bims-ciryme 2026-09-06 papers

Nat Commun. 2026 Aug 06. pii: 9438. [Epub ahead of print]17(1):

Chrono-atlas of cell-type specific daily gene expression rhythms in the regenerating colon.

Vania Carmona-Alcocer, Cédric Gobet, Jessie MacDonald, Zainab Taleb, Felix Naef, Phillip Karpowicz.

The circadian clock is present throughout the body, including the intestine, where it regulates daily physiology through rhythmic gene expression. The large intestine (colon) is composed of many functionally distinct cell types; how daily rhythms in transcript abundance are coordinated in specific cells is not known. Using single-cell transcriptomics, we analyzed 24-hour gene expression rhythms in all major cell types of the colon following injury. Such rhythms are not uniformly distributed: rhythmic genes, including circadian clock components, clock targets, and systemic response programs, differ in their timing, and are cell-type-, region-, or injury- specific. Compared to stromal and muscle cells, which exhibit robust circadian clock rhythms, epithelial cells show weaker oscillations. During regeneration, cells of the epithelium, stroma, and immune system display strong biphasic rhythms in metabolic, protein processing, and temperature response genes, and epithelial clocks are reprogrammed to become 12-hours antiphasic in timing. Our data reveal unexpected complexity in the colon and provide a resource by identifying the cellular source of 24-hour transcript rhythms.

DOI: https://doi.org/10.1038/s41467-026-76318-5

Sci Rep. 2026 09 02. pii: 27497. [Epub ahead of print]16(1):

CaMKIIα mediates feedback effects of wheel-running activity on the circadian pacemaker in mice.

Tomoko Yoshikawa, Ken-Ichi Honma, Isao Tokuda, Sato Honma.

CaMKIIα functional knockout mouse (K42R) showed substantial changes in the entrainment pattern of running-wheel (RW) rhythm to a short (LD6:18) but not to a long (LD18:6) photoperiod. In wild type mice (WT), entrainment to LD6:18 occurred at the light-off phase, whereas in most K42R entrainment took place at the light-on phase. These differences are well explained by lengthening of circadian period (τ) and compromising the couplings between the activity-onset and -end in K42R. Indeed, τ in K42R and WT were longer and shorter than 24 h, respectively, under the following constant darkness (DD). Without RW τ was lengthened in WT, whereas it was shortened in K42R. Similarly, activity time was lengthened in WT but shortened in K42R. Importantly, τ without RW was not different between the two genotypes, which were confirmed in naive mice. Tau and α returned to the pre-removal levels after RW re-introduction in both WT and K42R. These results indicate that the changes of behavioral rhythm in K42R are due to a lack of feedback effects of RW activity, which are mediated by CaMKIIα-dependent mechanisms. A two-oscillator model assuming involvement of CaMKIIα in the coupling between them successfully simulated the effects of RW activity in K42R.

Keywords: Activity time; CaMKIIα; Circadian period; Entrainment; Oscillatory coupling; Photoperiod

DOI: https://doi.org/10.1038/s41598-026-54563-4

Nat Commun. 2026 Sep 03. pii: 9139. [Epub ahead of print]17(1):

Functional coupling between MC4R and Kir7.1 contributes to clozapine-induced weight gain in female mice.

Li Li, Ciria C Hernandez, Luis E Gimenez, Baijie Xu, Naima S Dahir, Alys Peisley, Zan Wu, Meilin Chen, Alexandra Serrato, Rong Wan, Swati, Shari G Birnbaum, Roger D Cone, Chen Liu.

Most antipsychotic drugs (APDs) cause hyperphagia and weight gain, yet the neural mechanisms underlying these metabolic side effects remain elusive, in part due to difficulties in modeling them in rodents. Here, we establish a mouse model that recapitulates clozapine-induced metabolic syndrome, enabling mechanistic investigation of this widely prescribed APD. We show that clozapine promotes obesity in female mice by driving hyperphagia, which requires functional coupling between the melanocortin 4 receptor (MC4R) and the Kir7.1 potassium channel. Within the broader context of clozapine's polypharmacology, this signaling axis emerges as a critical downstream convergence node for APD-induced metabolic dysfunction. Mechanistically, clozapine inhibits MC4R-expressing neurons in the paraventricular nucleus of the hypothalamus by enhancing MC4R-Kir7.1 coupling, thereby increasing inward potassium currents. Notably, clozapine produces this inhibition without binding the MC4R orthosteric site and without engaging canonical Gαs signaling. Genetic deletion of Kir7.1 in MC4R neurons or pharmacological inhibition of Kir7.1 reverses clozapine-induced weight gain while preserving its behavioral efficacy in established antipsychotic assays. Together, these findings reveal a G-protein-independent mechanism by which clozapine disrupts energy balance and identify MC4R-Kir7.1 coupling as a therapeutically tractable pathway for mitigating APD-associated metabolic dysfunction.

DOI: https://doi.org/10.1038/s41467-026-76561-w

Bioinform Adv. 2026 ;6(1): vbag226

TimeTraits: extracting functional traits from biological time-series in R.

Sarah C L Lock, Marina I Knight, Seth J Davis, Daphne Ezer.

Motivation: It is currently challenging for scientists to extract meaningful parameters from circadian rhythms that dynamically change over time (i.e. non-stationary rhythms). Circadian rhythms may be non-stationary due to dynamic conditions, such as changes in photoperiod. Circadian rhythms are also nonstationary when plants are suddenly placed under continuous light conditions after a period of entrainment, as their clocks slowly drift without external entrainment signals.
Results: TimeTraits provides a series of functions to enable the extraction of parameters from time series data using Functional Data Analysis methods. We demonstrate its utility in dissecting the changes in curve shape of a circadian clock bioluminescence marker, following a photoperiod shift in wildtype and phyB Arabidopsis.
Availability and implementation: TimeTraits is available in CRAN: https://cran.r-project.org/web/packages/TimeTraits.

DOI: https://doi.org/10.1093/bioadv/vbag226