Palladium-catalyzed double alkylation of 3-aryl-2-fluoroallyl esters with malonate nucleophiles through the carbon-fluorine bond cleavage.

The alkylation of (Z)-3-aryl-2-fluoroallyl acetate with the malonate anion by the [Pd(C3H5)(cod)]BF4/2,2'-bpy catalyst proceeds through the carbon-fluorine bond cleavage, and 2 equiv of the malonate nucleophile was introduced to the allyl substrate.

Ruthenium-catalyzed regio- and stereoselective addition of carboxylic acids to aryl and trifluoromethyl group substituted unsymmetrical internal alkynes.

The regio- and stereoselective addition of carboxylic acids to aryl and trifluoromethyl group substituted unsymmetrical internal alkynes has been accomplished: the Ru(3)(CO)(12)/3PPh(3) catalyst system has effectively catalyzed the reaction to afford the trifluoromethyl group substituted (E)-enol esters with high regio- and stereoselectivities.

Ruthenium-catalyzed regioselective [2 + 2 + 2] cyclotrimerization of trifluoromethyl group substituted internal alkynes.

It found that the Ru(3)(CO)(12) coordinated with 2-(diphenylphosphino)benzonitrile (2-DPPBN) to effectively catalyze the [2 + 2 + 2] cyclotrimerization of the trifluoromethyl group substituted internal alkynes in high yields with up to >98% regioselectivity. Isolation of a ruthenacyclopentadiene was successful and confirmed that the complex is a reaction intermediate.

Theta wave amplitude and frequency are differentially correlated with pontine waves and rapid eye movements during REM sleep in rats.

The present study examined the correlations between the dynamics of hippocampal theta waves and pontine waves (P waves) and rapid eye movements (REMs) densities during REM sleep. Theta wave peak frequency and theta amplitude were estimated as the parameters of theta wave dynamics in each 3s segment. The peak frequency and theta amplitude were positively correlated with P wave and REMs densities, however their detailed correlation properties were distinct from each other. Dependency of peak frequency on P wave/REMs density did not change significantly from that on REMs/P wave density. On the other hand, dependency of the theta amplitude on P wave/REMs density significantly increased with an increased REMs/P wave density. Because hippocampal theta waves and P waves are involved in learning and memory functions during REM sleep, the correlation between theta parameters and P wave density might help to clarify these functions.

Modeling interactions between photic and nonphotic entrainment mechanisms in transmeridian flights.

In transmeridian flights, photic and nonphotic entrainment mechanisms are expected to interact dynamically in the human circadian system. In order to simulate the reentrainment process of the circadian rhythms, the photic entrainment mechanism was introduced to our previous model, which consisted of three coupled oscillators. Regardless of flight direction, a large time difference beyond 10 h tended to induce the antidromic reentrainment. The partition between the oscillators resulted for the eastward flight over a 10-h or longer time difference and the westward over 6 h or longer. The simulated reentrainment processes almost coincided with empirical knowledge. Simulated effects of physical exercise showed that some antidromic reentrainments were switched to the orthodromic ones for the eastward flight and most of the partitions between the oscillators were prevented in the westward flight. These results are due to an augmentation of the entrainment pressure of the rest-activity cycle on the oscillators. The mechanisms underlying these various reentrainment patterns were explained based on the photic response, the interactions between the oscillators, and their adaptive modification. The simulation results suggest that an appropriate selection of departure time and physical exercise could ease the jet lag caused by transmeridian flight.

Is state-dependent alternation of slow dynamics in central single neurons during sleep present in the rat ventroposterior thalamic nucleus?

