bims-ciryme 2026-04-05 papers

J Cyst Fibros. 2026 Mar 31. pii: S1569-1993(26)00087-1. [Epub ahead of print]

Altered responsiveness to photic stimuli contribute to circadian disruption in cystic fibrosis.

Danica F Patton-Parfyonov, Eden N Kenner, Deborah A Corey, Thomas J Kelley, Rebecca Darrah.

BACKGROUND: People with cystic fibrosis (pwCF) and animal models show evidence of disrupted circadian rhythms (CR). CRs are controlled by light sensitive neurons of the suprachiasmatic nucleus (SCN). Characterizing how the CF SCN responds to light will inform mechanisms behind CR disruption and help to inform CR based treatments to mitigate CF symptoms exacerbated by circadian disruption.
METHODS: Mice were entrained and subsequently exposed to a 30 min light pulse one hour after usual lights out. The magnitude of the resulting phase delay in subsequent activity onset and molecular correlates of photic input at the SCN were then compared between CF and WT mice.
RESULTS: Light induced phase delays of activity onset in CF mice were reduced compared to WT controls. Reduced behavioral responses were also associated with altered molecular responses in the SCN, including attenuated cFOS levels in CF vs WT SCN. Data show that phosphorylation of ribosomal protein 6 (pS6) is reduced in CF, while targets down stream of 4E-BP1 such as vasoactive intestinal polypeptide levels (VIP) appear the same between genotypes.
CONCLUSIONS: Behavioral and molecular responses to a light pulse differ between CF and WT mice. Together these data suggest that similar photic input from the retina is being received by the SCN of CF and WT mice, but the mounted intracellular response to that photic input differs in CF. Investigation into these differences will be integral to understanding circadian disruption in CF and informing future intervention for CF symptoms known to be exacerbated by circadian disruption.

Keywords: Circadian rhythms; Cystic fibrosis; Suprachiasmatic nucleus

DOI: https://doi.org/10.1016/j.jcf.2026.03.020

Nat Rev Drug Discov. 2026 Apr 02.

Dialling up the circadian clock to target ageing.

M Teresa Villanueva.

Keywords: Ageing; Brain; Drug discovery

DOI: https://doi.org/10.1038/d41573-026-00057-x

bioRxiv. 2026 Mar 24. pii: 2026.03.21.713346. [Epub ahead of print]

Metaplastic sleep regulation in Drosophila determined by microscale circadian neural dynamics.

Anelise N Hutson, Alexa N Zarjetskiy, Yutian J Zhang, Natalia Pokaleva, Elizabeth M Paul, Yizhou Xie, Bryan Chong, Victor M Sanchez Franco, Lauren H Zukowski, Eileen E Faulk, Joel A Walker, Ayanna M Brown, Dieu Linh Nguyen, Faith S Ferry, Eleanora M Snyder, Masashi Tabuchi.

The biophysical mechanisms by which circadian clock neurons integrate temporal coding signals to regulate sleep remain elusive. Here, using Drosophila , we identify Rabphilin (Rph) in DN1p clock neurons as a key stabilizer of the metaplasticity setpoint governing circadian regulation of sleep. Rph protein levels are elevated at night relative to daytime and modulate stochastic process of DN1p membrane potential dynamics linked to variability in synaptic activity at connections between DN1p neurons and their downstream postsynaptic partners. We find that Rph acts as a bidirectional regulator of synaptic plasticity thresholds. Under dim nocturnal light stimulation, Rph knockdown permits synaptic potentiation, whereas synthesized Rph introduction induces synaptic depression. In contrast, under optogenetic manipulation mimicking daytime spiking in DN1p neurons, these effects are reversed. We further show that spike-timing-dependent plasticity emerges when postsynaptic spiking is engaged, with nocturnal dim light conditions determining the direction of plasticity. Together, these findings establish a mechanistic link between microscale circadian neural dynamics and hierarchical metaplastic regulation, demonstrating how circadian regulation of sleep dynamically balances stability and adaptive flexibility through circadian setpoints and environmental nocturnal light interactions.
Significance Statement: We show that circadian metaplasticity regulates sleep through membrane potential dynamics. Circadian clock neurons implement flexible metaplasticity, whereby the direction can be determined by internal circadian setpoints and interactions with nocturnal environmental light. This mechanism engages spike-timing-dependent plasticity to determine plasticity polarity. Our findings identify membrane potential dynamics as a computational substrate for physiological state control, linking molecular mechanisms to circuit-level circadian regulation of sleep. Together, they reframe sleep regulation as an active metaplastic process that hierarchically integrates microscale circadian neural dynamics to optimize circuit function.

DOI: https://doi.org/10.64898/2026.03.21.713346

Proc Biol Sci. 2026 Apr 01. pii: 20252728. [Epub ahead of print]293(2068):

Awake and hungry: artificial light at night disrupts behaviour and reproductive ecology in a wild migratory bird.

Juliette Champenois, Sayuri Diaz-Palma, Irene Di Lecce, Mariusz Cichoń, Lars Gustafsson, Joanna Sudyka.

