomerization and GTP binding alone, by dynamin, are not sufficient for endocytosis in vivo. Rather, efficient GTP hydrolysis and an associated conformational change are also required. These data argue that dynamin has a mechanochemical function in vesicle scission.
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Rab5-dependent endosome fusion is sensitive to the phosphoinositide 3-kinase inhibitor, wortmannin. It has been proposed that phosphoinositide 3-kinase activity may be required for activation of rab5 by influencing its nucleotide cycle such as to promote its active GTP state. In this report we demonstrate that endosome fusion remains sensitive to wortmannin despite preloading of endosomes with stimulatory levels of a GTPase-defective mutant rab5(Q79L) or of a xanthosine triphosphate-binding mutant, rab5(D136N), in the presence of the nonhydrolysable analogue XTPgammaS. These results suggest that activation of rab5 cannot be the principal function of the wortmannin-sensitive factor on the endosome fusion pathway. This result is extrapolated to all GTPases by demonstrating that endosome fusion remains wortmannin sensitive despite prior incubation with the nonhydrolysable nucleotide analogue GTPgammaS. Consistent with these results, direct measurement of clathrin-coated vesicle-stimulated nucleotide dissociation from exogenous rab5 was insensitive to the presence of wortmannin. A large excess of rab5(Q79L), beyond levels required for maximal stimulation of the fusion assay, afforded protection against wortmannin inhibition, and partial protection was also observed with an excess of wild-type rab5 independent of GTPgammaS.
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As all human beings are consumers of health care provision across the life span and in receipt of care delivered by accountable health care professionals, all should have the right to be involved in shaping the future of their own health care. Rights-based participation, when applied successfully, has the potential to inform and influence the delivery of child health care, the child’s experience of health care, plus children’s nursing education (Coyne & Gallagher, 2011). The “right” of every child and young person to participate in research that relates to their own health care is also sustained by the author’s lead position as a Senior Lecturer in Higher Education for pre-registration children’s nursing in Northern Ireland and the appreciation of their voice when practicing as a registered children’s nurse and ward sister. The report provides an insight into seminal work on human and child rights; the historical context of children in Western society, and the evolution of children’s nursing amid the child’s right to participate in shaping their own health care.
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Shallow hydrophobic insertions and crescent-shaped BAR scaffolds promote membrane curvature. Here, we investigate membrane fission by shallow hydrophobic insertions quantitatively and mechanistically. We provide evidence that membrane insertion of the ENTH domain of epsin leads to liposome vesiculation, and that epsin is required for clathrin-coated vesicle budding in cells. We also show that BAR-domain scaffolds from endophilin, amphiphysin, GRAF, and β2-centaurin limit membrane fission driven by hydrophobic insertions. A quantitative assay for vesiculation reveals an antagonistic relationship between amphipathic helices and scaffolds of N-BAR domains in fission. The extent of vesiculation by these proteins and vesicle size depend on the number and length of amphipathic helices per BAR domain, in accord with theoretical considerations. This fission mechanism gives a new framework for understanding membrane scission in the absence of mechanoenzymes such as dynamin and suggests how Arf and Sar proteins work in vesicle scission.
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Clathrin-mediated endocytosis, the major pathway for ligand internalization into eukaryotic cells, is thought to be initiated by the clustering of clathrin and adaptors around receptors destined for internalization. However, here we report that the membrane-sculpting F-BAR domain-containing Fer/Cip4 homology domain-only proteins 1 and 2 (FCHo1/2) were required for plasma membrane clathrin-coated vesicle (CCV) budding and marked sites of CCV formation. Changes in FCHo1/2 expression levels correlated directly with numbers of CCV budding events, ligand endocytosis, and synaptic vesicle marker recycling. FCHo1/2 proteins bound specifically to the plasma membrane and recruited the scaffold proteins eps15 and intersectin, which in turn engaged the adaptor complex AP2. The FCHo F-BAR membrane-bending activity was required, leading to the proposal that FCHo1/2 sculpt the initial bud site and recruit the clathrin machinery for CCV formation.
