Cryptochrome-1 regulates the ecdysone titer to influence the emergence rhythm of Bactrocera dorsalis.

Circadian Time-Place Learning in Mice Depends on Cry Genes

Light-Mediated TIM Degradation within Drosophila Pacemaker Neurons (s-LNvs) Is Neither Necessary nor Sufficient for Delay Zone Phase Shifts

Entrainment of eclosion and preliminary ontogeny of circadian clock gene expression in the flesh fly, Sarcophaga crassipalpis

Circadian molecular clock disruption in chronic pulmonary diseases.

Autophagy of granulosa cells (GCs) is involved in follicular atresia, which occurs repeatedly during the ovarian development cycle. Several circadian clock genes are rhythmically expressed in both rodent ovarian tissues and GCs. Nuclear receptor subfamily 1 group D member 1 (NR1D1), an important component of the circadian clock system, is involved in the autophagy process through the regulation of autophagy-related genes. However, there are no reports illustrating the role of the circadian clock system in mouse GC autophagy. In the present study, we found that core circadian clock genes (Bmal1, Per2, Nr1d1, and Dbp) and an autophagy-related gene (Atg5) exhibited rhythmic expression patterns across 24 h in mouse ovaries and primary GCs. Treatment with SR9009, an agonist of NR1D1, significantly reduced the expression of Bmal1, Per2, and Dbp in mouse GCs. ATG5 expression was significantly attenuated by SR9009 treatment in mouse GCs. Conversely, Nr1d1 knockdown increased ATG5 expression in mouse GCs. Decreased NR1D1 expression at both the mRNA and protein levels was detected in the ovaries of Bmal1-/- mice, along with elevated expression of ATG5. Dual-luciferase reporter assay and electrophoretic mobility shift assay showed that NR1D1 inhibited Atg5 transcription by binding to two putative retinoic acid-related orphan receptor response elements within the promoter. In addition, rapamycin-induced autophagy and ATG5 expression were partially reversed by SR9009 treatment in mouse GCs. Taken together, our current data demonstrated that the circadian clock regulates GC autophagy through NR1D1-mediated inhibition of ATG5 expression, and thus, plays a role in maintaining autophagy homeostasis in GCs.

Both the circadian clock and sex hormone signaling can strongly influence brain function, yet little is known about how these 2 powerful modulatory systems might interact during complex neural processes like memory consolidation. Individually, the molecular components and action of each of these systems have been fairly well-characterized, but there is a fundamental lack of information about how these systems cooperate. In the circadian system, clock genes function as timekeeping molecules that convey time-of-day information on a well-stereotyped cycle that is governed by the suprachiasmatic nucleus. Keeping time is particularly important to synchronize various physiological processes across the brain and body, including those that regulate memory consolidation. Similarly, sex hormones are powerful modulators of memory, with androgens, estrogens, and progestins, all influencing memory consolidation within memory-relevant brain regions like the hippocampus. Despite clear evidence that each system can influence memory individually, exactly how the circadian and hormonal systems might interact to impact memory consolidation remains unclear. Research investigating either sex hormone action or circadian gene function within memory-relevant brain regions has unveiled several notable places in which the two systems could interact to control memory. Here, we bring attention to known interactions between the circadian clock and sex hormone signaling. We then review sex hormone-mediated control of memory consolidation, highlighting potential nodes through which the circadian system might interact during memory formation. We suggest that the bidirectional relationship between these two systems is essential for proper control of memory formation based on an animal's hormonal and circadian state.

ABSTRACTFruit flies (Drosophila melanogaster) eclose from their pupae mainly around dawn. The timing of eclosion is thought to confer adaptive benefits to the organisms and thus shows remarkable accuracy. However, it is not clear what factors are involved in the evolution of such accuracy in natural populations. In this study, we examined the relative contributions of gating of eclosion by the circadian clock versus clock-independent developmental rates and light-induced responses in the eclosion phenotype exhibited by fly populations that have evolved greater accuracy in eclosion rhythms compared to controls. We compared variation in timing of transitions between early developmental stages (pupariation and pigmentation), overall development time under constant light conditions – where circadian clocks are dysfunctional – and eclosion profiles when developmental rate was manipulated using different larval densities in selected and control stocks. Our results showed that stocks that have evolved greater accuracy of eclosion rhythms due to artificial selection do not show reduced individual variation in pupariation and pigmentation time compared to controls, though they do exhibit lower variation in eclosion time. Selected stocks also did not show lower variation in eclosion time under constant light conditions in contrast to the greater accuracy seen under light-dark cycles. Moreover, manipulations of developmental rate by varying larval density and inducing eclosion by changing onset of light phase did not alter the eclosion profile of selected stocks as much as it did controls, since selected stocks largely restricted eclosion to the daytime. These results suggest that fly populations selected for greater accuracy have evolved accurate eclosion rhythms primarily by strengthening circadian gating of eclosion rather than due to fine-tuning of clock-independent developmental processes.This article has an associated First Person interview with the first author of the paper.

Expression of circadian core clock genes in fibroblasts of human gingiva and periodontal ligament is modulated by L-Mimosine and hypoxia in monolayer and spheroid cultures

Comparison of the circadian eclosion rhythm between non-diapause and diapause pupae in the onion fly, Delia antiqua: the effect of thermoperiod

The circadian clock is involved in many physiological processes including teeth development. The expression of circadian core clock genes was observed in various tissues, but their role in odontoblasts is unclear. The aim of this study was to investigate the circadian core clock gene expressions of dental papilla cells (DPCs) during the odontogenic differentiation. Primary DPCs were obtained from the first molar dental papilla of neonatal rats and cultured in osteogenic (OS) medium for differentiation in vitro. Reverse transcription and quantitative PCR was performed to assess the mRNA levels of the circadian core clock genes Bmal1, Per2, Cry1, Clock, Rev-erb α and Ror α. Western blotting was performed to assess the protein levels of BMAL1 and PER2. The results showed that apparent oscillatory expression patterns of Per2, Cry1, Rev-erb α could be observed in DPCs, whether differentiated or not. The protein level of BMAL1 was significantly increased and PER2 was decreased during odontogenic differentiation. Taken together, these findings demonstrate that circadian rhythmicity of known core clock genes exist in cultured DPCs in vitro, and the expression of genes change during differentiation process.

