Integrin-linked kinase regulates the rate of platelet activation and is essential for the formation of stable thrombi

BACKGROUND: Integrin-linked kinase (ILK) and its associated complex of proteins are involved in many cellular activation processes, including cell adhesion and integrin signaling. We have previously demonstrated that mice with induced platelet ILK deficiency show reduced platelet activation and aggregation, but only a minor bleeding defect. Here, we explore this apparent disparity between the cellular and hemostatic phenotypes. METHODS: The impact of ILK inhibition on integrin αII b β3 activation and degranulation was assessed with the ILK-specific inhibitor QLT0267, and a conditional ILK-deficient mouse model was used to assess the impact of ILK deficiency on in vivo platelet aggregation and thrombus formation. RESULTS: Inhibition of ILK reduced the rate of both fibrinogen binding and α-granule secretion, but was accompanied by only a moderate reduction in the maximum extent of platelet activation or aggregation in vitro. The reduction in the rate of fibrinogen binding occurred prior to degranulation or translocation of αII b β3 to the platelet surface. The change in the rate of platelet activation in the absence of functional ILK led to a reduction in platelet aggregation in vivo, but did not change the size of thrombi formed following laser injury of the cremaster arteriole wall in ILK-deficient mice. It did, however, result in a marked decrease in the stability of thrombi formed in ILK-deficient mice. CONCLUSION: Taken together, the findings of this study indicate that, although ILK is not essential for platelet activation, it plays a critical role in facilitating rapid platelet activation, which is essential for stable thrombus formation.

Analysis and manipulation of the structure of odor plumes from a piezo-electric release system and measurements of upwind flight of male Almond Moths, Cadra cautella, to pheromone plumes

We investigated the plume structure of a piezo-electric sprayer system, set up to release ethanol in a wind tunnel, using a fast response mini-photoionizaton detector. We recorded the plume structure of four different piezo-sprayer configurations: the sprayer alone; with a 1.6-mm steel mesh shield; with a 3.2-mm steel mesh shield; and with a 5 cm circular upwind baffle. We measured a 12 × 12-mm core at the center of the plume, and both a horizontal and vertical cross-section of the plume, all at 100-, 200-, and 400-mm downwind of the odor source. Significant differences in plume structure were found among all configurations in terms of conditional relative mean concentration, intermittency, ratio of peak concentration to conditional mean concentration, and cross-sectional area of the plume. We then measured the flight responses of the almond moth, Cadra cautella, to odor plumes generated with the sprayer alone, and with the upwind baffle piezo-sprayer configuration, releasing a 13:1 ratio of (9Z,12E)-tetradecadienyl acetate and (Z)-9-tetradecenyl acetate diluted in ethanol at release rates of 1, 10, 100, and 1,000 pg/min. For each configuration, differences in pheromone release rate resulted in significant differences in the proportions of moths performing oriented flight and landing behaviors. Additionally, there were apparent differences in the moths’ behaviors between the two sprayer configurations, although this requires confirmation with further experiments. This study provides evidence that both pheromone concentration and plume structure affect moth orientation behavior and demonstrates that care is needed when setting up experiments that use a piezo-electric release system to ensure the optimal conditions for behavioral observations.

Massive Open Online Courses and sustainability

Massive Open Online Courses (MOOCs) have become very popular among learners millions of users from around the world registered with leading platforms. There are hundreds of universities (and other organizations) offering MOOCs. However, sustainability of MOOCs is a pressing concern as MOOCs incur up front creation costs, maintenance costs to keep content relevant and on-going support costs to provide facilitation while a course is being run. At present, charging a fee for certification (for example Coursera Signature Track and FutureLearn Statement of Completion) seems a popular business model. In this paper, the authors discuss other possible business models and their pros and cons. Some business models discussed here are: Freemium model – providing content freely but charging for premium services such as course support, tutoring and proctored exams. Sponsorships – courses can be created in collaboration with industry where industry sponsorships are used to cover the costs of course production and offering. For example Teaching Computing course was offered by the University of East Anglia on the FutureLearn platform with the sponsorship from British Telecom while the UK Government sponsored the course Introduction to Cyber Security offered by the Open University on FutureLearn. Initiatives and Grants – The government, EU commission or corporations could commission the creation of courses through grants and initiatives according to the skills gap identified for the economy. For example, the UK Government’s National Cyber Security Programme has supported a course on Cyber Security. Similar initiatives could also provide funding to support relevant course development and offering. Donations – Free software, Wikipedia and early OER initiatives such as the MIT OpenCourseware accept donations from the public and this could well be used as a business model where learners could contribute (if they wish) to the maintenance and facilitation of a course. Merchandise – selling merchandise could also bring revenue to MOOCs. As many participants do not seek formal recognition (European Commission, 2014) for their completion of a MOOC, merchandise that presents their achievement in a playful way could well be attractive for them. Sale of supplementary material –supplementary course material in the form of an online or physical book or similar could be sold with the revenue being reinvested in the course delivery. Selective advertising – courses could have advertisements relevant to learners Data sharing – though a controversial topic, sharing learner data with relevant employers or similar could be another revenue model for MOOCs. Follow on events – the courses could lead to follow on summer schools, courses or other real-life or online events that are paid-for in which case a percentage of the revenue could be passed on to the MOOC for its upkeep. Though these models are all possible ways of generating revenue for MOOCs, some are more controversial and sensitive than others. Nevertheless unless appropriate business models are identified the sustainability of MOOCs would be problematic.

