Mitotic histone H3 phosphorylation by the NIMA kinase in Aspergillus nidulans.

Phosphorylation of histone H3 serine 10 correlates with chromosome condensation and is required for normal chromosome segregation in Tetrahymena. This phosphorylation is dependent upon activation of the NIMA kinase in Aspergillus nidulans. NIMA expression also induces Ser-10 phosphorylation inappropriately in S phase-arrested cells and in the absence of NIMX(cdc2) activity. At mitosis, NIMA becomes enriched on chromatin and subsequently localizes to the mitotic spindle and spindle pole bodies. The chromatin-like localization of NIMA early in mitosis is tightly correlated with histone H3 phosphorylation. Finally, NIMA can phosphorylate histone H3 Ser-10 in vitro, suggesting that NIMA is a mitotic histone H3 kinase, perhaps helping to explain how NIMA promotes chromatin condensation in A. nidulans and when expressed in other eukaryotes.

Simultaneous pontine and basal forebrain microinjections of carbachol suppress REM sleep.

This study was performed to test the hypothesis that cholinoceptive basal forebrain systems can significantly influence cholinoceptive pontine mechanisms known to be important for generating rapid eye movement (REM) sleep. This hypothesis was examined by microinjecting the cholinergic agonist carbachol or saline (vehicle control) into the pons, the basal forebrain, or simultaneously into the pons and basal forebrain, while quantifying the effects on sleep and wakefulness in unanesthetized, chronically instrumented cats. All microinjections were made during wakefulness and were followed by 2 or 4 hr of recording. Polygraphic records were scored for wakefulness, non-REM sleep, REM sleep, and the REM sleep-like state evoked by pontine administration of carbachol (DCarb). Dependent variables quantified following each microinjection included the percentage of recording time spent in each state, the latency to onset of non-REM, REM, and DCarb, the number of episodes per hour of each state, and the duration of the longest episode of each state. A total of 149 microinjections were made into 15 forebrain and 11 pontine sites in eight cats. Basal forebrain administration of carbachol significantly increased wakefulness. Pontine microinjection of carbachol produced a state that polygraphically and behaviorally resembled REM sleep. This REM sleep-like state occurred in amounts significantly greater than natural REM sleep. Pontine carbachol also significantly decreased wakefulness and non-REM sleep. Simultaneous injection of carbachol into the pons and basal forebrain enhanced REM sleep, but the magnitude of this enhancement was significantly less than the increase in REM sleep evoked by carbachol injection into the pons alone. The results show that cholinoceptive regions of the basal forebrain can increase wakefulness and reduce the ability of pontine carbachol to evoke the REM sleep-like state. These findings suggest that basal forebrain administration of carbachol activates an arousal-generating system that can successfully compete with the powerful cholinergic REM sleep-generating system of the pons.