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Intersectin is a multidomain dynamin-binding protein implicated in numerous functions in the nervous system, including synapse formation and endocytosis. Here, we demonstrate that during neurotransmitter release in the central synapse, intersectin, like its binding partner dynamin, is redistributed from the synaptic vesicle pool to the periactive zone. Acute perturbation of the intersectin-dynamin interaction by microinjection of either intersectin antibodies or Src homology 3 (SH3) domains inhibited endocytosis at the fission step. Although the morphological effects induced by the different reagents were similar, antibody injections resulted in a dramatic increase in dynamin immunoreactivity around coated pits and at constricted necks, whereas synapses microinjected with the GST (glutathione S-transferase)-SH3C domain displayed reduced amounts of dynamin in the neck region. Our data suggest that intersectin controls the amount of dynamin released from the synaptic vesicle cluster to the periactive zone and that it may regulate fission of clathrin-coated intermediates.
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Efficient synaptic vesicle membrane recycling is one of the key factors required to sustain neurotransmission. We investigated potential differences in the compensatory endocytic machineries in two glutamatergic synapses with phasic and tonic patterns of activity in the lamprey spinal cord. Post-embedding immunocytochemistry demonstrated that proteins involved in synaptic vesicle recycling, including dynamin, intersectin, and synapsin, occur at higher levels (labeling per vesicle) in tonic dorsal column synapses than in phasic reticulospinal synapses. Synaptic vesicle protein 2 occurred at similar levels in the two types of synapse. After challenging the synapses with high potassium stimulation for 30 min the vesicle pool in the tonic synapse was maintained at a normal level, while that in the phasic synapse was partly depleted along with expansion of the plasma membrane and accumulation of clathrin-coated intermediates at the periactive zone. Thus, our results indicate that an increased efficiency of the endocytic machinery in a synapse may be one of the factors underlying the ability to sustain neurotransmission at high rates.
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During the past decade, many molecular components of clathrin-mediated endocytosis have been identified and proposed to play various hypothetical roles in the process [Nat. Rev. Neurosci. 1 (2000) 161; Nature 422 (2003) 37]. One limitation to the evaluation of these hypotheses is the efficiency and resolution of immunolocalization protocols currently in use. In order to facilitate the evaluation of these hypotheses and to understand more fully the molecular mechanisms of clathrin-mediated endocytosis, we have developed a protocol allowing enhanced and reliable subcellular immunolocalization of proteins in synaptic endocytic zones in situ. Synapses established by giant reticulospinal axons in lamprey are used as a model system for these experiments. These axons are unbranched and reach up to 80-100 microm in diameter. Synaptic active zones and surrounding endocytic zones are established on the surface of the axonal cylinder. To provide access for antibodies to the sites of synaptic vesicle recycling, axons are lightly fixed and cut along their longitudinal axis. To preserve the ultrastructure of the synaptic endocytic zone, antibodies are applied without the addition of detergents. Opened axons are incubated with primary antibodies, which are detected with secondary antibodies conjugated to gold particles. Specimens are then post-fixed and processed for electron microscopy. This approach allows preservation of the ultrastructure of the endocytic sites during immunolabeling procedures, while simultaneously achieving reliable immunogold detection of proteins on endocytic intermediates. To explore the utility of this approach, we have investigated the localization of a GTPase, dynamin, on clathrin-coated intermediates in the endocytic zone of the lamprey giant synapse. Using the present immunogold protocol, we confirm the presence of dynamin on late stage coated pits [Nature 422 (2003) 37] and also demonstrate that dynamin is recruited to the coat of endocytic intermediates from the very early stages of the clathrin coat formation. Thus, our experiments show that the current pre-embedding immunogold method is a useful experimental tool to study the molecular mechanisms of synaptic vesicle recycling.
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Extracellular vesicles (EVs) released by parasites have important roles in establishing and maintaining infection. Analysis of the soluble and vesicular secretions of adult Fasciola hepatica has established a definitive characterisation of the total secretome of this zoonotic parasite. Fasciola secretes at least two sub-populations of EVs that differ according to size, cargo molecules and site of release from the parasite. The larger EVs are released from the specialised cells that line the parasite gastrodermus and contain the zymogen of the 37 kDa cathepsin L peptidase that performs a digestive function. The smaller exosome-like vesicle population originate from multivesicular bodies within the tegumental syncytium and carry many previously described immunomodulatory molecules that could be delivered into host cells. By integrating our proteomics data with recently available transcriptomic datasets we have detailed the pathways involved with EV biogenesis in F. hepatica and propose that the small exosome biogenesis occurs via ESCRT-dependent MVB formation in the tegumental syncytium before being shed from the apical plasma membrane. Furthermore, we found that the molecular machinery required for EV biogenesis is constitutively expressed across the intra-mammalian development stages of the parasite. By contrast, the cargo molecules packaged within the EVs are developmentally regulated, most likely to facilitate the parasites migration through host tissue and to counteract host immune attack.
