39 research outputs found

    Helix movement is coupled to displacement of the second extracellular loop in rhodopsin activation

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    The second extracellular loop (EL2) of rhodopsin forms a cap over the binding site of its photoreactive 11-cis retinylidene chromophore. A crucial question has been whether EL2 forms a reversible gate that opens upon activation or acts as a rigid barrier. Distance measurements using solid-state 13C NMR spectroscopy between the retinal chromophore and the β4 strand of EL2 show that the loop is displaced from the retinal binding site upon activation, and there is a rearrangement in the hydrogen-bonding networks connecting EL2 with the extracellular ends of transmembrane helices H4, H5 and H6. NMR measurements further reveal that structural changes in EL2 are coupled to the motion of helix H5 and breaking of the ionic lock that regulates activation. These results provide a comprehensive view of how retinal isomerization triggers helix motion and activation in this prototypical G protein-coupled receptor. © 2009 Nature America, Inc. All rights reserved

    Government Influence on Patient Organizations

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    Patient organizations increasingly play an important role in health care decision-making in Western countries. The Netherlands is one of the countries where this trend has gone furthest. In the literature some problems are identified, such as instrumental use of patient organizations by care providers, health insurers and the pharmaceutical industry. To strengthen the position of patient organizations government funding is often recommended as a solution. In this paper we analyze the ties between Dutch government and Dutch patient organizations to learn more about the effects of such a relationship between government and this part of civil society. Our study is based on official government documents and existing empirical research on patient organizations. We found that government influence on patient organizations has become quite substantial with government influencing the organizational structure of patient organizations, the activities these organizations perform and even their ideology. Financing patient organizations offers the government an important means to hold them accountable. Although the ties between patient organizations and the government enable the former to play a role that can be valued as positive by both parties, we argue that they raise problems as well which warrant a discussion on how much government influence on civil society is acceptable
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