ArticleProceedings of the National Academy of Sciences of the United States of America2020
Wake-sleep cycles are severely disrupted by diseases affecting cytoplasmic homeostasis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 48 citations in OpenAlex.
- Resting after learning facilitates memory consolidation and reverses spatial reorientation impairments in female 3xTg-AD mice.Journal of Alzheimer's disease : JAD · 2026Article
- Post-Translational Modifications in Animal Circadian Clocks.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- How cells tame noise while maintaining ultrasensitive transcriptional responses.PLoS computational biology · 2025Article
- A Compensated Clock: Temperature and Nutritional Compensation Mechanisms Across Circadian Systems.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- PERspectives on circadian cell biology.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Review
- From homogeneity to heterogeneity: Refining stochastic simulations of gene regulation.Computational and structural biotechnology journal · 2025Article
- Phosphorylation of DNA-binding domains of CLOCK-BMAL1 complex for PER-dependent inhibition in circadian clock of mammalian cells.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Readjustment of circadian clocks by exercise intervention is a potential therapeutic target for sleep disorders: a narrative review.Physical activity and nutrition · 2024Article
- Article
- PAS Dimerization at the Nexus of the Mammalian Circadian Clock.Journal of molecular biology · 2024Review
- Coupling allows robust mammalian redox circadian rhythms despite heterogeneity and noise.Heliyon · 2024Article
- Metabolic and chemical architecture of the mammalian circadian clock.Cell chemical biology · 2023Review
- PERIOD phosphorylation leads to feedback inhibition of CK1 activity to control circadian period.Molecular cell · 2023Article
- Conformational changes in the negative arm of the circadian clock correlate with dynamic interactomes involved in post-transcriptional regulation.Cell reports · 2023Article
- Spatially coordinated collective phosphorylation filters spatiotemporal noises for precise circadian timekeeping.iScience · 2023Article
- Endogenous circadian reporters reveal functional differences ofProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Nutritional compensation of the circadian clock is a conserved process influenced by gene expression regulation and mRNA stability.PLoS biology · 2023Article
- Combined multiple transcriptional repression mechanisms generate ultrasensitivity and oscillations.Interface focus · 2022Article
- Biochemical mechanisms of period control within the mammalian circadian clock.Seminars in cell & developmental biology · 2022Review
- Systematic inference identifies a major source of heterogeneity in cell signaling dynamics: The rate-limiting step number.Science advances · 2022Article
Corrections and comments
- Commented on by
Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
The circadian clock is based on a transcriptional feedback loop with an essential time delay before feedback inhibition. Previous work has shown that PERIOD (PER) proteins generate circadian time cues through rhythmic nuclear accumulation of the inhibitor complex and subsequent interaction with the activator complex in the feedback loop. Although this temporal manifestation of the feedback inhibition is the direct consequence of PER's cytoplasmic trafficking before nuclear entry, how this spatial regulation of the pacemaker affects circadian timing has been largely unexplored. Here we show that circadian rhythms, including wake-sleep cycles, are lengthened and severely unstable if the cytoplasmic trafficking of PER is disrupted by any disease condition that leads to increased congestion in the cytoplasm. Furthermore, we found that the time delay and robustness in the circadian clock are seamlessly generated by delayed and collective phosphorylation of PER molecules, followed by synchronous nuclear entry. These results provide clear mechanistic insight into why circadian and sleep disorders arise in such clinical conditions as metabolic and neurodegenerative diseases and aging, in which the cytoplasm is congested.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.