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The Easter Rising of 1916 not only destroyed much of the centre of Dublin - it changed the course of Irish history. But why did it happen? What was the role of ordinary people in this extraordinary event? What motivated them and what were their aims? These basic questions continue to divide historians of modern Ireland.
The Rising is the story of Easter 1916 from the perspective of those who made it, focusing on the experiences of rank and file revolutionaries. Fearghal McGarry makes use of a unique source that has only recently seen the light of day - a collection of over 1,700 eye-witness statements detailing the political activities of members of Sinn Féin and militant groups such as the Irish Republican Brotherhood. This collection represents one of the richest and most comprehensive oral history archives devoted to any modern revolution, providing new insights on almost every aspect of this seminal period.
The Rising shows how people from ordinary backgrounds became politicized and involved in the struggle for Irish independence. McGarry illuminates their motives, concerns, and aspirations, highlighting the importance of the Great War as a catalyst for the uprising. He concludes by exploring the Rising's revolutionary aftermath, which in time saw the creation of the independent state we see today.
Published to mark the centenary of the Easter Rising, this edition includes a new preface which reflects on the continuing importance of the Easter Rising as a symbol of Irish nationhood and which looks at the centenary commemorations in both Ireland and the UK within the wider context of the 'Decade of Centenaries.'
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This paper explores the theme of exhibiting architectural research through a particular example, the development of the Irish pavilion for the 14th architectural biennale, Venice 2014. Responding to Rem Koolhaas’s call to investigate the international absorption of modernity, the Irish pavilion became a research project that engaged with the development of the architectures of infrastructure in Ireland in the twentieth and twenty-first centuries. Central to this proposition was that infrastructure is simultaneously a technological and cultural construct, one that for Ireland occupied a critical position in the building of a new, independent post-colonial nation state, after 1921.
Presupposing infrastructure as consisting of both visible and invisible networks, the idea of a matrix become a central conceptual and visual tool in the curatorial and design process for the exhibition and pavilion. To begin with this was a two-dimensional grid used to identify and order what became described as a series of ten ‘infrastructural episodes’. These were determined chronologically across the decades between 1914 and 2014 and their spatial manifestations articulated in terms of scale: micro, meso and macro. At this point ten academics were approached as researchers. Their purpose was twofold, to establish the broader narratives around which the infrastructures developed and to scrutinise relevant archives for compelling visual material. Defining the meso scale as that of the building, the media unearthed was further filtered and edited according to a range of categories – filmic/image, territory, building detail, and model – which sought to communicate the relationship between the pieces of architecture and the larger systems to which they connect. New drawings realised by the design team further iterated these relationships, filling in gaps in the narrative by providing composite, strategic or detailed drawings.
Conceived as an open-ended and extendable matrix, the pavilion was influenced by a series of academic writings, curatorial practices, artworks and other installations including: Frederick Kiesler’s City of Space (1925), Eduardo Persico and Marcello Nizzoli’s Medaglio d’Oro room (1934), Sol Le Witt’s Incomplete Open Cubes (1974) and Rosalind Krauss’s seminal text ‘Grids’ (1979). A modular frame whose structural bays would each hold and present an ‘episode’, the pavilion became both a visual analogue of the unseen networks embodying infrastructural systems and a reflection on the predominance of framed structures within the buildings exhibited. Sharing the aspiration of adaptability of many of these schemes, its white-painted timber components are connected by easily-dismantled steel fixings. These and its modularity allow the structure to be both taken down and re-erected subsequently in different iterations. The pavilion itself is, therefore, imagined as essentially provisional and – as with infrastructure – as having no fixed form. Presenting archives and other material over time, the transparent nature of the space allowed these to overlap visually conveying the nested nature of infrastructural production. Pursuing a means to evoke the qualities of infrastructural space while conveying a historical narrative, the exhibition’s termination in the present is designed to provoke in the visitor, a perceptual extension of the matrix to engage with the future.