bims-ciryme 2019-02-24 papers

Cell Metab. 2019 Feb 11. pii: S1550-4131(19)30007-5. [Epub ahead of print]

Oxygen and Carbon Dioxide Rhythms Are Circadian Clock Controlled and Differentially Directed by Behavioral Signals.

Yaarit Adamovich, Benjamin Ladeuix, Jonathan Sobel, Gal Manella, Adi Neufeld-Cohen, Mohammad H Assadi, Marina Golik, Yael Kuperman, Ariel Tarasiuk, Maarten P Koeners, Gad Asher.

Daily rhythms in animal physiology are driven by endogenous circadian clocks in part through rest-activity and feeding-fasting cycles. Here, we examined principles that govern daily respiration. We monitored oxygen consumption and carbon dioxide release, as well as tissue oxygenation in freely moving animals to specifically dissect the role of circadian clocks and feeding time on daily respiration. We found that daily rhythms in oxygen and carbon dioxide are clock controlled and that time-restricted feeding restores their rhythmicity in clock-deficient mice. Remarkably, day-time feeding dissociated oxygen rhythms from carbon dioxide oscillations, whereby oxygen followed activity, and carbon dioxide was shifted and aligned with food intake. In addition, changes in carbon dioxide levels altered clock gene expression and phase shifted the clock. Collectively, our findings indicate that oxygen and carbon dioxide rhythms are clock controlled and feeding regulated and support a potential role for carbon dioxide in phase resetting peripheral clocks upon feeding.

Keywords: carbon dioxide; circadian clocks; metabolic cages; metabolism; oxygen; phase resetting; respiration; time restricted feeding

DOI: https://doi.org/10.1016/j.cmet.2019.01.007

Brain Res. 2019 Feb 13. pii: S0006-8993(19)30098-8. [Epub ahead of print]

Slow shift of dead zone after an abrupt shift of the light-dark cycle.

Mamoru Nagano, Keisuke Ikegami, Yoichi Minami, Yuji Kanazawa, Satoshi Koinuma, Mitsugu Sujino, Yasufumi Shigeyoshi.

The suprachiasmatic nucleus (SCN) is the center of the mammalian circadian system. Environmental photic signals shifts the phase of the circadian rhythm in the SCN except during the dead zone, when the photic signal is gated somewhere on the way from the retina to the neurons in the SCN. Here we examined the phase of the dead zone after an abrupt delay of the LD cycles for several days by observing the mc-Fos induction in the SCN by light pulses. After an abrupt shift of the LD cycles, the dead zone showed a slow phase shift, about two hours per day, which was well corresponded with the slow phase shift of the rest-activity cycles. In our previous study we demonstrated that, after an abrupt shift of the LD cycles, the SCN showed transient endogenous desynchronization between shell and core regions that showed a slow and a rapid shift of the circadian rhythms, respectively. Therefore, the present findings on the phase shift of the dead zone after the LD cycles shift suggest that the phase of the dead zone is under the control of the timing signals from the shell region of the SCN.

Keywords: VIP; c-Fos; circadian; dead zone; phase shift; suprachiasmatic nucleus

DOI: https://doi.org/10.1016/j.brainres.2019.02.014

PLoS Comput Biol. 2019 Feb 19. 15(2): e1006787

A saturated reaction in repressor synthesis creates a daytime dead zone in circadian clocks.

Koichiro Uriu, Hajime Tei.

Negative feedback loops (NFLs) for circadian clocks include light-responsive reactions that allow the clocks to shift their phase depending on the timing of light signals. Phase response curves (PRCs) for light signals in various organisms include a time interval called a dead zone where light signals cause no phase shift during daytime. Although the importance of the dead zone for robust light entrainment is known, how the dead zone arises from the biochemical reactions in an NFL underlying circadian gene expression rhythms remains unclear. In addition, the observation that the light-responsive reactions in the NFL vary between organisms raises the question as to whether the mechanism for dead zone formation is common or distinct between different organisms. Here we reveal by mathematical modeling that the saturation of a biochemical reaction in repressor synthesis in an NFL is a common mechanism of daytime dead zone generation. If light signals increase the degradation of a repressor protein, as in Drosophila, the saturation of repressor mRNA transcription nullifies the effect of light signals, generating a dead zone. In contrast, if light signals induce the transcription of repressor mRNA, as in mammals, the saturation of repressor translation can generate a dead zone by cancelling the influence of excess amount of mRNA induced by light signals. Each of these saturated reactions is located next to the light-responsive reaction in the NFL, suggesting a design principle for daytime dead zone generation.

DOI: https://doi.org/10.1371/journal.pcbi.1006787

Biosystems. 2019 Feb 18. pii: S0303-2647(18)30209-0. [Epub ahead of print]

Computational Modeling and Analysis of the Impacts of Sleep Deprivation on Glucose Stimulated Insulin Secretion.

Hufsah Ashraf, Jamil Ahmad, Azka Hassan, Amjad Ali.

Circadian clock is an exquisite internal biological clock functioning in all living organisms. Lifestyle changes such as shift work or frequent travelling might result in malfunctioning of the central and consequently the peripheral clocks leading to different metabolic disorders. Disruptions in β cell clock have been found to be a potential reason behind β cell failure that makes a person prone towards developing Type 2 Diabetes (T2DM). In this study, a Petri net model for β cell circadian clock has been developed, followed by analysis of the negative impacts of sleep deprivation conditions on the process of glucose stimulated insulin secretion (GSIS) through misalignment of circadian clock. The analysis of structural properties of the Petri net model reveals robustness of the circadian system. The simulation results predict that sleep loss negatively affects the expression of circadian genes which eventually leads to impaired GSIS and β cell failure. These results suggest that sleep/wake cycle is a vital contributor for the entrainment of the circadian clock and normal functioning of β cell.

Keywords: Circadian clock; GSIS; Sleep Deprivation; Type 2 Diabetes Mellitus; β cell failure

DOI: https://doi.org/10.1016/j.biosystems.2019.02.005