208 research outputs found
Sustaining Wetlands to Mitigate Disasters and Protect People
Hurricanes, flooding, droughts. Weatherârelated disasters are dominating news cycles and causing widespread destruction, most recently with Typhoon Mangkhut and Hurricane Florence. The US had the most catastrophic hurricane season on record in 2017, with hundreds of billions of dollars in estimated damages. California is experiencing unprecedented tragedies from widespread wildfires and increased vulnerability to storms. Disasters that were once uncommon appear to be the new norm globally, and evidence suggests the frequency and impacts of extreme events will increase further with climate change
Residual active granzyme B in cathepsin Cânull lymphocytes is sufficient for perforin-dependent target cell apoptosis
Cathepsin C activates serine proteases expressed in hematopoietic cells by cleaving an N-terminal dipeptide from the proenzyme upon granule packaging. The lymphocytes of cathepsin Cânull mice are therefore proposed to totally lack granzyme B activity and perforin-dependent cytotoxicity. Surprisingly, we show, using live cell microscopy and other methodologies, that cells targeted by allogenic CD8+ cytotoxic T lymphocyte (CTL) raised in cathepsin Cânull mice die through perforin-dependent apoptosis indistinguishable from that induced by wild-type CTL. The cathepsin Cânull CTL expressed reduced but still appreciable granzyme B activity, but minimal granzyme A activity. Also, in contrast to mice with inactivation of both their granzyme A/B genes, cathepsin C deficiency did not confer susceptibility to ectromelia virus infection in vivo. Overall, our results indicate that although cathepsin C clearly generates the majority of granzyme B activity, some is still generated in its absence, pointing to alternative mechanisms for granzyme B processing and activation. Cathepsin C deficiency also results in considerably milder immune deficiency than perforin or granzyme A/B deficiency
Cytotoxic T lymphocyteâinduced killing in the absence of granzymes A and B is unique and distinct from both apoptosis and perforin-dependent lysis
Cytotoxic T lymphocyte (CTL)âinduced death triggered by the granule exocytosis pathway involves the perforin-dependent delivery of granzymes to the target cell. Gene targeting has shown that perforin is essential for this process; however, CTL deficient in the key granzymes A and B maintain the ability to kill their targets by granule exocytosis. It is not clear how granzyme ABâ/â CTLs kill their targets, although it has been proposed that this occurs through perforin-induced lysis. We found that purified granzyme B or CTLs from wild-type mice induced classic apoptotic cell death. Perforin-induced lysis was far more rapid and involved the formation of large plasma membrane protrusions. Cell death induced by granzyme ABâ/â CTLs shared similar kinetics and morphological characteristics to apoptosis but followed a distinct series of molecular events. Therefore, CTLs from granzyme ABâ/â mice induce target cell death by a unique mechanism that is distinct from both perforin lysis and apoptosis
Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial
Background
Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy
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