Language：English   Publishing type：Research paper (scientific journal)  

Circadian rhythms are a universal property of organisms, and a defining property of these oscillators is the ability to maintain a precise period at different temperatures. Indeed, the discovery in the 1950s of this property, known as "temperature compensation," was a watershed event in our understanding of biological timekeeping. Since that time, however, almost no general principles have emerged that uncover the mechanistic basis of how circadian timekeepers defy the "rules" of temperature dependence of biochemical reactions. A genetic investigation of circadian temperature compensation reveals that the sensing of metabolism and ensuing modulation of the core mechanism preserves a constant circadian period. Intracellular redox sensing of metabolic rate is intrinsic to this compensation, and this relationship is conserved in bacterial and mammalian cells. These insights explain previously inexplicable observations of the interaction between redox reactions and circadian timekeeping. These results introduce a previously unknown linkage between temperature compensation and metabolism.

DOI： 10.1038/s41467-026-77031-z

PubMed

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Authorship：Corresponding author   Publishing type：Research paper (scientific journal)   Publisher：Proceedings of the National Academy of Sciences  

West-to-east transmeridian flights are more disruptive than east-to-west ones due to challenges in advancing the human circadian clock. Transient mammalian Period1 ( Per1 ) induction was predicted to predominantly advance the clock phase in our previous work. Here, we unravel a specific Per1 inducer, Mic-628, enabling abrupt phase advance in mouse behavioral rhythms, regardless of the timing of oral administration. Mic-628-treated mice re-entrain to phase-advanced light–dark cycles significantly faster. The direct interaction between Mic-628 and CRYPTOCHROME1 (CRY1) does not simply inhibit CRY1 repressor activity. Instead, the interaction facilitates the CLOCK-BMAL1 assembly, ensuring highly specific induction via a tandem E-box motif upstream of the Per1 promoter. Importantly, Mic-628-driven Per1 induction is repressed by PER1 itself. Mathematical modeling indicates that both the CRY1- and PER1-mediated transcriptional regulation fix the phase of Per1 induction irrespective of intake time, thereby predominantly advancing the clock phase. These findings underscore the potential of selective Per expression as a therapeutic approach for human circadian rhythm disorders.

DOI： 10.1073/pnas.2509943123

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Publishing type：Research paper (scientific journal)   Publisher：American Physical Society (APS)  

Notch signaling is a ubiquitous and versatile intercellular signaling system that drives collective behaviors and pattern formation in biological tissues. During embryonic development, Notch is involved in generation of collective biochemical oscillations that form the vertebrate body segments, and its failure results in embryonic defects. Notch ligands of the Delta family are key components of this collective rhythm, but it is unclear how different Delta ligands with distinct properties contribute to relaying information among cells. Motivated by the zebrafish segmentation clock, in this work we propose a theory describing interactions between biochemical oscillators, where Notch receptor is bound by both oscillatory and nonoscillatory Delta ligands. Based on previous in vitro binding studies, we first consider Notch activation by Delta dimers. This hypothesis is consistent with experimental observations in conditions of perturbed Notch signaling. Then we test an alternative hypothesis where Delta monomers directly bind and activate Notch, and show that this second model can also describe the experimental observations. We show that these two hypotheses assign different roles for a non-oscillatory ligand, as a binding partner or as a baseline signal. Finally, we discuss experiments to distinguish between the two scenarios. Broadly, this work highlights how a multiplicity of ligands may be harnessed by a signaling system to generate versatile responses.

DOI： 10.1103/7g6x-b238

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Other Link： http://harvest.aps.org/v2/journals/articles/10.1103/7g6x-b238/fulltext

Authorship：Lead author,　Corresponding author   Publishing type：Research paper (scientific journal)   Publisher：Cold Spring Harbor Laboratory  

DOI： 10.1103/PhysRevE.111.024407

Scopus

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