Chrotacumines G–J,chromone alkaloids from Dysoxylum acutangulum with osteoclast differentiation inhibitory activity

Four new chromone alkaloids, chrotacumines G–J (1–4), have been isolated from the barks of Dysoxylum acutangulum. Their structures and absolute configurations were elucidated on the basis of NMR and CD data. Chrotacumines G and J (1 and 4) showed osteoclast differentiation inhibitory activity in a dose dependent manner.     

Circadian Rhythms in 6-Sulphatoxymelatonin and Nocturnal Sleep in Blind Children

This article describes the relationship between melatonin secretion and sleep quality and subjective complaints about sleep in totally blind children. Eleven boarding-school children (mean age 15.2 years) participated. The major urinary melatonin metabolite 6-sulphatoxymelatonin (aMT6s) was measured five times a day for 48 h. Sleep-wake cycles were recorded by continuous actigraphic recordings during the same time period. Results showed that delayed secretory peaks in aMT6s were significantly associated with disturbed nocturnal sleep and with complaints about morning fatigue.     

White and Amber Light at Night Disrupt Sleep Physiology in Birds

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The effect of restricted feeding on the wheel-running activity rhythms of the predatory marsupial Dasyurus viverrinus

Summary The effects of restricted feeding schedules on the circadian rhythms of wheel-running of Dasyurus viverrinus were examined under a light/dark cycle and in constant darkness (experiment 1) and in constant light (experiment 2). The results of the 2 experiments showed that: (1) in contrast to the light/dark cycle, restricted feeding is only a weak zeitgeber for the wheel-running activity rhythms of D. viverrinus; (2) restricted feeding elicits meal anticipatory activity in D. viverrinus comparable to that elicited by restricted feeding in the rat; (3) transient cycles of the anticipatory activity free-run with a period different to that of the main component of activity for several cycles after the termination of restricted feeding; and (4) activity suggestive of beating between 2 oscillators occurs during restricted feeding and after the termination of restricted feeding. Taken together the latter 3 observations suggest that the activity rhythms of D. viverrinus are controlled by at least 2 separate circadian oscillators.     

Biological rhythms in birds — development, insights and perspectives

The aim of this review is to show that probably the internal clock of precocial birds is imprinted in the prenatal period by exogenous factors (zeitgeber). The activity of organ functions occurs early during embryonic development, before this function is ultimately necessary to ensure the survival of the embryo. Prenatal activation of some functional systems may have a training effect on the postnatal efficiency.The development of physiological control systems is influenced by endogenous and exogenous factors during the late prenatal and early postnatal period: epigenetic adaptation processes play an important role in the development of animals; they have acquired characteristics which are innated but not genetically fixed. As a rule, the actual value during the determination period has a very strong influence on the set-point of the system. This will be explained using the example of thermoregulation.It is shown in detail that it seems to be possible to imprint the prenatal development of circadian rhythms by periodic changes of the light-dark cycle but not by rhythmic influence of acoustic signals.Altogether, there are more questions open than solved concerning the perinatal genesis of circadian rhythms in birds. Topics are given for the future research.     

Circadian communication between unicells?

Populations ofGonyaulax polyedra, in two different phases, about 11 h apart, were mixed, and the intensity of their spontaneous bioluminescence glow recorded for about 2 wk under conditions of constant dim (35±3 μE/m²/s) white light and constant temperature (19.0±0.3°C). The phases and amplitudes of glow signals recorded from mixed cultures were compared with those obtained from the arithmetic sum of the intensity data from two control vials. Peaks in control cultures generally remained separate, but there was a spontaneous increase in the period beginning 6–11 d after the onset of constant conditions. This did not occur in cultures in which the medium was exchanged with fresh medium every 2 d. In the actual mixes of two cultures there was a merging of the two subpeaks in the signal, which did not occur when the medium was exchanged. The results indicate that conditioning of the medium by cells may affect the period of the circadian rhythm and that this might result in a type of communication. Supported by the Deutsche Forschungsgemeinschaft; present address     