Based upon our previous results in cats, we hypothesized that neurons in the central processor systems of the brain generally exhibit state-dependent dynamics alternation of slow fluctuations in spontaneous activity during sleep. To test the validity of this hypothesis across species, we recorded single neuronal activity during sleep from the ventroposterior (VP) thalamic nucleus in unanesthetized, head-restrained rats. Spectral analysis was performed on successive spike-counts of neuronal activity recorded during three stages of the sleep-wakefulness cycle: wakefulness (W, n=6), slow-wave sleep (SWS, n=20), and paradoxical sleep (PS, n=32). We found that firing of VP neurons displayed white-noise-like dynamics over the range of 0.04-1.0 Hz during SWS and 1/f-noise-like dynamics over the same range during PS. We also demonstrated for the first time that the slow dynamics of neuronal activity during quiet wakefulness (but not drowsiness) are white-noise-like. These results suggest that our hypothesis is true across species. During W and SWS, the brain may be considered as under global inhibition. Conversely, PS may represent a state of global disinhibition in the brain, where neuronal activity exhibits 1/f-noise-like dynamics. Fluctuations observed in living organisms may be involved in essential processes in generation and function of sleep states.

Phase-locking of spontaneous and elicited ponto-geniculo-occipital waves is associated with acceleration of hippocampal theta waves during rapid eye movement sleep in cats.

We investigated the temporal relationship between hippocampal theta waves and ponto-geniculo-occipital waves (PGO) during rapid eye movement sleep (REM sleep) in cats. In addition, we analyzed the relationship between hippocampal theta waves and PGO as elicited by tone stimulus (PGO(E)) in order to quantitively characterize the PGO wave generator mechanism. The results showed that a spontaneous PGO tended to be phase-locked to the theta wave, which was more clearly observed in the single PGO than in the cluster. However, cluster PGO(E) tended to be phase-locked as well as single PGO(E). It was therefore suggested that the generator of PGO is activated in relation to the hippocampal theta wave. An acceleration of the theta wave associated with PGO occurrence was found, and was more markedly observed than with the cluster PGO. Although the magnitude of it was less than in the spontaneous case, an acceleration around the PGO(E) was also observed. These results suggest that the generators of theta and PGO receive some common activations, especially when a cluster PGO is generated. The interaction between PGO and hippocampal theta waves is expected to be involved in the possible functions of REM sleep.

A phase dynamics model of human circadian rhythms.

Nonphotic entrainment of an overt sleep-wake rhythm and a circadian pacemaker-driving temperature/melatonin rhythm suggests existence of feedback mechanisms in the human circadian system. In this study, the authors constructed a phase dynamics model that consisted of two oscillators driving temperature/melatonin and sleep-wake rhythms, and an additional oscillator generating an overt sleep-wake rhythm. The feedback mechanism was implemented by modifying couplings between the constituent oscillators according to the history of correlations between them. The model successfully simulated the behavior of human circadian rhythms in response to forced rest-activity schedules under free-run situations: the sleep-wake rhythm is reentrained with the circadian pacemaker after release from the schedule, there is a critical period for the schedule to fully entrain the sleep-wake rhythm, and the forced rest-activity schedule can entrain the circadian pacemaker with the aid of exercise. The behavior of human circadian rhythms was reproduced with variations in only a few model parameters. Because conventional models are unable to reproduce the experimental results concerned here, it was suggested that the feedback mechanisms included in this model underlie nonphotic entrainment of human circadian rhythms.

Effects of orexin on the laterodorsal tegmental neurones.

Orexin, a hypothalamic neuropeptide, has been revealed to be involved in sleep regulation. To elucidate functions of orexin in brainstem sleep regulation mechanism, we examined the effects of orexin applied from micropipettes with air pressure on neurones in and around the laterodorsal tegmental nucleus (LDT). In five of seven cholinergic neurones and six of nine non-cholinergic neurones orexin induced long-lasting excitation. These results suggest that hypothalamic orexin neurones may affect the LDT neurones directly, and thereby participate in control of sleep.

Elicited ponto-geniculo-occipital waves by auditory stimuli are synchronized with hippocampal theta-waves.

