Our group recently characterized a cell-autonomous mammalian 12-h clock independent from the circadian clock, but its function and mechanism of regulation remain poorly understood. Here, we show that in mouse liver, transcriptional regulation significantly contributes to the establishment of 12-h rhythms of mRNA expression in a manner dependent on Spliced Form of X-box Binding Protein 1 (XBP1s). Mechanistically, the motif stringency of XBP1s promoter binding sites dictates XBP1s's ability to drive 12-h rhythms of nascent mRNA transcription at dawn and dusk, which are enriched for basal transcription regulation, mRNA processing and export, ribosome biogenesis, translation initiation, and protein processing/sorting in the Endoplasmic Reticulum (ER)-Golgi in a temporal order consistent with the progressive molecular processing sequence described by the central dogma information flow (CEDIF). We further identified GA-binding proteins (GABPs) as putative novel transcriptional regulators driving 12-h rhythms of gene expression with more diverse phases. These 12-h rhythms of gene expression are cell autonomous and evolutionarily conserved in marine animals possessing a circatidal clock. Our results demonstrate an evolutionarily conserved, intricate network of transcriptional control of the mammalian 12-h clock that mediates diverse biological pathways. We speculate that the 12-h clock is coopted to accommodate elevated gene expression and processing in mammals at the two rush hours, with the particular genes processed at each rush hour regulated by the circadian and/or tissue-specific pathways.

BackgroundAll organisms employ biological clocks to anticipate physical changes in the environment; however, the integration of biological clocks in symbiotic systems has received limited attention. In corals, the interpretation of rhythmic behaviours is complicated by the daily oscillations in tissue oxygen tension resulting from the photosynthetic and respiratory activities of the associated algal endosymbiont Symbiodinium. In order to better understand the integration of biological clocks in cnidarian hosts of Symbiodinium, daily rhythms of behaviour and gene expression were studied in symbiotic and aposymbiotic morphs of the sea-anemone Aiptasia diaphana.ResultsThe results showed that whereas circatidal (approx. 12-h) cycles of activity and gene expression predominated in aposymbiotic morphs, circadian (approx. 24-h) patterns were the more common in symbiotic morphs, where the expression of a significant number of genes shifted from a 12- to 24-h rhythm. The behavioural experiments on symbiotic A. diaphana displayed diel (24-h) rhythmicity in body and tentacle contraction under the light/dark cycles, whereas aposymbiotic morphs showed approximately 12-h (circatidal) rhythmicity. Reinfection experiments represent an important step in understanding the hierarchy of endogenous clocks in symbiotic associations, where the aposymbiotic Aiptasia morphs returned to a 24-h behavioural rhythm after repopulation with algae.ConclusionWhilst some modification of host metabolism is to be expected, the extent to which the presence of the algae modified host endogenous behavioural and transcriptional rhythms implies that it is the symbionts that influence the pace. Our results clearly demonstrate the importance of the endosymbiotic algae in determining the timing and the duration of the extension and contraction of the body and tentacles and temporal gene expression.Electronic supplementary materialThe online version of this article (10.1186/s40168-018-0465-9) contains supplementary material, which is available to authorized users.

Intertidal inhabitants are exposed to the 24-hour solar day, and the 12.4 hour rising and falling of the tides. One or both of these cycles govern intertidal organisms’ behaviour and physiology, yet little is known about the molecular clockworks of tidal rhythmicity. Here, we show that the limpet Cellana rota exhibits robust tidally rhythmic behaviour and gene expression. We assembled a de-novo transcriptome, identifying novel tidal, along with known circadian clock genes. Surprisingly, most of the putative circadian clock genes, lack a typical rhythmicity. We identified numerous tidally rhythmic genes and pathways commonly associated with the circadian clock. We show that not only is the behaviour of an intertidal organism in tune with the tides, but so too are many of its genes and pathways. These findings highlight the plasticity of biological timekeeping in nature, strengthening the growing notion that the role of ‘canonical’ circadian clock genes may be more fluid than previously thought, as exhibited in an organism which has evolved in an environment where tidal oscillations are the dominant driving force.