Norepinephrine Turnover in the Hypothalamus of Adult Male Rats: Alteration of Circadian Patterns by Semistarvation

Norepinephrine (NE) turnover, as estimated by 3-methoxy-4-hydroxyphenylethyleneglycol concentration, was studied in the mediobasal hypothalamus of control and semistarved adult male rats at eight time points of a 24-h period. The marked circadian periodicity of NE turnover with a peak in the dark phase in control rats is completely suppressed in semistarved rats. The average 24-h concentration of the NE precursor tyrosine in brain and of tyrosine flow into brain (calculated from plasma amino acid concentrations) is reduced in semistarved rats, but both brain tyrosine and tyrosine flow show continuing circadian fluctuations.     

Circadian rhythms in biologically closed electrical circuits of plants

The circadian clock regulates a wide range of electrophysiological and developmental processes in plants. Here, we discuss the direct influence of a circadian clock on biologically closed electrochemical circuits in vivo. The biologically closed electrochemical circuits in the leaves of C. miniata (Kaffir lily), Aloe vera and Mimosa pudica, which regulate their physiology, were analyzed using the charge stimulation method. Plants are able to memorize daytime and nighttime. Even at continuous light or darkness, plants recognize nighttime or daytime and change the input resistance. The circadian clock can be maintained endogenously and has electrochemical oscillators, which can activate ion channels in biologically closed electrochemical circuits. The activation of voltage gated channels depends on the applied voltage, electrical charge, and the speed of transmission of electrical energy from the electrostimulator to plants.     

Normal vision can compensate for the loss of the circadian clock

Circadian clocks are thought to be essential for timing the daily activity of animals, and consequently increase fitness. This view was recently challenged for clock-less fruit flies and mice that exhibited astonishingly normal activity rhythms under outdoor conditions. Compensatory mechanisms appear to enable even clock mutants to live a normal life in nature. Here, we show that gradual daily increases/decreases of light in the laboratory suffice to provoke normally timed sharp morning (M) and evening (E) activity peaks in clock-less flies. We also show that the compound eyes, but not Cryptochrome (CRY), mediate the precise timing of M and E peaks under natural-like conditions, as CRY-less flies do and eyeless flies do not show these sharp peaks independently of a functional clock. Nevertheless, the circadian clock appears critical for anticipating dusk, as well as for inhibiting sharp activity peaks during midnight. Clock-less flies only increase E activity after dusk and not before the beginning of dusk, and respond strongly to twilight exposure in the middle of the night. Furthermore, the circadian clock responds to natural-like light cycles, by slightly broadening Timeless (TIM) abundance in the clock neurons, and this effect is mediated by CRY.     

Fused heterocyclic compounds bearing bridgehead nitrogen as potent HIV-1 NNRTIs. Part 1: Design,synthesis and biological evaluation of novel 5,7-disubstituted pyrazolo[1,5-a]pyrimidine derivatives

In our continuous efforts to identify novel potent HIV-1 NNRTIs, a novel class of 5,7-disubstituted pyrazolo[1,5-a]pyrimidine derivatives were rationally designed, synthesized and evaluated for their anti-HIV activities in MT4 cell cultures. Biological results showed that most of the tested compounds displayed excellent activity against wild-type HIV-1 with a wide range of EC₅₀ values from 5.98 to 0.07 μM. Among the active compounds, 5a was found to be the most promising analogue with an EC₅₀ of 0.07 μM against wild-type HIV-1 and very high selectivity index (SI, 3999). Compound 5a was more effective than the reference drugs nevirapine (by 2-fold) and delavirdine (by 2-fold). In order to further confirm their binding target, an HIV-1 RT inhibitory assay was also performed. Furthermore, SAR analysis among the newly synthesized compounds was discussed and the binding mode of the active compound 5a was rationalized by molecular modeling studies.