Chronotype reflects an individual's preferred timing of sleep/daily activities and is typically regarded as a stable trait, though it varies across the lifespan and may fluctuate also over shorter periods of time. Here, we investigate the temporal stability of self-assessed chronotype and its modulation by behavioral advice in a large cohort of University students participating in a 2-arm circadian hygiene education initiative (either encouraging consistency or advancement of sleep, meals, and exercise timing). Students provided demographic and sleep quality information, and repeated chronotype assessments (2-22 months) using the Self-Morningness/Eveningness (Self-ME) question, which offers a choice among 4 categories (definitely morning, morning, evening, definitely evening) and the Ultrashort Munich ChronoType Questionnaire (μMCTQ), which has midsleep and social jetlag as outcomes. Two main samples were analyzed: students completing baseline/2-month follow-up assessments (n = 1902) and students completing baseline/one later assessment, at any time (n = 2820); a subgroup with 3 available assessments (n = 1257) was also examined. Agreement between subsequent Self-ME assessments was good in all samples (0.6 < Cohen's k < 0.8), with approximately 70% of students confirming their first assessment at 2 months, with variations (62%-73%) depending on time between assessments and behavioral advice; transitions mostly occurred between adjacent Self-ME categories. Nonetheless, approximately 30% of participants changed category between 2 assessments, and those who moved once were more likely to move again. "Non movers" exhibited more extreme sleep-wake habits. Furthermore, midsleep and social jetlag changed over the calendar year in ways that seemed to reflect the time-course/constraints of the academic year. The 2 circadian hygiene interventions influenced chronotype stability slightly and differently, particularly in morning types, who probably found it easier to comply with the suggestion of advancing sleep-wake timing. In conclusion, chronotype in young adults shows relative stability but is plastic within limits, also in relation to the way it is measured.

Dysregulation of the serotonergic system is consistently noted in cases of psychiatric pathology. Circadian rhythm dysregulation is also a common comorbidity in psychiatric populations, and the circadian and serotonergic systems have a long history of coregulation. Despite this, it is not yet known whether serotonergic neurons house circadian molecular clocks, the transcription and translation feedback loops that drive circadian rhythms at the cellular level. To investigate this, brain tissue was extracted from adult male rats every 4 h throughout the light-dark cycle. Radiolabeled in situ hybridization was used to quantify clock gene expression in the dorsal and median raphe, the two nuclei responsible for providing the majority of serotonin to the brain. We discovered oscillatory rhythms in the expression of clock genes Bmal1, Per1, and Per2 with a period of approximately 24 h, and confirmed via fluorescent in situ hybridization that serotonergic (positive for Tph2, the rate-limiting enzyme in serotonin synthesis) neurons do express clock genes. The roughly antiphasic relationship between Bmal1 and the Per genes supports the existence of a circadian molecular clock in these cells. We next measured clock gene expression in neighboring brainstem regions that were not serotonergic, and found that although they all had similar daily clock gene expression profiles, the dorsal and median raphe had higher amplitude Bmal1 expression, and trending higher amplitude Per1 expression. This study adds to the growing list of extra-SCN (suprachiasmatic nucleus) molecular clocks reported in the brain. The prevalence of this circadian machinery, especially in regions of the brain so relevant to psychiatric health, underscores the importance of circadian rhythms to well-being. A greater understanding of the unique nature of circadian rhythms in discrete brain regions is a fruitful frontier for improving psychiatric treatment outcomes and overall health.

In adult samples, tightly-controlled laboratory studies indicate the presence of circadian rhythms in positive (and negative) affect. Naturalistic studies also suggest the presence of diurnal positive affect rhythms in adults, the characteristics (acrophase, mesor, and amplitude) of which vary by self-report circadian preference-greater evening preference is associated with later acrophase, lower mesor, and lower amplitude in positive affect. We examined the extent to which diurnal affect rhythms are associated with 4 different measures of circadian timing, including dim light melatonin onset, in a sample of high-school adolescents who reported at least one drink of alcohol in their lifetime (N = 126, 17.3 ± 0.87 years, 55.6% female). Cosinor models found support for robust diurnal rhythms in positive, but not negative, affect. The overall modeled positive affect rhythm had an acrophase at 3:39 PM, a mesor of 9.77, and an amplitude of 1.61. Later circadian timing was associated with later acrophase in positive affect rhythms across the following measures: circadian preference (3:00 PM vs 4:20 PM, p < .001), chronotype (3:20 PM vs 4:11 PM, p = .014), and actigraphy-based midsleep (3:08 PM vs 4:16 PM, p = .014). We did not find significant associations between circadian phase (dim light melatonin onset) and positive affect rhythms. We also explored weekday-weekend differences in positive affect rhythms, finding significantly higher mesor (9.71 vs 9.99, p = .004) and lower amplitude (1.69 vs 1.26, p = .008) on the weekends than weekdays. In sum, compared to their peers, adolescents with later sleep and circadian timing experience a delayed peak in positive affect during the day, which may have consequences for behavioral activation and depressed mood. These findings underscore the importance of considering the role of sleep and circadian factors in affective processes during adolescence.