The study demonstrated that ponto-geniculo-occipital (PGO) waves are phase-locked with hippocampal theta-waves during rapid eye movement (REM) sleep. A possible mechanism for influencing a PGO wave generator by hippocampal theta-waves was hypothesized. The generator is known to receive afferent inputs such as auditory input. To test this hypothesis, the temporal relationship between hippocampal theta-waves and elicited PGO waves (PGO(E)) by auditory stimuli was analysed. The analysis showed that PGO(E) were synchronized with theta-waves, but did not reset the phase of a theta-wave. Because the occurrence of PGO(E) and spontaneous PGO waves shared the same phase-dependency on theta-waves, the results strongly suggest that the PGO wave generator was driven by theta-waves, as originally hypothesized.

Phase shift of coupled oscillator model with feedbacks in response to multiple bright light exposure.

Human temperature rhythm was reported to have type 0 phase response curve (PRC) to multiple bright light exposure; however, mechanisms underlying this finding could not be clarified easily in a theoretical framework, and has not yet been confirmed by other researchers. In this paper, under reproduced photic exposure, phase response properties of a coupled three oscillator model were investigated to identify the possible mechanism underlying the experimental finding. The resulting phase shift of an oscillator reached approximately 12 h, and changed its sign acutely at the cross-over point of an original PRC of the oscillator. This type 0-like phase shift was produced by an accumulated phase response during the oscillator's re-entrainment process to the photic exposure. The organization of coupled oscillators affected the total amount of this phase shift.

Upregulation of stress response mRNAs in COS-7 cells exposed to cadmium.

Exposure of cells to cadmium (Cd) is known to stimulate the expression of various types of genes. These changes in gene expression are presumed to be related to the cellular response to Cd toxicity. To better understand the mechanisms related to Cd toxicity, suppression subtractive hybridization was carried out on COS-7 cells (African green monkey kidney cells) and the gene expression induced by Cd exposure was investigated. Heat shock protein (hsp) 10, 40, 60, 70, 89alpha and metallothionein II (MTII) mRNAs were found to be induced by Cd. This is the first report to describe the Cd-inducibility of hsp10, 40 and 89alpha mRNAs. Semi-quantitative reverse-transcription polymerase chain reaction showed the diverse expression patterns of these genes, depending on Cd concentration and exposure time. A marked elevation of hsp70 mRNA and induction of mRNA for the co-chaperone, hsp40, were detected. A relatively low level of hsp10 and hsp60 mRNAs was induced, with only a 2-fold increase within 24 h. Hsp89alpha mRNA was induced shortly after Cd exposure. These various induction patterns suggest that hsps play different roles in the cell against Cd toxicity.

Effects of morphine on two types of nucleus raphe dorsalis neurons in awake cats.

Forty-nine neurons recorded within the nucleus raphe dorsalis (NRD) in awake cats were classified into 2 groups: 29 regularly firing (clock-like) and 20 irregularly firing (non-clock-like) neurons. Hardly any of the clock-like neurons were influenced either by noxious stimulation (0.1 ml of 5% formalin, s.c.) or by a single dose (1 mg/kg, i.p.) or cumulative doses (0.25, 0.5, 1 mg/kg) of morphine. In contrast, about half the non-clock-like neurons were activated both by noxious stimulation and by administration of morphine. Morphine-induced activation of non-clock-like neurons was dose-related and reversed by naloxone (0.2 mg/kg, i.p.). These findings suggest that clock-like neurons in the NRD are not involved in morphine analgesia. Non-clock-like neurons, however, may play a role in the mediation of such analgesia.

An improved radiant heat algometer and its application to pain threshold measurements in man.

A radiant heat algometer system is described which enables the psychophysical and clinical study of cutaneous pain sensations and reactions by means of a precise, stabilized power source. In this system DC electric power consumption of a bulb is automatically controlled, and no calibration is necessary to be controlled frequently. Moreover, attention is drawn to the significance of using the blackened sticky tape and of the pre-heating procedure. The application of this algometer is also described for a pain threshold determination with the intensity and time methods.