Journal of Biological Rhythms最新文献

Circadian-paced biological processes are key to physiology and required for metabolic, immunologic, and cardiovascular homeostasis. Core circadian clock components are transcription factors whose half-life is precisely regulated, thereby controlling the intrinsic cellular circadian clock. Genetic disruption of molecular clock components generally leads to marked pathological events phenotypically affecting behavior and multiple aspects of physiology. Using a transcriptional signature similarity approach, we identified anti-cancer protein synthesis inhibitors as potent modulators of the cardiomyocyte molecular clock. Eukaryotic protein translation inhibitors, ranging from translation initiation (rocaglates, 4-EGI1, etc.) to ribosomal elongation inhibitors (homoharringtonine, puromycin, etc.), were found to potently ablate protein abundance of REV-ERBα, a repressive nuclear receptor and component of the molecular clock. These inhibitory effects were observed both in vitro and in vivo and could be extended to PER2, another component of the molecular clock. Taken together, our observations suggest that the activity spectrum of protein synthesis inhibitors, whose clinical use is contemplated not only in cancers but also in viral infections, must be extended to circadian rhythm disruption, with potential beneficial or iatrogenic effects upon acute or prolonged administration.

Collegiate athletes must satisfy the academic obligations common to all undergraduates, but they have the additional structural and social stressors of extensive practice time, competition schedules, and frequent travel away from their home campus. Clearly such stressors can have negative impacts on both their academic and athletic performances as well as on their health. These concerns are made more acute by recent proposals and decisions to reorganize major collegiate athletic conferences. These rearrangements will require more multi-day travel that interferes with the academic work and personal schedules of athletes. Of particular concern is additional east-west travel that results in circadian rhythm disruptions commonly called jet lag that contribute to the loss of amount as well as quality of sleep. Circadian misalignment and sleep deprivation and/or sleep disturbances have profound effects on physical and mental health and performance. We, as concerned scientists and physicians with relevant expertise, developed this white paper to raise awareness of these challenges to the wellbeing of our student-athletes and their co-travelers. We also offer practical steps to mitigate the negative consequences of collegiate travel schedules. We discuss the importance of bedtime protocols, the availability of early afternoon naps, and adherence to scheduled lighting exposure protocols before, during, and after travel, with support from wearables and apps. We call upon departments of athletics to engage with sleep and circadian experts to advise and help design tailored implementation of these mitigating practices that could contribute to the current and long-term health and wellbeing of their students and their staff members.

Newborn infants' circadian systems are not completely developed and rely on external temporal cues for synchronizing their biological rhythms to the environment. In neonatal intensive care units (NICUs), lighting is usually continuous or irregular and infants are exposed to artificial light at night, which can have negative health consequences. Therefore, the aim of this study was to evaluate the impact of the use of individual light protection equipment at night on the development and growth of preterm neonates. Infants born at less than 37 gestational weeks who no longer needed constant intensive care were admitted into a newborn nursery and randomized to either use eye masks at night (intervention, n = 21) or not (control, n = 20). Infants who used eye protection at night were discharged earlier than those in the control group (8 [5] vs 12 [3.75] days; p < 0.05). A greater variation within the day in heart rate was observed in the intervention group, with lower values of beats per minute at 1400 and 2000 h. There was no significant difference in weight gain between groups. In view of our results and of previous findings present in the literature, we suggest that combining a darkened environment at night with individual light protection devices creates better conditions for the development of preterm infants in the NICU. In addition, eye masks are an affordable and simple-to-use tool that can reduce hospitalization costs by decreasing the number of days spent in the NICU.

Developing interventions to prevent firearm-related violence and to address its consequences requires an improved understanding of when these violent events are most likely to occur. We explored gunshot events in 6 of the most populated cities in the United States by time of day, day of week, holiday/non-holiday, and month using publicly available datasets. In some of these cities, gunshot events occurred most often at nighttime, on holidays and weekends, and during summer months, with significant interaction effects. There were also time-related changes in characteristics of the victims. Primary prevention efforts aimed at curbing firearm-related violence should consider these differential risks.

Transplant studies demonstrate unequivocally that the suprachiasmatic nucleus (SCN) produces diffusible signals that can sustain circadian locomotor rhythms. There is a vascular portal pathway between the SCN and the organum vasculosum of the lamina terminalis in mouse brain. Portal pathways enable low concentrations of neurosecretions to reach specialized local targets without dilution in the systemic circulation. To explore the SCN vasculature and the capillary vessels whereby SCN neurosecretions might reach portal vessels, we investigated the blood vessels (BVs) of the core and shell SCN. The arterial supply of the SCN differs among animals, and in some animals, there are differences between the 2 sides. The rostral SCN is supplied by branches from either the superior hypophyseal artery (SHpA) or the anterior cerebral artery or the anterior communicating artery. The caudal SCN is consistently supplied by the SHpA. The rostral SCN is drained by the preoptic vein, while the caudal is drained by the basal vein, with variations in laterality of draining vessels. In addition, several key features of the core and shell SCN regions differ: Median BV diameter is significantly smaller in the shell than the core based on confocal image measurements, and a similar trend occurs in iDISCO-cleared tissue. In the cleared tissue, whole BV length density and surface area density are significantly greater in the shell than the core. Finally, capillary length density is also greater in the shell than the core. The results suggest three hypotheses: First, the distinct arterial and venous systems of the rostral and caudal SCN may contribute to the in vivo variations of metabolic and neural activities observed in SCN networks. Second, the dense capillaries of the SCN shell are well positioned to transport blood-borne signals. Finally, variations in SCN vascular supply and drainage may contribute to inter-animal differences.

Seasonal mammals register photoperiodic changes through the photoneuroendocrine system enabling them to time seasonal changes in growth, metabolism, and reproduction. To a varying extent, proximate environmental factors like ambient temperature (T_a) modulate timing of seasonal changes in physiology, conferring adaptive flexibility. While the molecular photoneuroendocrine pathway governing the seasonal responses is well defined, the mechanistic integration of nonphotoperiodic modulatory cues is poorly understood. Here, we explored the interaction between T_a and photoperiod in tundra voles, Microtus oeconomus, a boreal species in which the main impact of photoperiod is on postnatal somatic growth. We demonstrate that postweaning growth potential depends on both gestational and postweaning patterns of photoperiodic exposure, with the highest growth potential seen in voles experiencing short (8 h) gestational and long (16 h) postweaning photoperiods-corresponding to a spring growth program. Modulation by T_a was asymmetric: low T_a (10 °C) enhanced the growth potential of voles gestated on short photoperiods independent of postweaning photoperiod exposure, whereas in voles gestated on long photoperiods, showing a lower autumn-programmed growth potential, the effect of T_a was highly dependent on postweaning photoperiod. Analysis of the primary molecular elements involved in the expression of a neuroendocrine response to photoperiod, thyrotropin beta subunit (tshβ) in the pars tuberalis, somatostatin (srif) in the arcuate nucleus, and type 2/3 deiodinase (dio2/dio3) in the mediobasal hypothalamus identified dio2 as the most T_a-sensitive gene across the study, showing increased expression at higher T_a, while higher T_a reduced somatostatin expression. Contrastingly dio3 and tshβ were largely insensitive to T_a. Overall, these observations reveal a complex interplay between T_a and photoperiodic control of postnatal growth in M. oeconomus, and suggest that integration of T_a into the control of growth occurs downstream of the primary photoperiodic response cascade revealing potential adaptivity of small herbivores facing rising temperatures at high latitudes.