Weekly and seasonal variation in the circadian melatonin rhythm in humans:A response

We read with interest the commentary by Skeldon and Dijk about our article "Weekly, seasonal and chronotype-dependent variation of dim light melatonin onset." The discussion points raised by Skeldon and Dijk are currently among the most hotly debated in human circadian science. What external factors determine human phase of entrainment? How great is the contribution of natural versus artificial light and sun time versus social time? Our intra-individual data add to the still limited evidence from field studies in this matter. In their commentary, Skeldon and Dijk formulate two either-or hypotheses, postulating that humans entrain either solely to the natural light-dark cycle (sun time referenced by midday) (H1 ) or solely to the light selected by local clock time and social constraints (H2 ). Neither hypothesis accounts for the effect of season on human light exposure. We interpreted our findings along more complex lines, speculating that the 1-h earlier melatonin rise in summer found in our sample is likely the combined result of daylight saving time (DST)-induced behavioral advances and a stronger natural zeitgeber in summer (light exposure determined by social and seasonal factors, Horiginal ). Here, we show how the criticism by Skeldon and Dijk is based on two sentences quoted out of context (misrepresenting our hypothesis as H1 ) and that their hypothesis H2 leaves out important seasonal components in light exposure.</p

Relationship between chronotype and pain threshold in a sample of young healthy adults

Introduction: Chronotype indicates the biological preference for timing of activity and sleep. Being a late chronotype (ie, having a tendency for late sleep times) is associated with several mental and physical health problems. Previous studies found that late chronotypes are also more susceptible to chronic pain, but the relationship between chronotype and pain sensitivity remains unclear. Objectives: The aim of this study was to investigate the relationship between chronotype and heat pain threshold (as an indicator of pain sensitivity) in a sample of young healthy adults. Methods: We analyzed data from 316 young healthy adults participating in 4 different studies run at the Medical Faculty of the University of Augsburg. In all studies, chronotype and other sleep variables (eg, sleep duration) were assessed using the micro Munich ChronoType Questionnaire. Heat pain threshold was assessed with the method of adjustment. Results: Chronotype was not significantly associated with the heat pain threshold. Entering the other sleep variables in separate regression models did also not significantly explain variance in heat pain threshold. Conclusion: Our null findings are in contrast with previous notions that late chronotypes might be more sensitive to pain and more susceptible to chronic pain. Given the scarcity of the literature on this topic, more studies are needed to clarify the relationship between chronotype and pain sensitivity in different age populations, while also considering distinct pain modalities or other types of pain tests

Sleep improvements on days with later school starts persist after 1 year in a flexible start system

Early school times fundamentally clash with the late sleep of teenagers. This mismatch results in chronic sleep deprivation posing acute and long-term health risks and impairing students' learning. Despite immediate short-term benefits for sleep, the long-term effects of later starts remain unresolved. In a pre-post design over 1 year, we studied a unique flexible school start system, in which 10–12th grade students chose daily between an 8:00 or 8:50AM-start. Missed study time (8:00–8:50) was compensated for during gap periods or after classes. Based on 2 waves (6–9 weeks of sleep diary each), we found that students maintained their ~ 1-h-sleep gain on later days, longitudinally (n = 28) and cross-sectionally (n = 79). This gain was independent of chronotype and frequency of later starts but attenuated for boys after 1 year. Students showed persistently better sleep quality and reduced alarm-driven waking and reported psychological benefits (n = 93) like improved motivation, concentration, and study quality on later days. Nonetheless, students chose later starts only infrequently (median 2 days/week), precluding detectable sleep extensions in the flexible system overall. Reasons for not choosing late starts were the need to make up lost study time, preference for extra study time and transport issues. Whether flexible systems constitute an appealing alternative to fixed delays given possible circadian and psychological advantages warrants further investigation

COVID-19 related psychological burden and potential benefits of vaccination - data from a repeated cross-sectional survey in healthcare workers

The COVID-19 pandemic is impacting the psychological well-being, especially of health care workers, for more than two years now. Here, we followed-up on a survey we conducted at the very beginning of the pandemic, to determine potential changes in psychological strain experienced by health care workers one year later. Since our first survey in 2020, COVID-19 vaccines have been established, thus we assessed whether vaccination-status might modulate psychological burden of health care workers. We also collected data on resilience and sleep, as those might be related to successful coping. Between March and April 2021, nurses and physicians (N ​= ​286) working at the University Hospital Augsburg - with high or low exposure to COVID-19 patients - took part in an online survey. We found that fully vaccinated personnel reported lower levels of anxiety, depression, stress and exhaustion suggesting the potential positive consequences of vaccination beyond the obvious protection against a COVID-19 infection. Nurses reported more depressive symptoms, anxiety, stress and exhaustion and lower levels of job fulfilment than physicians. Individuals with high exposure to COVID-19 patients reported higher exhaustion and depersonalization. Resilience and sleep quality were significantly correlated with psychological and work-related burden, suggesting their potential role as protective resources. In general, the comparison of the present data to the survey conducted in 2020 suggests an overall increase of psychological burden in health care workers. Despite these surely alarming findings, it should be noted that being vaccinated might come along with reduced psychological strain

