Major life transitions are always difficult because change costs energy.Recent findings have demonstrated how mitochondrial oxidative phosphorylation(OxPhos)defects increase the energetic cost of living and that exces...Major life transitions are always difficult because change costs energy.Recent findings have demonstrated how mitochondrial oxidative phosphorylation(OxPhos)defects increase the energetic cost of living and that excessive integrated stress response(ISR)signaling may prevent cellular identity transitions during development.In this perspective,we discuss general bioenergetic principles of life transitions and the costly molecular processes involved in reprograming the cellular hardware/software as cells shift identity.The energetic cost of cellular differentiation has not been directly quantified,representing a gap in knowledge.We propose that the ISR is an energetic checkpoint evolved to(i)prevent OxPhos-deficient cells from engaging in excessively costly transitions and(ii)allow ISR-positive cells to recruit systemic energetic resources by signaling via GDF15 and the brain.展开更多
What is already known about this topic?Short-term exposure to PM2.5 has been associated with population excess death.This issue is of critical concern in China given its high level of exposure to PM2.5 compared to tha...What is already known about this topic?Short-term exposure to PM2.5 has been associated with population excess death.This issue is of critical concern in China given its high level of exposure to PM2.5 compared to that of the rest of the world.What is added by this report?Existing studies were conducted from 2013-2015 and have failed to capture the full effects of China’s actions towards cleaner air in recent years,such as the first Action Plan for Air Pollution Prevention and Control issued in 2013.This study uses the longest time series data to date from 2013-2018,provides the latest evidence on PM2.5 and cause-specific death nationwide,and identifies regional patterns of PM2.5-related effects as well as PM2.5-related susceptible populations.What are the implications for public health practice?This study suggests that the development of standards and the implementation of actions to clean the air and protect public health should be tailored to PM2.5-related sensitive diseases,susceptible populations,and regional patterns.展开更多
基金supported by grants from the NIH(R01MH119336,R01MH122706,R01AG066828,and RF1AG076821)the Wharton Fund,and the Baszucki Brain Research Fund to M.P.M.L.gratefully acknowledges support from the Templeton World Charity Foundation(TWCF0606)the Bill and Melinda Gates Foundation.
文摘Major life transitions are always difficult because change costs energy.Recent findings have demonstrated how mitochondrial oxidative phosphorylation(OxPhos)defects increase the energetic cost of living and that excessive integrated stress response(ISR)signaling may prevent cellular identity transitions during development.In this perspective,we discuss general bioenergetic principles of life transitions and the costly molecular processes involved in reprograming the cellular hardware/software as cells shift identity.The energetic cost of cellular differentiation has not been directly quantified,representing a gap in knowledge.We propose that the ISR is an energetic checkpoint evolved to(i)prevent OxPhos-deficient cells from engaging in excessively costly transitions and(ii)allow ISR-positive cells to recruit systemic energetic resources by signaling via GDF15 and the brain.
基金funded by National Key Research and Development Program of China(No.2016YFC0206500)National research program for key issues in air pollution control(No.DQGG0401).
文摘What is already known about this topic?Short-term exposure to PM2.5 has been associated with population excess death.This issue is of critical concern in China given its high level of exposure to PM2.5 compared to that of the rest of the world.What is added by this report?Existing studies were conducted from 2013-2015 and have failed to capture the full effects of China’s actions towards cleaner air in recent years,such as the first Action Plan for Air Pollution Prevention and Control issued in 2013.This study uses the longest time series data to date from 2013-2018,provides the latest evidence on PM2.5 and cause-specific death nationwide,and identifies regional patterns of PM2.5-related effects as well as PM2.5-related susceptible populations.What are the implications for public health practice?This study suggests that the development of standards and the implementation of actions to clean the air and protect public health should be tailored to PM2.5-related sensitive diseases,susceptible populations,and regional patterns.
