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- Carisey, Alexandre F, et al.
(author)
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Nanoscale Dynamism of Actin Enables Secretory Function in Cytolytic Cells
- 2018
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In: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 28:4, s. 489-502.e9
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Journal article (peer-reviewed)abstract
- Natural killer (NK) cells are innate immune effectors that lyse virally infected and tumorigenic cells through the formation of an immunological synapse. Actin remodeling at the lytic immunological synapse is a critical requirement for multiple facets of cytotoxic function. Activating receptor and integrin signaling leads to the regulated turnover and remodeling of actin, which is required for adhesion, sustained receptor signaling, and ultimately exocytosis. NK cells undergo lytic granule exocytosis in hypodense regions of a pervasive actin network. Although these requirements have been well demonstrated, neither the dynamic regulation of synaptic actin nor its specific function, however, has been determined at a nanoscale level. Here, live-cell super-resolution microscopy demonstrates nanoscale filamentous actin dynamism in NK cell lytic granule secretion. Following cell spreading, the overall content of the branched actin network at an immune synapse is stable over time and contains branched actin fibers and discrete actin foci. Similar actin architecture is generated in cytolytic T cells, although the timescale differs from that of NK cells. Individual filament displacement leads to stochastic clearance formation and disappearance, which are independent of lytic granule positioning. Actin dynamism is dependent upon branched network formation mediated by Arp2/3 and contractility generated by myosin IIA. Importantly, the use of small-molecule inhibitors demonstrates that actin dynamism is ultimately needed for granule secretion. Thus, we describe a requirement for nanoscale actin fiber rearrangement in generating the complex actin architecture that enables lytic granule secretion.
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| 2. |
- Oliver, Tom H, et al.
(author)
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Overcoming undesirable resilience in the global food system
- 2018
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In: Global Sustainability. - : Cambridge University Press (CUP). - 2059-4798. ; 1:e9, s. 1-9
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Journal article (peer-reviewed)abstract
- Our current global food system – from food production to consumption, including manufacture, packaging, transport, retail and associated businesses – is responsible for extensive negative social and environmental impacts which threaten the long-term well-being of society. This has led to increasing calls from science–policy organizations for major reform and transformation of the global food system. However, our knowledge regarding food system transformations is fragmented and this is hindering the development of co-ordinated solutions. Here, we collate recent research across several academic disciplines and sectors in order to better understand the mechanisms that ‘lock-in’ food systems in unsustainable states.
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