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Both time of the day and season have been shown to have a significant effect on stroke incidence. In contrast, the role played by the moon has been little studied. We aimed to investigate the potential association of the lunar phase with the incidence of stroke subtypes [intracerebral hemorrhage (ICH), transient ischemic attack (TIA) and ischemic stroke (IS)], adjusted by circadian and seasonal variations. Consecutive stroke admissions to the Royal Melbourne Hospital (RMH) were analyzed from 2004-2011. Of 6252 patients, 4085 (65.3%) had confirmed dates and hour of the day. Of these, 632 (15.5%) had ICH, 658 (16.1%) presented with TIA and 2202 (53.9%) had IS. There were also 593 (14.5%) stroke mimics. We measured the association of stroke incidence with a particular lunar phase using an incidence rate ratio (IRR) with 95% confidence intervals (CI) using Poisson regression model (new moon set as reference). Compared with new moon phase, ICHs occurred significantly more during the first quarter (IRR, 1.55; 95%CI, 1.04 to 2.30; p = 0.03). More TIAs were observed during the first quarter and full moon than in new moon (IRR, 1.69; 95%CI, 1.16 to 2.46; p = 0.01; IRR, 1.52; 95%CI, 0.00 to 2.31; p = 0.05; respectively). Both ICH and TIA occurrence slightly decreased as lunar illumination increased (IRR, 0.99; 95%CI, 0.99 to 1.00; p = 0.01; IRR, 0.99; 95%CI, 0.99 to 1.00; p = 0.04; respectively). No association was found between lunar phase or illumination and IS. All stroke subtypes were less likely to happen between 12AM and 6AM than the remaining 18 h of the day. IS occurrence was significantly higher during the spring than summer (IRR, 1.14; 95%CI, 1.02 to 1.28; p = 0.03). For the patients older than 65 years, incidence of both ICH and IS was higher in spring than in summer (IRR, 1.33; 95%CI, 1.01 to 1.74; p = 0.04; IRR, 1.22; 95%CI, 1.06 to 1.39; p = 0.005; respectively). The lunar phase and illumination are associated with both ICH and TIA incidence. These findings should be tested on other stroke databases.

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Prediction markets have been shown to generate fairly accurate odds of various events occurring in the future. The forthcoming possibility of natural disasters provides, on occasion, an opportunity for a bet, yet no wide scale and accepted prediction market has arisen despite its obvious importance, probably due in part to its 'politically incorrect' nature, but more importantly to the fact that we have yet to develop accurate forecasting models. Animals, however, have been forced through natural selection to develop elaborate anticipatory mechanisms to predict possible upcoming calamites. Recent studies suggest that animals can, days and sometimes weeks in advance, predict the occurrence of earthquakes. A wealth of recent observations and laboratory studies corroborate this. Natural disasters have lead to the development of 'risk taking' behaviors when the 'odds' of an upcoming disaster outweigh the benefits of maintaining territory, mating, and other basic behaviors. For various historical reasons discussed in this review, this field has had trouble coming of age, with little funding and support from the scientific community. Due to the great odds at stake and the tremendous economic impact of earthquakes we wish to raise the awareness of this vital topic to the wider scientific community. We present a review of such animal predictive behavior and propose that an early “reading” of such models might lead to the development of a predictions market by humans."For five days before Helike disappeared all the mice and martens and snakes and centipedes and beetles and every other creature of that kind in the town left in a body by the road that leads to Keryneia. And the people of Helike seeing this happening were filled with amazement, but were unable to guess the reason. But after the aforesaid creatures had departed, an earthquake occurred in the night; the town collapsed; an immense wave poured over it, and Helike disappeared..."Aelian (373 BC)

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