Nature communications
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Nature communications · Dec 2018
Muc5b overexpression causes mucociliary dysfunction and enhances lung fibrosis in mice.
The gain-of-function MUC5B promoter variant rs35705950 is the dominant risk factor for developing idiopathic pulmonary fibrosis (IPF). Here we show in humans that MUC5B, a mucin thought to be restricted to conducting airways, is co-expressed with surfactant protein C (SFTPC) in type 2 alveolar epithelia and in epithelial cells lining honeycomb cysts, indicating that cell types involved in lung fibrosis in distal airspace express MUC5B. ⋯ We also establish the ability of the mucolytic agent P-2119 to restore MCC and to suppress bleomycin-induced lung fibrosis in the setting of Muc5b overexpression. Our findings suggest that mucociliary dysfunction might play a causative role in bleomycin-induced pulmonary fibrosis in mice overexpressing Muc5b, and that MUC5B in distal airspaces is a potential therapeutic target in humans with IPF.
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Abstract
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Nature communications · Oct 2018
Long time-scales in primate amygdala neurons support aversive learning.
Associative learning forms when there is temporal relationship between a stimulus and a reinforcer, yet the inter-trial-interval (ITI), which is usually much longer than the stimulus-reinforcer-interval, contributes to learning-rate and memory strength. The neural mechanisms that enable maintenance of time between trials remain unknown, and it is unclear if the amygdala can support time scales at the order of dozens of seconds. ⋯ Additionally, pairs of amygdala-cingulate neurons synchronize during specific periods suggesting a shared circuit that maintains the long temporal gap. The results extend the known roles of this circuit and suggest a mechanism that maintains trial-structure and temporal-contingencies for learning.
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Nature communications · Oct 2018
Large increase in global storm runoff extremes driven by climate and anthropogenic changes.
Weather extremes have widespread harmful impacts on ecosystems and human communities with more deaths and economic losses from flash floods than any other severe weather-related hazards. Flash floods attributed to storm runoff extremes are projected to become more frequent and damaging globally due to a warming climate and anthropogenic changes, but previous studies have not examined the response of these storm runoff extremes to naturally and anthropogenically driven changes in surface temperature and atmospheric moisture content. Here we show that storm runoff extremes increase in most regions at rates higher than suggested by Clausius-Clapeyron scaling, which are systematically close to or exceed those of precipitation extremes over most regions of the globe, accompanied by large spatial and decadal variability. These results suggest that current projected response of storm runoff extremes to climate and anthropogenic changes may be underestimated, posing large threats for ecosystem and community resilience under future warming conditions.