Journal of Biological Rhythms最新文献

The light input pathways and the molecular clock are tightly linked, with light serving as the most potent zeitgeber that entrains the clock to the external environment. Our present study focuses on the Drosophila melanogaster populations that have evolved with a precise circadian clock as a correlated response to selection for adult emergence in a narrow window of time over 335 generations. The results of our study showed that flies from populations selected for the timing of adult emergence sleep more during the night phase compared to controls. This sleep was even more enhanced when the light intensity was reduced to 1 lux under a 12 h light:12 h dark cycle. In addition, a significantly higher percentage of these flies exhibited free-running period rather than arrhythmicity compared to the control flies under constant light (1 lux). Moreover, the larvae from selected populations exhibited an increased preference toward darkness than light indicating that the effect of selection extends beyond the adult circadian light input pathway, influencing the innate circadian regulated photobehavior in larvae. We examined the transcript oscillation of the circadian photoreceptor cryptochrome (cry), along with the core clock genes period (per) and timeless (tim) in adult flies to explore the molecular basis of the evolved precise circadian clocks and to determine whether selection influences the circadian light input pathway. Flies from the selected population exhibited a phase advance in the transcript oscillation of per, tim, and cry, indicating that the molecular circadian clock and its light input pathway evolve as a correlated response to the selection for the timing of adult emergence in D. melanogaster populations.

The circadian clock in eukaryotes keeps time via transcriptional feedback loops. In the transcriptional feedback loop of animals, CLOCK activator complexes drive expression of PER repressor complex components which feedback to inhibit CLOCK activation until PER complexes are degraded, thus initiating the next round of CLOCK activation ~24 h later. Recently, we showed that a region of monarch CLOCK (CLK) analogous to that encoded by mammalian CLOCK exon 19 (CLKe19r) and the methyltransferase TRITHORAX (TRX) are required for CLK activation, PER-CLK binding, and PER repression and that TRX-dependent methylation of Heat Shock Protein 68 (HSP68) at arginine 45 (R45) is necessary for PER-CLK binding and PER repression. Given that CLK activation and PER repression complexes in Drosophila are comprised of different core components than in monarchs, we tested whether similar mechanisms are used for CLK activation and PER repression in Drosophila. We found that the CLKe19r, TRX and HSP68 are all required for CLK activation yet only HSP68, but not HSP68 R45 methylation, is required for PER repression in Drosophila. These results reveal a well-conserved CLK activation mechanism and a PER repression mechanism that retains HSP68 function but does not require TRX-dependent methylation.

While current mathematical models of human circadian rhythms accurately predict circadian phase responses to light in controlled laboratory experiments, they show reduced performance in the real world, especially among shift workers with irregular schedules and downstream erratic light diets. The source of the discrepancy between in-laboratory and ambulatory performance remains unclear. We evaluate the impact of initialization strategy, recording duration, and light exposure characteristics on model performance using wearable data from both individuals on regular schedules and shift workers. We implement a probabilistic initialization framework to account for unknown starting phase and assess model performance in prediction of phase from light input data against an in-lab measure of circadian phase (dim light melatonin onset). In participants with regular schedules, accuracy improved with longer recordings, while shift workers show no accuracy gains when having more nights of data. Light exposure patterns differed significantly between groups, with brighter and more regular day-to-day light exposure being weakly to moderately associated with improved model estimates, whereas fragmented patterns of light exposure increased uncertainty. These findings suggest that current models require adaptation, particularly in light sensitivity, to generalize to free-living, irregular conditions and support robust, scalable circadian tracking in real-world populations.

Sepsis is a syndrome caused by a dysregulated host response to pathogens, representing the leading cause of death from infection. Various murine models of sepsis have shown a time-dependent response based on the time of induction. Mice stimulated with high doses of bacterial lipopolysaccharide (LPS) at the end of the day exhibit a higher mortality rate (~80%) compared with those inoculated in the middle of the night (~30%). In this work, we assessed the differences in serum proteins of septic mice during the day and night. Through this proteomic study, we found significant variations in metabolic pathways, including glucose metabolism, which were associated with a better prognosis. Therefore, we studied the glucose response to LPS during the day and night. In this context, we found an early peak of LPS-induced glucose exclusively at the time of worse prognosis. We also observed a hypoglycemic response to LPS, which was independent of the time of sepsis induction. Finally, we performed a set of metabolic manipulations to study how hyperglycemia influences sepsis severity in mice. We observed that suppressing the glucose peak during the day, through metformin administration, reduced sepsis severity. In contrast, nocturnal glucose administration with LPS was rapidly metabolized and also decreased sepsis severity. In conclusion, sepsis severity may be influenced by the metabolic state at the time of the stimulus. Metabolic rhythms could lead to differences in early glucose management, affecting the outcome of this pathology.

Animals often show distinct activity rhythms which may align their behavior with favorable environmental conditions. In terrestrial species, daily and seasonal activity patterns are largely influenced by changes in photoperiod and temperature. However, subterranean animals experience weak or absent environmental variation due to minimal light exposure and reduced daily temperature fluctuations. Despite these conditions, many subterranean rodents display pronounced diel rhythms in physiological processes and locomotor activity, though the extent of seasonal variation remains unclear. In this study, we used radio frequency identification technology on wild groups of subterranean Damaraland mole-rats to assess their daily activity patterns. Our results show a population-wide daily activity peak around midday, which coincides with the minimum temperature at nesting depths and increasing temperature at foraging depths. The timing of this peak shifts by approximately 2 h between seasons. Neither individual nor group characteristics predicted the occurrence and timing of the activity peak, suggesting that temperature fluctuations, rather than social factors, are the main driver of seasonal variation in activity timing. Although Damaraland mole-rats remain active at low levels throughout the day, they display clear diurnal foraging rhythms at the group level that change little across seasons.

Early childhood represents a period of profound developmental changes for sleep and circadian biology. Although the relationship between sleep and circadian timing has been well characterized in older populations, such data in young children remain limited. Here, we provide fundamental data on the relationship between endogenous circadian phase and sleep timing in a sample of preschool-aged children. Participants were 49 healthy children ages 3.1 to 6.0 years (M = 4.44 years, SD = 0.69 years, 27 female). After 7 days of maintaining a consistent, parent-selected sleep schedule, children completed an in-home, dim-light circadian assessment. Saliva samples were collected in 30-min intervals throughout the evening to determine the timing of children's dim-light melatonin onset (DLMO). Children's DLMOs occurred an average of 35.0 ± 35.3 min before their bedtimes, with parent-selected bedtime occurring before DLMO for 18.4% of children. Children with later DLMOs had significantly later bedtimes (r = 0.65), sleep onset times (r = 0.74), midsleep times (r = 0.74), and wake times (r = 0.66) (all p < 0.001). For every hour later that DLMO occurred, average bedtime and sleep onset time were 28.0 and 33.4 min later, respectively. In addition, children with later DLMOs had higher scores on a parent-reported measure of chronotype (r = 0.56, p < 0.001), indicating greater eveningness. No association between DLMO time and sleep duration or social jetlag was observed. These data extend previous findings in toddlers, demonstrating a consistent relationship between circadian phase and sleep timing, as well as chronotype, throughout early childhood.