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Fig. 3. Phase-resetting effects on the molecular oscillators by the REV-ERB ligand. Individual cultures of confluent Rat-1 cells stably transfected with Per2::Luc reporter, or primary lung fibroblasts from PER2::Luc mice were synchronized by Dex for 1 hour and monitored using PMT. Cells were then treated with the compound (10 µM, red) at a single phase point for each culture dish. Control cultures were treated with DMSO (black). (A,B,D,E) Representative traces of PMT real-time recording. Compound addition is indicated by vertical arrows and phase changes by horizontal arrows. (C,F) Ligand-induced phase-response curves (PRCs). For the PRC estimates, actual phase changes were plotted against circadian time, with the peak of PER2 expression taken as CT12. Data shown are representative of three independent experiments. Negative values indicate phase delays, whereas positive values refer to phase advances.

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