Reassessing the role of the NLRP3 inflammasome during pathogenic influenza A virus infection via temporal inhibition.

The inflammasome NLRP3 is activated by pathogen associated molecular patterns (PAMPs) during infection, including RNA and proteins from influenza A virus (IAV). However, chronic activation by danger associated molecular patterns (DAMPs) can be deleterious to the host. We show that blocking NLRP3 activation can be either protective or detrimental at different stages of lethal influenza A virus (IAV). Administration of the specific NLRP3 inhibitor MCC950 to mice from one day following IAV challenge resulted in hypersusceptibility to lethality. In contrast, delaying treatment with MCC950 until the height of disease (a more likely clinical scenario) significantly protected mice from severe and highly virulent IAV-induced disease. These findings identify for the first time that NLRP3 plays a detrimental role later in infection, contributing to IAV pathogenesis through increased cytokine production and lung cellular infiltrates. These studies also provide the first evidence identifying NLRP3 inhibition as a novel therapeutic target to reduce IAV disease severity.

Developing human capital for successful implementation of international marine scientific research projects.

The oceans play a crucial role in the global environment and the sustainability of human populations, because of their involvement in climate regulation and provision of living and non-living resources to humans. Maintenance of healthy oceans in an era of increasing human pressure requires a high-level understanding of the processes occurring in the marine environment and the impacts of anthropogenic activities. Effective protection and sustainable resource management must be based, in part, on knowledge derived from successful research. Current marine research activities are being limited by a need for high-quality researchers capable of addressing critical issues in broad multidisciplinary research activities. This is particularly true for developing countries which will require the building of capacity for marine scientific research. This paper reviews the current activities aimed at increasing marine research capacity in developing and emerging countries and analyses the challenges faced, including: appropriate alignment of the research goals and societal and policy-relevant needs; training in multidisciplinary research; increasing capacity for overall synthesis of scientific data; building the capacity of technical staff; keeping highly qualified personnel in marine scientific research roles; cross-cultural issues in training; minimising duplication in training activities; improving linkages among human capital, project resources and infrastructure. Potential solutions to these challenges are provided, along with some priorities for action aimed at improving the overall research effort.