592 research outputs found

    Entry pathways of herpes simplex virus type 1 into human keratinocytes are dynamin- and cholesterol-dependent

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    Herpes simplex virus type 1 (HSV-1) can enter cells via endocytic pathways or direct fusion at the plasma membrane depending on the cell line and receptor(s). Most studies into virus entry have used cultured fibroblasts but since keratinocytes represent the primary entry site for HSV-1 infection in its human host, we initiated studies to characterize the entry pathway of HSV-1 into human keratinocytes. Electron microscopy studies visualized free capsids in the cytoplasm and enveloped virus particles in vesicles suggesting viral uptake both by direct fusion at the plasma membrane and by endocytic vesicles. The ratio of the two entry modes differed in primary human keratinocytes and in the keratinocyte cell line HaCaT. Inhibitor studies further support a role for endocytosis during HSV-1 entry. Infection was inhibited by the cholesterol-sequestering drug methyl-beta-cyclodextrin, which demonstrates the requirement for host cholesterol during virus entry. Since the dynamin-specific inhibitor dynasore and overexpression of a dominant-negative dynamin mutant blocked infection, we conclude that the entry pathways into keratinocytes are dynamin-mediated. Electron microscopy studies confirmed that virus uptake is completely blocked when the GTPase activity of dynamin is inhibited. Ex vivo infection of murine epidermis that was treated with dynasore further supports the essential role of dynamin during entry into the epithelium. Thus, we conclude that HSV-1 can enter human keratinocytes by alternative entry pathways that require dynamin and host cholesterol

    'Surely the most natural scenario in the worldā€™: Representations of ā€˜Familyā€™ in BBC Pre-school Television

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    Historically, the majority of work on British childrenā€™s television has adopted either an institutional or an audience focus, with the texts themselves often overlooked. This neglect has meant that questions of representation in British childrenā€™s television ā€“ including issues such as family, gender, class or ethnicity - have been infrequently analysed in the UK context. In this article, we adopt a primarily qualitative methodology and analyse the various textual manifestations of ā€˜familyā€™, group, or community as represented in a selected number of BBC pre-school programmes. In doing so, we question the (limited amount of) international work that has examined representations of the family in childrenā€™s television, and argue that nuclear family structures do not predominate in this sphere

    Doing it for the kids?: The discursive construction of the teenager and teenage sexuality in E4ā€™s Skins

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    The teen series is often regarded by television scholars as an inherently American genre. Indeed, the genre is marked by US constructs, such as the cheerleader, jock, homecoming dance and prom and, in turn, teen television scholarship has focused almost exclusively on US texts. However, more recent years have seen the emergence of British teen drama series, most notably Skins (E4, 2007-), which has been so successful that it has spawned an (albeit short-lived) US version which aired on MTV. In an attempt to redress the dearth of academic study of British teen dramas, this article explores Skins in more detail. Journalistic discourse on the programme has frequently emphasised the series' nihilism in contrast to the didacticism that characterises its US generic counterparts, which the series' creators justify by claims for its authenticity. This article moves beyond the authentic/inauthentic debate to explore instead the discursive construction of the teenager and teenage sexuality in the specific context of broadcasting in the UK. Thus, after situating Skins in relation to the history of youth programming in Britain and, specifically, on Channel 4, the article will explore issue-led storylines involving teenage sexuality in more detail. It will argue that despite the programme's nihilistic ethos, Skins is underpinned by more conservative ideologies, particularly regarding the depiction of gender and sexuality. In turn, this ambivalence makes it difficult to discern the programme's ideological stance on sexual issues

    New generalized fuzzy metrics and fixed point theorem in fuzzy metric space

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    In this paper, in fuzzy metric spaces (in the sense of Kramosil and Michalek (Kibernetika 11:336-344, 1957)) we introduce the concept of a generalized fuzzy metric which is the extension of a fuzzy metric. First, inspired by the ideas of Grabiec (Fuzzy Sets Syst. 125:385-389, 1989), we define a new G-contraction of Banach type with respect to this generalized fuzzy metric, which is a generalization of the contraction of Banach type (introduced by M Grabiec). Next, inspired by the ideas of Gregori and Sapena (Fuzzy Sets Syst. 125:245-252, 2002), we define a new GV-contraction of Banach type with respect to this generalized fuzzy metric, which is a generalization of the contraction of Banach type (introduced by V Gregori and A Sapena). Moreover, we provide the condition guaranteeing the existence of a fixed point for these single-valued contractions. Next, we show that the generalized pseudodistance J:XƗXā†’[0,āˆž) (introduced by Włodarczyk and Plebaniak (Appl. Math. Lett. 24:325-328, 2011)) may generate some generalized fuzzy metric NJ on X. The paper includes also the comparison of our results with those existing in the literature

    Intelligence within BAOR and NATO's Northern Army Group

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    During the Cold War the UK's principal military role was its commitment to the North Atlantic Treaty Organisation (NATO) through the British Army of the Rhine (BAOR), together with wartime command of NATO's Northern Army Group. The possibility of a surprise attack by the numerically superior Warsaw Pact forces ensured that great importance was attached to intelligence, warning and rapid mobilisation. As yet we know very little about the intelligence dimension of BAOR and its interface with NATO allies. This article attempts to address these neglected issues, ending with the impact of the 1973 Yom Kippur War upon NATO thinking about warning and surprise in the mid-1970s. It concludes that the arrangements made by Whitehall for support to BAOR from national assets during crisis or transition to war were - at best - improbable. Accordingly, over the years, BAOR developed its own unique assets in the realm of both intelligence collection and special operations in order to prepare for the possible outbreak of conflict

    Mediating the Presence of Others: Reconceptualising Co-Presence as Mediated Intimacy

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    Drawing insight from queer and media studies, this article analyses data from the UK study Adultsā€™ Media Lives. The authors claim that this study reveals the significance of peopleā€™s intimate relationships to their media practices, highlighting in particular how peopleā€™s media practices mediate the ā€˜presenceā€™ of others. The authors put forward the concept of mediated intimacy to capture both the cultural intimacy people have with media and the mediation of intimacy by media practices. Mediating intimacy has implications for normative conceptions of intimate life, including the significance of ā€˜timeā€™ to the values of ā€˜homeā€™ and ā€˜workā€™
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