187 research outputs found
Potential limits of AAV-based gene therapy with the use of new transgenes expressing factor IX fusion proteins
Introduction: The variety of treatment for haemophilia B (HB) has recently improved with the emergence of both AAVâbased gene therapy and bioengineered human factor IX (hFIX) molecules with prolonged halfâlife due to fusion to either albumin (Alb) or immunoglobulin Fc fragment (Fc). /
Aim: Adenoâassociated viral vectors (AAV) mediating expression of hFIXâAlb and hFIXâFc fusion proteins was investigated for gene therapy of HB to explore if their extended halfâlife translates to higher plasma levels of FIX. /
Methods: Singleâstranded crossâpackaged AAV2/8 vectors expressing hFIXâAlb, hFIXâFc and hFIX were evaluated in vitro, and in mice. /
Results: Both hFIXâAlb and hFIXâFc fusion proteins were synthesized and expressed as single chains of expected size following AAVâmediated gene transfer in vitro and in vivo. The procoagulant properties of these hFIXâfusion proteins were comparable to wildâtype hFIX. However, their expression levels were threefold lower than wildâtype hFIX in vivo most likely due to inefficient secretion. /
Conclusion: This, the first, evaluation of hFIXâfusion proteins in the context of AAV gene transfer suggests that the hFIXâfusion proteins are secreted inefficiently from the liver, thus preventing their optimal use in gene therapy approaches
Servelle-Martorell syndrome with extensive upper limb involvement: a case report
This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens
User experiences with editorial control in online newspaper comment fields
This article investigates user experiences with editorial control in online newspaper comment fields following the public backlash against online comments after the 2011 terror attacks in Norway. We analyze data from a survey of online news consumers focusing on experiences and attitudes towards editorial control set against a spectrum between âinterventionistâ and ânoninterventionistâ positions. Results indicate that interventionist respondents rate the quality of online comments as poor, whereas noninterventionist respondents have most often experienced being the target of editorial control measures and feel that editorial control has intensified after the terror attacks. We conclude that newspapers should pay attention to the different needs of participants when devising strategies for editorial control. Media professionals should also consider changes to increase the transparency of moderation practices
Great Expectations: Voluntary Sports Clubs and Their Role in Delivering National Policy for English Sport
âThe original publication is available at www.springerlink.comâ. Copyright International Society for Third-Sector Research and The Johns Hopkins University. DOI: 10.1007/s11266-009-9095-yVoluntary sports clubs (VSCs) account for about a quarter of all volunteering in England. The volunteers work in a mutual aid, self-production, self-consumption system whose main purpose is identifying and nurturing high-level performers. But the new HMG/Sport England strategies leading to London 2012 expects volunteers to make a major contribution to sustaining and extending participation. The study utilized six focus group sessions with a total of 36 officials and members of 36 clubs across the six counties of Eastern England to assess whether and to what extent government policy objectives can be delivered through the voluntary sector. The study focused on the perceptions and attitudes of club members about being expected to serve public policy and the current pressures they and their clubs face. The results lead the authors to question the appropriateness, sensitivity, and feasibility of current sport policy, particularly the emphasis on VSCs as policy implementers.Peer reviewe
The Third sector in France and the Labour Market Policy
In France, like in other Western European countries, the third sector has been on a steady increase during the last decade as the results of the Johns Hopkins comparative project shows it. Today nonprofit organisations play also an increasing role in labour market policies. In a country with a corporatist welfare state, the access to the labour-market represents the key for social rights
Activism and radical politics in the digital age: Towards a typology
This article aims to develop a typology for evaluating different types of activism in the digital age, based on the ideal of radical democracy. Departing from this ideal, activism is approached in terms of processes of identification by establishing conflictual frontiers to outside Others as either adversaries or enemies. On the basis of these discussions, we outline a typology of four kinds of activists: the salon activist, the contentious activist, the law-abiding activist, and the Gandhian activist. The typologyâs first axis, between antagonism and agonism, is derived from normative discussions in radical democracy concerning developing frontiers. The second axis, about readiness to engage in civil disobedience, is derived from a review of studies of different forms of online activism. The article concludes by suggesting that the different forms of political engagement online have to be taken into account when studying how online activism can contribute to social change
Methods to Study Centrosomes and Cilia in Drosophila
The deposited item is a book chapter and is part of the series " Methods in Molecular Biology book series ([MIMB, volume 1454]) published by the publisher Humana Press.The deposited book chapter is a pre-print version and hasn't been submitted to peer reviewing.There is no public supplementary material available for this publication.This publication hasn't any creative commons license associated.Centrioles and cilia are highly conserved eukaryotic organelles. Drosophila melanogaster is a powerful genetic and cell biology model organism, extensively used to discover underlying mechanisms of centrosome and cilia biogenesis and function. Defects in centrosomes and cilia reduce fertility and affect different sensory functions, such as proprioception, olfaction, and hearing. The fly possesses a large diversity of ciliary structures and assembly modes, such as motile, immotile, and intraflagellar transport (IFT)-independent or IFT-dependent assembly. Moreover, all the diverse ciliated cells harbor centrioles at the base of the cilia, called basal bodies, making the fly an attractive model to better understand the biology of this organelle. This chapter describes protocols to visualize centrosomes and cilia by fluorescence and electron microscopy.Fundação Portuguesa para a CiĂȘncia e Tecnologia grants: (SFRH/BPD/87479/2012, SFRH/BD/52176/2013); EMBO installation grant; ERC starting grant.info:eu-repo/semantics/publishedVersio
âFriends call me racistâ: Experiences of repercussions from writing comments on newspaper websites
acceptedVersio
Interest Groups, NGOs or Civil Society Organisations? The Framing of Non-State Actors in the EU
Scholars have used varying terminology for describing non-state entities seeking to influence public policy or work with the EUâs institutions. This paper argues that the use of this terminology is not and should not be random, as different âframesâ come with different normative visions about the role(s) of these entities in EU democracy. A novel bibliometric analysis of 780 academic publications between 1992 and 2020 reveals that three frames stand out: The interest group frame, the NGO frame, as well as the civil society organisation frame; a number of publications also use multiple frames. This article reveals the specific democratic visions contained in these frames, including a pluralist view for interest groups; a governance view for NGOs as âthird sectorâ organisations, and participatory and deliberative democracy contributions for civil society organisations. The use of these frames has dynamically changed over time, with âinterest groupsâ on the rise. The results demonstrate the shifting focus of studies on non-state actors in the EU and consolidation within the sub-field; the original visions of European policy-makers emerging from the 2001 White Paper on governance may only partially come true
- âŠ