Evidence for ~12-h ultradian gene programs in humans

Deleted Journal, Journal Year: 2024, Volume and Issue: 1(1)

Published: Aug. 9, 2024

Mice and many marine organisms exhibit ~12-h ultradian rhythms, however, direct evidence of rhythms in humans is lacking. Here, we performed prospective, temporal transcriptome profiling peripheral white blood cells from three healthy humans. All participants independently exhibited robust transcriptional molecular programs involved RNA protein metabolism, with strong homology to circatidal gene previously identified Cnidarian species.

Language: Английский

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Preservation of ∼12-h ultradian rhythms of gene expression of mRNA and protein metabolism in the absence of canonical circadian clock

Frontiers in Physiology, Journal Year: 2023, Volume and Issue: 14

Published: May 30, 2023

Introduction: Besides the ∼24-h circadian rhythms, ∼12-h ultradian rhythms of gene expression, metabolism and behaviors exist in animals ranging from crustaceans to mammals. Three major hypotheses were proposed on origin mechanisms regulation namely, that they are not cell-autonomous controlled by a combination clock environmental cues, regulated two anti-phase transcription factors cell autonomous manner, or established oscillator. Methods: To distinguish among these possibilities, we performed post hoc analysis high temporal resolution transcriptome dataset cells lacking canonical clock. Results: In both liver BMAL1 knockout mice Drosophila S2 cells, observed robust prevalent expression enriched fundamental processes mRNA protein show large convergence with those identified wild-type liver. Bioinformatics further predicted ELF1 ATF6B as putative regulating independently fly mice. Discussion: These findings provide additional evidence support existence an evolutionarily conserved 12-h oscillator controls multiple species.

Language: Английский

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Twelve-hour ultradian rhythmic reprogramming of gene expression in the human ovary during aging

Journal of Assisted Reproduction and Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 23, 2025

Language: Английский

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Optimizing Chronotherapy in Psychiatric Care: The Impact of Circadian Rhythms on Medication Timing and Efficacy

Clocks & Sleep, Journal Year: 2024, Volume and Issue: 6(4), P. 635 - 655

Published: Nov. 5, 2024

In many medical settings, medications are typically administered in the morning or evening, aligning with patients' daily routines. This practice does not stem from chronotherapy, which involves scheduling drug administration to enhance its effectiveness, but rather way clinical operations structured. The timing of can significantly affect a medication's effectiveness and side effects, impact varying by up ten times based on circadian rhythms. Disorders such as major depression, bipolar disorder, schizophrenia linked disruptions these Recent studies have found that dysfunctions, including genetic neurohumoral changes, underlie psychiatric conditions. Issues an altered glucocorticoid rhythm due impaired HPA axis function, disturbed melatonin balance, sleep disturbances been noted psychotic disorders. Furthermore, mood disorders associated changes expression genes

Language: Английский

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Nuclear speckle rejuvenation alleviates proteinopathies at the expense of YAP1

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 21, 2024

Current treatments targeting individual protein quality control have limited efficacy in alleviating proteinopathies, highlighting the prerequisite for a common upstream druggable target capable of global proteostasis modulation. Building on our prior research establishing nuclear speckles as pivotal membrane-less organelle responsible transcriptional control, we aim to alleviate proteinopathies through speckle rejuvenation. We identified pyrvinium pamoate small-molecule rejuvenator that enhances while suppressing YAP1 signaling via decreasing surface/interfacial tension condensates interaction with intrinsically disordered region scaffold SON. In pre-clinical models, nanomolar alleviated retina degeneration and reduced tauopathy by promoting autophagy ubiquitin-proteasome system SON-dependent manner without causing cellular stress. Aberrant morphology, increased activity were also observed human tauopathies. Our study uncovers novel therapeutic targets tackling misfolding disorders within an expanded framework encompassing YAP1.

Language: Английский

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Evidence for conservation of primordial ∼12-hour ultradian gene programs in humans under free-living conditions

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: May 2, 2023

Abstract While circadian rhythms are entrained to the once daily light-dark cycle of sun, many marine organisms exhibit ∼12h ultradian corresponding twice movement tides. Although human ancestors emerged from circatidal environment millions years ago, direct evidence in humans is lacking. Here, we performed prospective, temporal transcriptome profiling peripheral white blood cells and identified robust transcriptional three healthy participants. Pathway analysis implicated RNA protein metabolism, with strong homology gene programs previously Cnidarian species. We further observed intron retention events genes involved MHC class I antigen presentation, synchronized expression mRNA splicing all Gene regulatory network inference revealed XBP1, GABP KLF transcription factor family members as potential regulators rhythms. These results suggest that biological have a primordial evolutionary origin important implications for health disease.