This review summarizes recent insights into the roles of the circadian clock in regulating cancer hallmarks, with a focus on its impact on the tumor microenvironment, and highlights the translational promise of circadian-informed strategies for cancer therapy. The circadian clock is a 24-hour biological timekeeping system that aligns physiological processes with cyclic environmental cues, such as light-dark cycles. Disruptions of circadian rhythms caused by lifestyle factors, including shift work, irregular sleep patterns, and jet lag, can lead to physiological dysregulation and increased risk of various diseases including cancer, positioning the circadian clock as both a critical driver of tumorigenesis and a potential target for chronotherapies. This review provides a comprehensive overview of circadian regulation in tumorigenesis across diverse cancer types by framing its role according to established cancer hallmarks, with particular emphasis on how the circadian system shapes immune cell dynamics within the tumor microenvironment to modulate tumor progression and immune surveillance. We further discuss recent preclinical and clinical advances in chronotherapy, highlighting how aligning therapeutic interventions with biological rhythms can enhance treatment efficacy, including responses to immunotherapy. By integrating mechanistic insights with translational applications, this review bridges circadian biology and oncology, providing a framework for future chronobiology-based cancer therapies.

On 6 January 2025, the field of chronobiology lost a pioneer in Sue Ann Lingenfelter Binkley Tatem, better known as Sue Binkley in scientific circles. Born in Dayton, OH, but moved to Colorado in her high school years, Dr. Binkley received a BS in Biology from the University of Colorado at Boulder, where she met her future husband, Tim Binkley. Sue and Tim had a daughter, Shelley, before moving to Austin, TX, where Sue studied biological rhythms with Michael Menaker at the University of Texas. Sue and Tim separated in 1970 and Sue received her PhD in 1971. Her dissertation research extended the seminal studies in the Menaker Lab showing that surgical removal of the pineal gland of house sparrows, Passer domesticus, abolished free-running circadian locomotor rhythms by demonstrating that circadian patterns of core body temperature were similarly affected. Importantly, her research demonstrated the significance of physiological coupling among oscillators and their multiple outputs.

The temporal organization of biological activities by circadian clocks is pivotal for the survival of organisms. Significant progress has been made in understanding the molecular foundations of animal circadian clocks through the characterization of key components, such as CLOCK, BMAL1/Cycle (CYC), Period (PER), Timeless, and Cryptochrome (CRY) in several model organisms. To determine the extent of conservation of these elements, we investigated the sequences of these genes and their paralogs across 46 animal species that encompass multiple phyla in the Metazoan kingdom to resolve the relative timing of duplication and loss events that have diversified core clock components. Using analyses of orthology and protein-protein binding predictions, we identified and characterized elements in diverse animal species. Based on these analyses, we propose a circadian molecular mechanism employed by the ancestor of all animals. We also identify derived losses and expansions of circadian elements in smaller animal clades and provide insight into the evolutionary pressures faced by their ancestors to change such an important piece of internal machinery. Our study is the first systematic analysis of the deep phylogeny of nearly all major clades of extant animals.

In animals, the brain contains circadian clock neurons that regulate activity rhythms. The fruit fly Drosophila melanogaster exhibits a bimodal activity pattern characterized by two peaks, in the morning (M) and evening (E), known as the M and E peaks. These activity peaks are orchestrated by a network of approximately 240 clock neurons. The neuropeptide pigment-dispersing factor (PDF) is expressed in two sets of clock neurons, the large ventrolateral neurons (l-LNv) and the small ventrolateral neurons (s-LNv). Mutants of Pdf, as well as flies lacking PDF neurons, exhibit a characteristic E activity that is commonly simplified to a phase-advanced pattern under 12 h:12 h light-dark cycles. Previous studies have demonstrated that l-LNv neurons regulate the phase of the E peak; however, this effect is evident only under long photoperiod conditions. Therefore, the E peak phenotype observed in Pdf mutants remains incompletely explained. In this study, we employed genetic cell ablation and Pdf RNA interference using Gal4 lines specific to l-LNv neurons in a well-controlled genetic background. Under long photoperiod conditions, flies lacking l-LNv, s-LNv, or both neuronal groups exhibited an early termination of E activity prior to lights-off, resulting in a phase-advanced E peak. Similar results were obtained in Pdf knockdown flies. Notably, l-LNv neurons had a stronger effect on the timing of E activity termination than s-LNv neurons. These findings demonstrate that LNv neurons control the phase of E activity by modulating the timing of its offset, providing new insights into the neuronal mechanisms that shape daily activity patterns.

Circadian rhythms are endogenous oscillations that occur with a 24-h periodicity and support organismal homeostasis. While the role of the circadian clock in systemic vasculature is well known, its role in pulmonary vasculature, specifically in the pulmonary endothelium, has remained unexplored. We hypothesized that the circadian clock directly regulates pulmonary endothelium to control lung inflammation. Using pulmonary artery segments and endothelial cells isolated from mPer2luciferase transgenic mice, we monitored circadian rhythms and observed that lipopolysaccharide (LPS) treatment disrupted rhythmicity. This disruption was mediated by reactive oxygen species (ROS) generated via NADPH oxidase 2 (NOX2). Remarkably, the pharmacologic inhibition of NOX2 before LPS exposure restored circadian rhythmicity in the pulmonary endothelium. In wild-type (WT) mice, LPS activated an NOX2-NLRP3 signaling axis that drove inflammation, evidenced by increased polymorphonuclear neutrophil (PMN) accumulation and intercellular adhesion molecule-1 (ICAM-1) expression on the pulmonary endothelium. In contrast, disruption of the clock using two different clock mutants (Bmal1−/− and Cry1/2−/−) resulted in a sustained baseline elevation of PMN and ICAM-1, which changed minimally with LPS. This effect was attributed to aberrant activation of the NLRP3 inflammasome, as supported by lung transcriptomic data and reversal of the phenotype with an NLRP3 inhibitor. Importantly, these findings also reveal an intriguing bidirectional relationship: while the circadian clock modulates inflammatory responses, inflammatory stimuli in turn alter circadian rhythmicity via the NOX2 pathway. Together, our results identify a novel mechanism by which circadian control of pulmonary endothelial inflammation may be leveraged to mitigate the consequences of clock disruption in lung disease.