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Subject: article × Publisher: Amsterdam [u.a.] : Elsevier ×

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    Complement activation by carbon nanotubes and its influence on the phagocytosis and cytokine response by macrophages
    (Amsterdam [u.a.] : Elsevier, 2014) Pondman, K.M.; Sobik, M.; Nayak, A.; Tsolaki, A.G.; Jäkel, A.; Flahaut, E.; Hampel, S.; ten Haken, B.; Sim, R.B.; Kishore, U.
    Carbon nanotubes (CNTs) have promised a range of applications in biomedicine. Although influenced by the dispersants used, CNTs are recognized by the innate immune system, predominantly by the classical pathway of the complement system. Here, we confirm that complement activation by the CNT used continues up to C3 and C5, indicating that the entire complement system is activated including the formation of membrane-attack complexes. Using recombinant forms of the globular regions of human C1q (gC1q) as inhibitors of CNT-mediated classical pathway activation, we show that C1q, the first recognition subcomponent of the classical pathway, binds CNTs via the gC1q domain. Complement opsonisation of CNTs significantly enhances their uptake by U937 cells, with concomitant downregulation of pro-inflammatory cytokines and up-regulation of anti-inflammatory cytokines in both U937 cells and human monocytes. We propose that CNT-mediated complement activation may cause recruitment of cellular infiltration, followed by phagocytosis without inducing a pro-inflammatory immune response. From the Clinical Editor: This study highlights the importance of the complement system in response to carbon nanontube administration, suggesting that the ensuing complement activation may cause recruitment of cellular infiltration, followed by phagocytosis without inducing a pro-inflammatory immune response.
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    Opening up knowledge systems for better responses to global environmental change
    (Amsterdam [u.a.] : Elsevier, 2013) Cornell, S.; Berkhout, F.; Tuinstra, W.; Tàbara, J.D.; Jäger, J.; Chabay, I.; de Wit, B.; Langlais, R.; Mills, D.; Moll, P.; Otto, I.M.; Petersen, A.; Pohl, C.; van Kerkhoff, L.
    Linking knowledge with action for effective societal responses to persistent problems of unsustainability requires transformed, more open knowledge systems. Drawing on a broad range of academic and practitioner experience, we outline a vision for the coordination and organization of knowledge systems that are better suited to the complex challenges of sustainability than the ones currently in place. This transformation includes inter alia: societal agenda setting, collective problem framing, a plurality of perspectives, integrative research processes, new norms for handling dissent and controversy, better treatment of uncertainty and of diversity of values, extended peer review, broader and more transparent metrics for evaluation, effective dialog processes, and stakeholder participation. We set out institutional and individual roadmaps for achieving this vision, calling for well-designed, properly resourced, longitudinal, international learning programs.