Prostacyclin (PGI2) modulates platelet activation to regulate haemostasis. Evidence has emerged to suggest that thrombi are dynamic structures with distinct areas of differing platelet activation. It was hypothesised that PGI2 could reverse platelet spreading by actin cytoskeletal modulation, leading to reduced capability of platelet aggregates to withstand a high shear environment. Our data demonstrates that post-flow of PGI2 over activated and spread platelets on fibrinogen, identified a significant reduction in platelet surface area under high shear. Exploration of the molecular mechanisms underpinning this effect revealed that PGI2 reversed stress fibre formation in adherent platelets, reduced platelet spreading, whilst simultaneously promoting actin nodule formation. The effects of PGI2 on stress fibres were mimicked by the adenylyl cyclase activator forskolin and prevented by inhibitors of protein kinase A (PKA). Stress fibre formation is a RhoA dependent process and we found that treatment of adherent platelets with PGI2 caused inhibitory phosphorylation of RhoA, reduced RhoA GTP-loading and reversal of myosin light chain phosphorylation. Phospho-RhoA was localised in actin nodules with PKA type II and a number of other phosphorylated PKA substrates. This study demonstrates that PGI2 can reverse key platelet functions after their initial activation and identifies a novel mechanism for controlling thrombosis.

Citizen engagement and participation are a key focus for government and government agencies, and with the advent of Internet technologies questions arise about the role and impact of technology on citizen participation. This paper aims to explore the role of technology in citizen participation within schools. This research used in-depth comparative case studies using examples from two different schools and school systems, one in the United Kingdom and one in Indonesia. The wider school systems are complex and dynamic environments with multiple stakeholders, media, and supporting systems, and the schools operate under geopolitical and social influences. This paper provides a framework, based on Actor-Network Theory (ANT), for capturing e-participation in schools, particularly identifying the influence of technology as a conduit for enabling, engaging, and empowering stakeholders.

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