npj Biological Timing and Sleep最新文献

This review discusses how temperature signals are integrated into the Arabidopsis circadian clock and proposes Temperature-Dependent Alternative Splicing (TDAS) of core clock genes as an additional mechanism to adapt the circadian system to temperature changes. We present examples of TDAS in a range of organisms, pointing towards a conserved mechanism that enables temperature adaptation.

Cerebrospinal fluid (CSF) exchanges with the central nervous system's immediate environment and interfaces with systemic circulation at the blood-CSF barrier. CSF composition reflects brain states, contributes to brain health and disease, is modulated by circadian rhythms and behaviors, and turns over multiple times per day, enabling rapid signal relay. Mechanisms of how CSF elements change over circadian time and influence function can be harnessed for diagnostic biomarkers and therapeutic intervention.

Cardiometabolic disease is a leading cause of death worldwide. One factor that may contribute to the risk, onset, and severity of symptoms is disrupted circadian rhythms. Our study uses two strains of mice to further elucidate this relationship: healthy controls, and a mouse model of insulin resistance with short freerunning periods (~ 22.75 h) and enlarged hearts, raised in either a 24-h or 22.75-h LD cycle. Through glucose and insulin tolerance tests, routine electrocardiograms from one to four months old, and histology, we reveal worse cardiometabolic health outcomes for mice gestated and housed in a mismatched LD cycle compared to those in an LD cycle that matches their endogenous rhythm. This was characterized by heightened blood glucose levels following a glucose or insulin bolus, altered electrophysiological parameters of the cardiac waveform, and increased cardiomyocyte size. Circadian disruption due to work/social schedules or circadian-related disorders in people is often confounded with other unhealthy lifestyles. The present study demonstrates that circadian disruption on its own can lead to adverse health states.

We examine the relationship between sleep, glymphatics and Alzheimer's disease (AD), and recent work questioning glymphatic clearance during sleep. We highlight a need for understanding glymphatic and/or other mechanism of clearance during sleep, and review glymphatic flow measurement methods. Further, we explore dual orexin receptor antagonists (DORAs) potential to mitigate AD sleep disturbances and enhance clearance. Further research could elucidate a linkage between DORAs, improved sleep and reducing AD pathophysiology.

Parasites harm host fitness and are pervasive agents of natural selection capable of driving the evolution of host resistance traits. Previously we demonstrated evolutionary responses to artificial selection for increasing behavioral immunity to Gamasodes queenslandicus mites for Drosophila melanogaster. Here, we report transcriptional shifts in metabolic processes due to selection for mite resistance. We also show decreased starvation resistance and increased use of nutrient reserves in flies from mite-resistant lines. Resistant lines exhibited increased activity, reduced sleep, and elevated oxygen consumption during the night. Using a panel of D. melanogaster lines exhibiting variable sleep durations, we found a positive correlation between mite resistance and reduced sleep. Restraining the activity of artificially selected mite-resistant flies during exposure to parasites reduced their resistance advantage relative to control flies. The results suggest that ectoparasite resistance in this system involves increased activity during the scotophase and metabolic gene expression at the expense of starvation resistance.

This review summarizes recent advances in understanding the cyanobacterial circadian clock, emphasizing how the KaiA, KaiB, and KaiC proteins generate robust, temperature-compensated rhythms through ordered phosphorylation, conformational switching, and dynamic protein interactions. A comparative analysis of 30 KaiC structures under different states of phosphorylation and nucleotide binding is also presented. Together, these structural and mechanistic insights illuminate fundamental principles of biological timekeeping and evolutionary adaptations in these photosynthetic prokaryotes.

Both parasite manipulation of host behavior and the roles of circadian clocks in infectious disease are not well understood. However, studies into parasite-manipulated insects suggest that host rhythms are altered at different levels of biological organization. Here, we discuss this hypothesis in the context of circadian plasticity. We argue that striking overlap between manipulation mechanisms and plastic functioning of the insect clock exists across independently evolved parasite-host systems. As such, investigating parasitic behavioral manipulation provides an opportunity to better understand circadian plasticity and how infection and clocks intersect across taxa.

The retinal photopigment melanopsin is also expressed in subcutaneous white adipose tissue (scWAT). Through melanopsin, light can modulate scWAT metabolism, but its impact on circadian phase is unclear. In vitro exposure of murine scWAT to bright light at different times over 24 h did not elicit phase shifts, unlike the response to corticosterone. This finding suggests that the direct impact of bright light on scWAT metabolism occurs in a circadian-independent manner.

Time-of-day variation in the molecular profile of biofluids and tissues is a well-described phenomenon, but-especially for proteomics-is rarely considered in terms of the challenges this presents to reproducible biomarker identification. We provide a case study analysis of human circadian and ultradian rhythmicity in proteins, including in the complement and coagulation cascades and apolipoproteins, with PLG, CFAH, ZA2G and ITIH2 demonstrated as rhythmic for the first time. We also show that rhythmicity increases the risk of Type II errors due to the reduction in statistical power from increased variance, and that controlling for rhythmic time-of-day variation improves statistical power and reduces the chances of Type II errors. We recommend that best practice in proteomics study design should account for temporal variation and that time of sampling be reported as part of study metadata. These simple steps can mitigate against both false and missed discoveries, as well as improving reproducibility.

Air pollution is a ubiquitous neurotoxicant linked to altered structural brain connectivity. Sleep may offer neuroprotection through its roles in brain waste clearance and immune regulation. Using Fitbit-derived sleep data and multi-shell diffusion MRI from 2178 children (ages 10-13) in the ABCD Study®, we examined whether sleep moderated associations between prenatal and childhood exposure to PM_2.5, NO₂, and O₃ and white matter microstructure. Restriction spectrum imaging yielded restricted normalized isotropic (RNI) and directional (RND) metrics, averaged across tracts. Pollution exposure was estimated at prenatal and childhood (ages 9-10) residences. Linear mixed-effects models tested sleep-by-pollution interactions on RNI/RND. Childhood NO₂ and prenatal O₃ interacted with sleep duration and efficiency, respectively, to influence RND. Among children with similar pollutant exposure, those with longer sleep duration and higher sleep efficiency had lower RND than peers with poorer sleep. This suggests that healthy sleep may buffer adverse effects of air pollution on white matter integrity.