As the night progressed, the EEG:EMG ratios of the HDC-ΔBmal1 mice became similar to littermate controls ( Figure S4A).
Some the HDC-ΔBmal1 mice had long (up to 40 min) periods of uninterrupted waking ( Figure 3B). The total wake time, however, of HDC-ΔBmal1 check details mice averaged over 24 hr was unchanged (693 ± 21 min versus 693 ± 12 min, unpaired two-tailed t test, p > 0.05), but over the night they spent more time awake than littermate control mice and less time awake during the day (night: 420 ± 16 min versus 461 ± 10 min, unpaired two-tailed t test, p < 0.05; day: 273 ± 9 min versus 231 ± 7 min, unpaired two-tailed t test, p < 0.05) ( Figure S4A). Throughout the 24 hr, during the wake periods, the HDC-ΔBmal1 mice had higher θ frequencies in the EEG than littermate controls (two-way ANOVA and post hoc Bonferroni, p < 0.05) ( Figure S4D). The amount of nonrapid eye movement (NREM) sleep was similar between HDC-ΔBmal1 and control GSK2118436 nmr mice ( Figure S4B) (488 ± 11 min versus 427 ± 20 min, unpaired two-tailed t test, p > 0.05), but NREM power was lower ( Figure S4E; see next section) (two-way ANOVA and post hoc Bonferroni, ∗p < 0.05). During the day, HDC-ΔBmal1 mice had more NREM episodes than controls ( Figure 3C), but these episodes were shorter ( Figure 3D) (3.5 ± 0.3 min versus 2.4 ± 0.3 min,
unpaired two-tailed t test, ∗∗p < 0.01). The amount of REM sleep in HDC-ΔBmal1 mice compared with littermate controls was higher in the day ( Figure S4C): there were more episodes ( Figure 3E), although episode duration was unchanged ( Figure 3F) (1.7 ± 0.04 min versus 1.8 ± 0.04 min, unpaired two-tailed
t test, p > 0.05); however, REM episode duration was shorter in the HDC-ΔBmal1 mice ( Figure 3F) during the night (1.6 ± 0.04 min versus 1.4 ± 0.03 min, unpaired two-tailed t test, ∗∗p < 0.01). The daytime sleep architecture of HDC-ΔBmal1 mice differed from littermate control mice ( Figure 3G). HDC-ΔBmal1 mice had more “NREM-to-REM” (39 ± 2 versus 68 ± 2, unpaired two-tailed t test, ∗∗∗p < 0.001) and “REM-to-NREM” (29 ± 1 versus 58 ± 2, unpaired two-tailed t test, Phospholipase D1 ∗∗∗p < 0.001) transitions during the day ( Figure 3G). During the night, there was no difference between genotypes in NREM-REM transitions (22 ± 3 versus 28 ± 2, unpaired two-tailed t test, p > 0.05) ( Figure 3G); however, HDC-ΔBmal1 mice had fewer wake-to-NREM transitions (29 ± 3 versus 17 ± 1, unpaired two-tailed t test, ∗∗∗p < 0.001) and vice versa (21 ± 3 versus 11 ± 1, unpaired two-tailed t test, ∗∗∗p < 0.001) ( Figure 3G), reflecting that they were awake more ( Figure 3B). Thus, sustained elevated histamine in HDC-ΔBmal1 mice changed the sleep-wake architecture. HDC-ΔBmal1 mice and littermate controls were sleep deprived for 5 hr during the start of the day [ 35].
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