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Phase separation and biorhythms control biological processes in the spatial and temporal dimensions, respectively, but mechanisms of four-dimensional integration remain elusive. Here, we identified an evolutionarily conserved XBP1s-SON axis that establishes a cell-autonomous mammalian 12-hour ultradian rhythm of nuclear speckle liquid-liquid phase separation (LLPS) dynamics, separate from both the 24-hour circadian clock and the cell cycle. Higher expression of nuclear speckle scaffolding protein SON, observed at early morning/early afternoon, generates diffuse and fluid nuclear speckles, increases their interactions with chromatin proactively, transcriptionally amplifies the unfolded protein response, and protects against proteome stress, whereas the opposites are observed following reduced SON level at early evening/late morning. Correlative Son and proteostasis gene expression dynamics are further observed across the entire mouse life span. Our results suggest that by modulating the temporal dynamics of proteostasis, the nuclear speckle LLPS may represent a previously unidentified (chrono)-therapeutic target for pathologies associated with dysregulated proteostasis.more » « less
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Abstract Thwaites and Pine Island Glaciers as well as other ice streams in West Antarctica have been changing dramatically over the past decades. Although changes in ocean conditions are likely the primary driver of these changes, it remains unclear
where other processes could cause more mass loss. By employing Automatic Differentiation and two independent ice‐sheet models, we construct maps of the sensitivity of the volume above floatation to changes in ocean‐induced melt rates, ice rigidity, basal friction, and surface mass balance. We find that changes in basal melt close to the grounding lines and along shear margins have a larger impact on the glaciers' final volume. The glaciers are sensitive to changes in basal friction on regions close to the grounding lines, while changes in ice rigidity has a larger impact along the shear margins of Pine Island. The sensitivity to surface mass balance is uniform over grounded ice.