Language: Английский

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Reduced glucose concentration enhances ultradian rhythms in Pdcd5 promoter activity in vitro

Frontiers in Physiology, Journal Year: 2023, Volume and Issue: 14

Published: Oct. 11, 2023

Intrinsically driven ultradian rhythms in the hourly range are often co-expressed with circadian various physiological processes including metabolic such as feeding behaviour, gene expression and cellular metabolism. Several behavioural observations show that reduced energy intake or increased expenditure leads to a re-balancing of timing, favouring activity patterns when availability is limited. This suggests close link between rhythmicity homeostasis, but we currently lack models test this hypothesis at level. We therefore transduced 3T3-L1 pre-adipocyte cells reporter construct drives destabilised luciferase via Pdcd5 promotor, previously showed exhibit robust vitro . Ultradian promotor bioluminescence was observed >80% all cultures were synchronised dexamethasone, whereas significantly lower numbers exhibited non-synchronised (∼11%). Cosine fits cultured measured low glucose concentrations (2 mM 5 mM), higher amplitudes than other cultures, shorter period (6.9 h vs. 8.2 h, N = 12). Our findings substantial which clocks have been , line synchronisation rhythms. Critically, amplitude enhanced conditions, suggesting enhances level

Language: Английский

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Preservation of ∼12-hour ultradian rhythms of gene expression of mRNA and protein metabolism in the absence of canonical circadian clock

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: May 2, 2023

Abstract Besides the ∼24-hour circadian rhythms, ∼12-hour ultradian rhythms of gene expression, metabolism and behaviors exist in animals ranging from crustaceans to mammals. Three major hypotheses were proposed on origin mechanisms regulation namely that they are not cell-autonomous controlled by a combination clock environmental cues, regulated two anti-phase transcriptional factors manner, or established oscillator. To distinguish among these possibilities, we performed post-hoc analysis high temporal resolution transcriptome dataset cells lacking canonical clock. In both liver BMAL1 knockout mice Drosophila S2 cells, observed robust prevalent expression enriched fundamental processes mRNA protein show large convergence with those identified wild-type liver. Bioinformatics further predicted ELF1 ATF6B as putative transcription regulating independently fly mice. These findings provide additional evidence support existence an evolutionarily conserved 12-hour oscillator controls multiple species.

Language: Английский

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Basic research and opportunities for translational advancement in the field of mammalian ∼12-hour ultradian chronobiology

Frontiers in Physiology, Journal Year: 2024, Volume and Issue: 15

Published: Nov. 20, 2024

Repetitive variations, such as oscillation, are ubiquitous in biology. In this mini review, we present a general summary of the ∼24 h circadian clock and provide fundamental overview another biological timekeeper that maintains ∼12 oscillations. This oscillator is proposed to function independently regulate ultradian rhythms relevant both protein homeostasis liver health. Recent studies exploring these humans discussed, followed by our proposal mammary gland physiology represents promising area for further research. We conclude highlighting potential translational applications chronobiology.

Language: Английский

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Epigenetic regulation of global proteostasis dynamics by RBBP5 ensures mammalian organismal health

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 13, 2024

Proteostasis is vital for cellular health, with disruptions leading to pathologies including aging, neurodegeneration and metabolic disorders. Traditionally, proteotoxic stress responses were studied as acute reactions various noxious factors; however, recent evidence reveals that many proteostasis stress-response genes exhibit ∼12-hour ultradian rhythms under physiological conditions in mammals. These rhythms, driven by an XBP1s-dependent 12h oscillator, are crucial managing proteostasis. By exploring the chromatin landscape of murine hepatic we identified RBBP5, a key subunit COMPASS complex writing H3K4me3, essential epigenetic regulator RBBP5 indispensable regulating both oscillator transcriptional response stress, acting co-activator transcription factor XBP1s. ablation leads increased sensitivity chronic inflammation, steatosis mice, along impaired autophagy reduced cell survival

Language: Английский

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