Impact of the photoperiod-responsive circadian clock gene period on reproductive diapause in Chrysoperla nipponensis (Okamoto).

Background: Stomach adenocarcinoma (STAD) is one of the most prevalent malignances and ranks fifth in incidence and third in cancer-related death among all malignances. The prognosis of STAD is poor. The circadian clock is regulated by interlocked transcriptional-translational feedback loops that orchestrate circadian rhythms in some biological processes, including the immune response and metabolism. However, the association between core circadian clock genes and STAD patient prognosis is unclear.Materials and Methods: In our study, bioinformatics methods were performed to explore the expression and prognostic value of core circadian clock genes in STAD and their association with immune infiltration.Results: The mRNA levels of CLOCK, CRY1 and NR1D1 were upregulated, while the mRNA levels of CRY2, PER1, PER3 and RORA were downregulated in STAD tissues compared with normal tissues. Core circadian clock genes exert promoting or inhibiting effects on certain cancer-related hallmark pathways, including the DNA damage response, cell cycle, apoptosis and RAS/MAPK pathways. Moreover, core circadian clock genes were linked to drug sensitivity or drug resistance. Prognosis analysis revealed that high expression of PER1 and NR1D1 was associated with poor overall survival, progression-free survival, and disease-free survival rates in STAD patients. Validation analysis further confirmed our result. Immune infiltration analysis demonstrated that the expression of ICOSLG and CD70 was significantly correlated with immune cells, immune biomarkers, chemokines and their receptors.Conclusions: Our results suggest that NR1D1 and PER1 are prognostic biomarkers and are associated with immune infiltration in STAD.

After completing this article, readers should be able to: 1. Describe how circadian rhythms are generated. 2. Describe how lighting influences the circadian system. 3. Delineate the period during which the origin of circadian rhythms develops. 4. Describe the relationship between maternal circadian rhythms and the development of circadian rhythms in infants. 5. Characterize the potential sequelae of impaired fetal and early neonatal circadian rhythms related to sleep patterns. 6. Describe beneficial lighting patterns for preterm infants in the neonatal intensive care nursery. Circadian rhythms are endogenously generated rhythms that have a period length of about 24 hours. Evidence gathered over the past decade indicates that the circadian timing system develops prenatally, with the suprachiasmatic nuclei (SCN) in the anterior hypothalamus, the site of a circadian clock, present by mid-gestation in primates. Recent evidence also shows that the circadian system of primate infants is responsive to light at very early stages (as early as 25 to 28 weeks’ gestation in humans) and that low-intensity lighting can regulate the developing clock. After birth, circadian system outputs mature progressively, with rhythms in sleep-wake cycles, body temperature, and hormone production generally developing between 1 and 3 months of age. The importance of light in regulation of circadian rhythm in infants is highlighted by the early establishment of rest-activity patterns that are in phase with the 24-hour light-dark cycle in preterm infants exposed to low-intensity cycled lighting. With the continued elucidation of circadian system development and influences on human physiology and illness, it is anticipated that consideration of circadian biology will become an increasingly important component of neonatal care. ### The Circadian Timing System Notable examples of circadian rhythms include the sleep-wake cycle and daily rhythms in body temperature and hormone production. Circadian rhythms are also involved in the pathogenesis of illnesses, such as reactive airway disease (eg, asthma) and myocardial infarction. The system responsible …

Environmental pollution with heavy metals is widespread, thus increasing attention has been paid to their toxic effects. Recent studies have suggested that heavy metals may influence the expression of circadian clock genes. Almost all organs and tissues exhibit circadian rhythms. The normal circadian rhythm of an organism is maintained by the central and peripheral circadian clock. Thus, circadian rhythm disorders perturb normal physiological processes. Here, we review the effects of heavy metals, including manganese, copper, cadmium, and lead, on four core circadian clock genes, i.e.,ARNTL, CLOCK, PER, and CRY genes.

A description is given of an artificial stream for studying pupation times and pupal periods of Simulium spp., of emergence traps for studying emergence times in rivers, and of a convenient arrangement for rearing batches of pupae in the laboratory.S. damnosum Theo., S. kenyae De Meillon and S. unicornutum Pomeroy pupate mainly by day, each species having a characteristic period of peak pupation.In S. damnosum and S. kenyae the time of pupation influences the pupal period, and for these and other species the pupal period is prolonged by lower temperatures. The pupal period is partly independent of these influences in so far as emergence by night is normally avoided.The timing of adult eclosion is influenced by the temperature on the day of eclosion. On warm days (midday temperature of the river 24·1–28°C) S. damnosum and other forest zone species show a peak of emergence between 06.00 and 09.00 h, while on cool days (midday temperature of the river 20·1–24°C) the peak is delayed until 09.00 to 12.00 h. On artificially cold days (refrigerator temperature 16–20°C), the peak is shifted to the late afternoon.The study of the timing of adult eclosion from pupae brought into the laboratory is complicated by the fact that the normal pattern of emergence is liable to disturbance.In the laboratory a seasonal fluctuation in the sex ratio of emerging flies occurred in S. damnosum.