Artificial light at night (ALAN) disrupts biological rhythms across taxa, yet behavioural mechanisms linking exposure to population consequences remain poorly understood. Long-distance migrants encounter ALAN across their annual cycle but remain understudied despite experiencing stronger performance impacts than sedentary species. We experimentally introduced ALAN into nest-boxes of a migratory passerine, the collared flycatcher (Ficedula albicollis), breeding in Gotland, Sweden. Nestlings were exposed to ALAN from 2 days post-hatching until fledging, and we video-recorded parental and nestling activity over 24 h on day 8 post-hatching. Across a high-resolution behavioural dataset (32 100 nestling and 3709 parental events), ALAN-exposed nestlings begged more frequently and for longer at night compared with dark controls, revealing disrupted circadian activity. These effects cascaded to parents: both females and males began feeding earlier and ceased later, while reducing hourly feeding rates relative to controls. Consequently, ALAN nestlings fledged at older ages, consistent with delayed development, though reproductive success (number of fledged offspring) was unaffected. Our study provides clear empirical support for socially mediated behavioural mechanisms whereby both parents respond to ALAN, disrupting family level coordination, developmental trajectories and parental investment. This temporal destabilization of social synchrony uncovers a novel ecological pathway through which anthropogenic light alters behavioural timekeeping and life-history trajectories in the wild.

Keywords: ALAN; activity offset; activity onset; begging behaviour; circadian rhythms; light pollution; migratory birds; parental care; urbanization

DOI: https://doi.org/10.1098/rspb.2025.2728

Saf Health Work. 2026 Mar;17(1): 70-75

Do the Long-Term Cardiometabolic Effects of Night Shift Work Differ Between Men and Women? A 17-Year Cohort Study of the U.S. Workforce.

María Romero-Parra, Óscar Caballero, Antonio García-Hermoso, José Francisco López-Gil, Jacqueline Páez-Herrera, Rodrigo Yáñez-Sepúlveda, Yasmin Ezzatvar.

Background: Shift work, particularly in night shifts, has been linked to adverse health outcomes, including disruptions in circadian rhythms that may contribute to metabolic disorders. However, sex-related differences in the impact of night shift work on cardiometabolic health remain understudied. This study sought to examine the relationship between night shift work and cardiometabolic health in young adults, identifying potential sex-related differences.
Methods: In this prospective cohort study, a total of 3201 participants (mean age: 22.08 years, 59.9% women) were analyzed over a 17-year period. Relative risks (RRs) with 95% confidence intervals (CIs) were calculated to evaluate the impact of night shift work on cardiometabolic health outcomes, including obesity, hyperlipidemia, hypertension, type 2 diabetes, and metabolic syndrome (MetS).
Results: At Wave V, 74.7% of participants were diagnosed with overweight/obesity, 51.8% with abdominal obesity, 15.5% with hyperlipidemia, 29.1% with hypertension, 8.3% with type 2 diabetes, and 20.9% with MetS. Night shift work was associated with an increased risk of obesity and abdominal obesity in women (RR = 1.99, 95% CI: 1.08 to 3.65 and RR = 1.60, 95% CI: 1.07 to 2.56, respectively) but not in men. Women also showed an elevated risk of diabetes (RR = 2.69, 95% CI: 1.49 to 4.86), whereas no significant relationship was identified in men. Night shift work was not significantly associated with hypertension and MetS in either men or women.
Conclusion: Women working night shifts may benefit from targeted interventions for cardiometabolic health, particularly in managing weight and preventing diabetes, while men did not exhibit similar associations.

Keywords: Diabetes; Obesity; Shift work; Workforce

DOI: https://doi.org/10.1016/j.shaw.2025.11.001

bioRxiv. 2026 Mar 25. pii: 2026.03.23.713759. [Epub ahead of print]

Single-cell Transcriptomic Variance Analysis Reveals Intercellular Circadian Desynchrony in the Alzheimer's Affected Human Brain.

Henry C Hollis, Anthony Veltri, Ksenija Korac, Vilas Menon, David A Bennett, Sean M Ronnekleiv-Kelly, Junhyong Kim, Ron C Anafi.

Bulk tissue rhythms arise from the coordination of thousands of individual cellular oscillations. Bulk rhythm amplitude differences may reflect changes in the amplitude of the underlying cellular oscillators or changes in their temporal coherence. To resolve this fundamental ambiguity, we developed ORPHEUS ( O scillatory R hythm P hase H eterogeneity E stimated U sing S tatistical-moments), an analytical method that quantifies cellular desynchrony by leveraging the unique 12hr rhythmic signature it imparts on intercellular expression variance. After validating ORPHEUS in silico and on data from the mouse suprachiasmatic nucleus (SCN), we applied it to data from the mouse liver and human brain to uncover disease- and pathway-related differences in intercellular synchrony. In both tissues, we found that circadian synchrony is higher in cells and samples with higher MTORC activity. Most critically, we observed a dramatic loss of cellular synchrony in excitatory neurons from subjects with Alzheimer's Disease (AD) dementia. By decoupling the influence of cellular amplitude and synchrony, ORPHEUS introduces a new, interpretable tool for analyzing circadian coordination in time-course single-cell data.

DOI: https://doi.org/10.64898/2026.03.23.713759