Molecular mechanism of suppression of circadian rhythms by a critical stimulus.
ABSTRACT Circadian singularity behavior (also called suppression of circadian rhythms) is a phenomenon characterized by the abolishment of circadian rhythmicities by a critical stimulus. Here we demonstrate that both temperature step up and light pulse, stimuli that activate the expression of the Neurospora circadian clock gene frequency (frq), can trigger singularity behavior in this organism. The arrhythmicity is transient and is followed by the resumption of rhythm in randomly distributed phases. In addition, we show that induction of FRQ expression alone can trigger singularity behavior, indicating that FRQ is a state variable of the Neurospora circadian oscillator. Furthermore, mutations of frq lead to changes in the amplitude of FRQ oscillation, which determines the sensitivity of the clock to phase-resetting cues. Our results further suggest that the singularity behavior is due to the loss of rhythm in all cells. Together, these data suggest that the singularity behavior is due to a circadian negative feedback loop driven to a steady state after the critical treatment. After the initial arrhythmicity, cell populations are then desynchronized.
Full-textDOI: · Available from: Guocun Huang, Apr 17, 2015
SourceAvailable from: mss3.libraries.rutgers.edu
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ABSTRACT: Modern societies are characterized by a 24/7 lifestyle (LS) with no environmental differences between day and night, resulting in weak zeitgebers (weak day light, absence of darkness during night, constant environmental temperature, sedentary LS and frequent snacking), and as a consequence, in an impaired circadian system (CS) through a process known as chronodisruption. Both weak zeitgebers and CS impairment are related to human pathologies (certain cancers, metabolic syndrome and affective and cognitive disorders), but little is known about how to chronoenhance the CS. The aim of this work is to propose practical strategies for chronoenhancement, based on accentuating the day/night contrast. For this, 131 young subjects were recruited, and their wrist temperature (WT), activity, body position, light exposure, environmental temperature and sleep were recorded under free-living conditions for 1 week. Subjects with high contrast (HC) and low contrast (LC) for each variable were selected to analyze the HC effect in activity, body position, environmental temperature, light exposure and sleep would have on WT. We found that HC showed better rhythms than LC for every variable except sleep. Subjects with HC and LC for WT also demonstrated differences in LS, where HC subjects had a slightly advanced night phase onset and a general increase in day/night contrast. In addition, theoretical high day/night contrast calculated using mathematical models suggests an improvement by means of LS contrast. Finally, some individuals classified as belonging to the HC group in terms of WT when they are exposed to the LS characteristic of the LC group, while others exhibit WT arrhythmicity despite their good LS habits, revealing two different WT components: an exogenous component modified by LS and another endogenous component that is refractory to it. Therefore, intensifying day/night contrast in subject's LS has proven to be a feasible measure to chronoenhance the CS.Chronobiology International 12/2013; DOI:10.3109/07420528.2013.861845 · 2.88 Impact Factor
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ABSTRACT: Amplitude modulation in limit cycle models of circadian clocks has been previously formulated to explain the phenomenon of temperature compensation. These models propose that invariance of clock period (τ) with changing temperature is a result of the system traversing small or large limit cycles such that despite a decrease or an increase in the linear velocity of the clock owing to slowing down or speeding up of the underlying biochemical reactions, respectively, the angular velocity and, thus, the clock period remain constant. In addition, these models predict that phase resetting behavior of circadian clocks described by limit cycles of different amplitudes at low or high temperatures will be drastically different. More specifically, this class of models predicts that at low temperatures, circadian clocks will respond to perturbations by eliciting larger phase shifts by virtue of their smaller amplitude and vice versa. Here, we present the results of our tests of this prediction: We examined the nature of photic phase response curves (PRCs) and phase transition curves (PTCs) for the circadian clocks of 4 wild-type fruit fly Drosophila melanogaster populations at 3 different ambient temperatures (18, 25, and 29 °C). Interestingly, we observed that at the low temperature of 18 °C, fly clocks respond to light perturbations more strongly, eliciting strong (type 0) PRCs and PTCs, while at moderate (25 °C) and high (29 °C) temperatures the same stimuli evoke weak (type 1) responses. This pattern of strong and weak phase resetting at low and high temperatures, respectively, renders support for the limit cycle amplitude modulation model for temperature compensation of circadian clocks.Journal of Biological Rhythms 12/2013; 28(6):380-389. DOI:10.1177/0748730413508922 · 3.32 Impact Factor