A 4-year longitudinal study investigating the relationship between flexible school starts and grades

The mismatch between teenagers’ late sleep phase and early school start times results in acute and chronic sleep reductions. This is not only harmful for learning but may reduce career prospects and widen social inequalities. Delaying school start times has been shown to improve sleep at least short-term but whether this translates to better achievement is unresolved. Here, we studied whether 0.5–1.5 years of exposure to a flexible school start system, with the daily choice of an 8 AM or 8:50 AM-start, allowed secondary school students (n = 63–157, 14–21 years) to improve their quarterly school grades in a 4-year longitudinal pre-post design. We investigated whether sleep, changes in sleep or frequency of later starts predicted grade improvements. Mixed model regressions with 5111–16,724 official grades as outcomes did not indicate grade improvements in the flexible system per se or with observed sleep variables nor their changes—the covariates academic quarter, discipline and grade level had a greater effect in our sample. Importantly, our finding that intermittent sleep benefits did not translate into detectable grade changes does not preclude improvements in learning and cognition in our sample. However, it highlights that grades are likely suboptimal to evaluate timetabling interventions despite their importance for future success

Gain of function of mutant p53: The mutant p53/NF-Y protein complex reveals an aberrant transcriptional mechanism of cell cycle regulation

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Lower school performance in late chronotypes: underlying factors and mechanisms

Success at school determines future career opportunities. We described a time-of-day specific disparity in school performance between early and late chronotypes. Several studies showed that students with a late chronotype and short sleep duration obtain lower grades, suggesting that early school starting times handicap their performance. How chronotype, sleep duration, and time of day impact school performance is not clear. At a Dutch high school, we collected 40,890 grades obtained in a variety of school subjects over an entire school year. We found that the strength of the effect of chronotype on grades was similar to that of absenteeism, and that late chronotypes were more often absent. The difference in grades between the earliest 20% and the latest 20% of chronotypes corresponds to a drop from the 55th to 43rd percentile of grades. In academic subjects using mainly fluid cognition (scientific subjects), the correlation with grades and chronotype was significant while subjects relying on crystallised intelligence (humanistic/linguistic) showed no correlation with chronotype. Based on these and previous results, we can expand our earlier findings concerning exam times: students with a late chronotype are at a disadvantage in exams on scientific subjects, and when they are examined early in the day

Biochemical and cellular studies of three human 3‐phosphoglycerate dehydrogenase variants responsible for pathological reduced L‐serine levels

In the brain, the non-essential amino acid L-serine is produced through the phosphorylated pathway (PP) starting from the glycolytic intermediate 3-phosphoglycerate: among the different roles played by this amino acid, it can be converted into D-serine and glycine, the two main co-agonists of NMDA receptors. In humans, the enzymes of the PP, namely phosphoglycerate dehydrogenase (hPHGDH, which catalyzes the first and rate-limiting step of this pathway), 3-phosphoserine aminotransferase, and 3-phosphoserine phosphatase are likely organized in the cytosol as a metabolic assembly (a "serinosome"). The hPHGDH deficiency is a pathological condition biochemically characterized by reduced levels of L-serine in plasma and cerebrospinal fluid and clinically identified by severe neurological impairment. Here, three single-point variants responsible for hPHGDH deficiency and Neu-Laxova syndrome have been studied. Their biochemical characterization shows that V261M, V425M, and V490M substitutions alter either the kinetic (both maximal activity and Km for 3-phosphoglycerate in the physiological direction) and the structural properties (secondary, tertiary, and quaternary structure, favoring aggregation) of hPHGDH. All the three variants have been successfully ectopically expressed in U251 cells, thus the pathological effect is not due to hindered expression level. At the cellular level, mistargeting and aggregation phenomena have been observed in cells transiently expressing the pathological protein variants, as well as a reduced L-serine cellular level. Previous studies demonstrated that the pharmacological supplementation of L-serine in hPHGDH deficiencies could ameliorate some of the related symptoms: our results now suggest the use of additional and alternative therapeutic approaches