CLEC-2 and Syk in the megakaryocytic/platelet lineage are essential for development

The C-type lectin receptor CLEC-2 signals through a pathway that is critically dependent on the tyrosine kinase Syk. We show that homozygous loss of either protein results in defects in brain vascular and lymphatic development, lung inflation, and perinatal lethality. Furthermore, we find that conditional deletion of Syk in the hematopoietic lineage, or conditional deletion of CLEC-2 or Syk in the megakaryocyte/platelet lineage, also causes defects in brain vascular and lymphatic development, although the mice are viable. In contrast, conditional deletion of Syk in other hematopoietic lineages had no effect on viability or brain vasculature and lymphatic development. We show that platelets, but not platelet releasate, modulate the migration and intercellular adhesion of lymphatic endothelial cells through a pathway that depends on CLEC-2 and Syk. These studies found that megakaryocyte/platelet expression of CLEC-2 and Syk is required for normal brain vasculature and lymphatic development and that platelet CLEC-2 and Syk directly modulate lymphatic endothelial cell behavior in vitro.

Post-conflict recovery and peacebuilding

Civil wars are the most common type of large scale violent conflict. They are long, brutal and continue to harm societies long after the shooting stops. Post-conflict countries face extraordinary challenges with respect to development and security. In this paper we examine how countries can recover economically from these devastating conflicts and how international interventions can help to build lasting peace. We revisit the aid and growth debate and confirm that aid does not increase growth in general. However, we find that countries experience increased growth after the end of the war and that aid helps to make the most of this peace dividend. However, aid is only growth enhancing when the violence has stopped, in violent post-war societies aid has no growth enhancing effect. We also find that good governance is robustly correlated with growth, however we cannot confirm that aid increases growth conditional on good policies. We examine various aspects of aid and governance by disaggregating the aid and governance variables. Our analysis does not provide a clear picture of which types of aid and policy should be prioritized. We find little evidence for a growth enhancing effect of UN missions and suggest that case studies may provide better insight into the relationship between security guarantees and economic stabilization.

University teaching: recognition and reward

Teaching in universities has increased in importance in recent years which, in part, is a consequence of the change in funding of universities from block grants to student tuition fees. Various initiatives have been made which serve to raise the profile of teaching and give it greater recognition. It is also important that teaching is recognised even more fully and widely, and crucially that it is rewarded accordingly. We propose a mechanism for recognising and rewarding university teaching that is based on a review process that is supported by documented evidence whose outcomes can be fed into performance and development reviews, and used to inform decisions about reward and promotion, as well as the review of probationary status where appropriate.

Achieving and evidencing research 'impact'? Tensions and dilemmas from an ethic of care perspective

While many academics are sceptical about the 'impact agenda', it may offer the potential to re-value feminist and participatory approaches to the co-production of knowledge. Drawing on my experiences of developing a UK Research Excellence Framework (REF) impact case study based on research on young caregiving in the UK, Tanzania and Uganda, I explore the dilemmas and tensions of balancing an ethic of care and participatory praxis with research management demands to evidence 'impact' in the neoliberal academy. The participatory dissemination process enabled young people to identify their support needs, which translated into policy and practice recommendations and in turn, produced 'impact'. It also revealed a paradox of action-oriented research: this approach may bring greater emotional investment of the participants in the project in potentially negative as well as positive ways, resulting in disenchantment that the research did not lead to tangible outcomes at local level. Participatory praxis may also pose ethical dilemmas for researchers who have responsibilities to care for both 'proximate' and 'distant' others. The 'more than research' relationship I developed with practitioners was motivated by my ethic of care rather than by the demands of the audit culture. Furthermore, my research and the impacts cited emerged slowly and incrementally from a series of small grants in an unplanned, serendipitous way at different scales, which may be difficult to fit within institutional audits of 'impact'. Given the growing pressures on academics, it seems ever more important to embody an ethic of care in university settings, as well as in the 'field'. We need to join the call for 'slow scholarship' and advocate a re-valuing of feminist and participatory action research approaches, which may have most impact at local level, in order to achieve meaningful shifts in the impact agenda and more broadly, the academy.