bims-ciryme 2026-04-26 papers

Plant Physiol. 2026 Apr 22. pii: kiag235. [Epub ahead of print]

XAP5 CIRCADIAN TIMEKEEPER coordinates circadian rhythms and anthocyanin biosynthesis independently of splicing.

Circadian clocks provide plants with an adaptive advantage by enabling them to anticipate daily environmental changes. The periodicity of circadian clocks is regulated at multiple levels of gene expression, including transcription, mRNA processing, translation, and protein modification. Numerous mRNA splicing factors have been implicated in maintaining circadian period length. However, these factors often play additional roles in transcription, making it difficult to determine whether they affect the clock through splicing-dependent or -independent mechanisms. We and others have shown that XAP5 CIRCADIAN TIMEKEEPER (XCT) and components of the PRE-MRNA-PROCESSING FACTOR 19 (PRP19) complex, including the functionally redundant PRP19A and PRP19B, physically associate and regulate both splicing and circadian rhythms. Here, our transcriptome analyses reveal that the antagonistic regulation of circadian period length by XCT and PRP19 likely occurs through splicing-independent mechanisms. Interestingly, both factors co-regulate expression of a substantial set of shared target genes involved in RNA metabolism, photosynthesis, and stress responses despite having largely distinct targets for splicing. Gene co-expression analysis followed by functional characterization identified anthocyanin biosynthesis as another process antagonistically regulated by XCT and PRP19. Nonetheless, we found genetic perturbation of anthocyanin production does not affect circadian period, suggesting that the observed correlation between anthocyanin levels and circadian period may instead reflect disruption of a shared upstream regulatory pathway. Together, our findings suggest involvement of XCT and PRP19 in the transcriptional coordination of anthocyanin biosynthesis and biological timing, expanding their known roles beyond mRNA splicing.

DOI: https://doi.org/10.1093/plphys/kiag235

Diabetologia. 2026 Apr 24.

Bmal1 overexpression in suprachiasmatic nucleus protects from retinal neurovascular deficits in a mouse model of diabetes.

Neha Mahajan, Qianyi Luo, Jodi Lukkes, Surabhi D Abhyankar, Ashay D Bhatwadekar.

AIMS/HYPOTHESIS: The suprachiasmatic nucleus regulates circadian rhythms and influences physiological and behavioural functions. Clock genes not only play a critical role in orchestrating circadian rhythms, but also regulate a variety of bodily functions. While Bmal1, a clock gene, is vital for maintaining optimal circadian rhythms, its therapeutic potential in type 2 diabetes remains unexplored.
METHODS: In this study, db/db mice, a well-established model of type 2 diabetes exhibiting arrhythmic behaviour and complications, were injected stereotaxically with AAV-Bmal1 or a control virus into the suprachiasmatic nucleus to evaluate the protective effects of Bmal1 overexpression on neurovascular deficits of type 2 diabetes. Given the complex neurovascular network and the eye's unique accessibility as a transparent system, ocular complications were selected as a model to examine the neuronal functional, behavioural and vascular benefits of central overexpression of Bmal1.
RESULTS: Bmal1 overexpression decreased the free-running period, which otherwise is lengthened in db/db mice. Retinal neuronal function was restored on the electroretinogram, along with optomotor behaviour and visual acuity enhancements. Retinal vascular deficits were also significantly reduced. Notably, Bmal1 overexpression decreased fat content in genetically predisposed obese db/db mice compared with the untreated db/db group. As the suprachiasmatic nucleus is known to regulate hepatic glucose production via sympathetic mechanisms, glycaemic control and pyruvate tolerance tests were evaluated. Glucose homeostasis was improved in Bmal1-overexpressing mice, accompanied by a significant reduction in hepatic gluconeogenesis. Plasma noradrenaline (norepinephrine) and liver tyrosine hydroxylase levels were reduced, indicating a protective regulation of adrenergic signalling.
CONCLUSIONS/INTERPRETATION: Our study highlights the therapeutic potential of central overexpression of a clock gene, Bmal1, to mitigate metabolic and neurovascular deficits of type 2 diabetes, offering a compelling framework for incorporating circadian rhythms into managing diabetes and its complications.

Keywords: Bmal1 ; Circadian clock; Diabetic retinopathy; Gluconeogenesis; Glucose metabolism; Noradrenaline; Retinal deficits; Type 2 diabetes

DOI: https://doi.org/10.1007/s00125-026-06734-1

NPJ Digit Med. 2026 Apr 21.

Quantifying sleep wake rhythms in the hospital environment with digital technologies.

Postoperative clinical care is prone to circadian desynchronization that may influence health outcomes. In an exploratory, feasibility-oriented and signal-exploration effort, we collected 1.8 million data points using 11 remote sensors during preoperative, in-hospital and post-discharge settings in 13 elective cardiac surgery patients (5.2% enrolled from 252 screened). We found that room traffic continued during nighttime with ≥1 visit/h. Sound levels exceeded the recommended 45 dBA threshold (51.9 ± 3.3 vs. 48.3 ± 4.2 dBA during nighttime). Brightness dropped at night (89.9 ± 87.7 to 3.7 ± 9.8 lux), but bright light exposures occurred. Ambient room temperature lacked sleep-inducing diurnal variability. Behavioral-physiological rhythms were disrupted and phase-shifted during hospitalization. Time awake during night hours increased from 10.7 ± 7.9% preoperatively to 34.8 ± 29.1% in-hospital. Cognitive function scores decreased (26.8 ± 2.8 points preoperatively to 24.7 ± 3.9 points in-hospital) with 31% of patients developing transient mild impairment. These data will inform the design of a controlled trial seeking to modify circadian/diurnal disruptors to enhance patient outcomes. Clinicaltrials.gov NCT05828680, November 21, 2022.

DOI: https://doi.org/10.1038/s41746-026-02639-w