Seasonal daylength, or circadian photoperiod, is a pervasive environmental signal that profoundly influences physiology and behavior. In mammals, the central circadian clock resides in the suprachiasmatic nuclei (SCN) of the hypothalamus where it receives retinal input and synchronizes, or entrains, organismal physiology and behavior to the prevailing light cycle. The process of entrainment induces sustained plasticity in the SCN, but the molecular mechanisms underlying SCN plasticity are incompletely understood. Entrainment to different photoperiods persistently alters the timing, waveform, period, and light resetting properties of the SCN clock and its driven rhythms. To elucidate novel candidate genes for molecular mechanisms of photoperiod plasticity, we performed RNA sequencing on whole SCN dissected from mice raised in long (light:dark [LD] 16:8) and short (LD 8:16) photoperiods. Fewer rhythmic genes were detected in mice subjected to long photoperiod, and in general, the timing of gene expression rhythms was advanced 4-6 h. However, a few genes showed significant delays, including Gem. There were significant changes in the expression of the clock-associated gene Timeless and in SCN genes related to light responses, neuropeptides, gamma aminobutyric acid (GABA), ion channels, and serotonin. Particularly striking were differences in the expression of the neuropeptide signaling genes Prokr2 and Cck, as well as convergent regulation of the expression of 3 SCN light response genes, Dusp4, Rasd1, and Gem. Transcriptional modulation of Dusp4 and Rasd1 and phase regulation of Gem are compelling candidate molecular mechanisms for plasticity in the SCN light response through their modulation of the critical NMDAR-MAPK/ERK-CREB/CRE light signaling pathway in SCN neurons. Modulation of Prokr2 and Cck may critically support SCN neural network reconfiguration during photoperiodic entrainment. Our findings identify the SCN light response and neuropeptide signaling gene sets as rich substrates for elucidating novel mechanisms of photoperiod plasticity. Data are also available at http://circadianphotoperiodseq.com/, where users can view the expression and rhythmic properties of genes across these photoperiod conditions.

Time is an extremely important element in the field of GNSS positioning. In precise positioning with a single-centimetre accuracy, satellite clock corrections are used. In this article, the longest available data set of satellite clock corrections of four GNSS systems from 2014 to 2021 was analysed. This study covers the determination of the quality (outliers number and magnitude), availability, stability, and determination of the specificity and nature of the clock correction for each satellite system. One problem with the two newest satellite systems (Galileo and BeiDou) is the lack of availability of satellite signals in the early years of the analysis. These data were available only in the later years of the period covered by the analysis, as most of the satellites have only been in orbit since 2018-2019. Interestingly, the percentage of outlying observations was highest in Galileo and lowest in BeiDou. Phase and frequency plots showed a significant number of outlying observations. On the other hand, after eliminating outlying observations, each system showed a characteristic graph waveform. The most consistent and stable satellite clock corrections are provided by the GPS and GLONASS systems. The main problems discussed in this paper are the determination of the number and magnitude of outliers in clock products of four GNSS systems (GPS, GLONASS, Galileo, Beidou) and the study on the long-term stability of GNSS clocks analysis, which covers the years 2014-2021.

Obesity and overweight represent a growing health problem worldwide. Genes regulating the intake and metabolism of different nutrients can positively or negatively influence the efficacy of nutritional interventions against obesity and its complications. The aim of this study was to assess changes in anthropometric and clinical parameters and the adherence to a Mediterranean diet (MedDiet) over time in relation to nutrigenetic variants in overweight or obese subjects affected by Type 2 Diabetes (T2D) or dysglycemia, who were included in a nutritional program. A total of 23 subjects were included in this study. Clinical parameters, physical activity levels, and the adherence to a MedDiet were evaluated at baseline, at 6 (T6), and at 12 months (T12) during and after a diet/lifestyle intervention. In a single blood sample from each subject, rs1984112 (A>G) and rs1761667 (G>A) in CD36; rs7950226 (G>A) in BMAL1; and rs1801260 (A>G), rs4864548 (A>G), and rs3736544 (G>A) in CLOCK were genotyped with Real-Time PCR. Significant associations were observed between CD36 rs1761667 and weight (p = 0.025), hip circumference (p = 0.042), triglycerides (p = 0.047), and HbA1c (p = 0.012) at baseline. Moreover, the genotype AA in CD36 rs1761667 was significantly associated with a lower BMI when compared to G carriers at baseline, at T6, and also at T12. In addition, subjects with the AA genotype at CD36 rs1984112 had significantly lower levels of HbA1c (p = 0.027) than the GG and AG genotypes at baseline. These results show that variants in CD36 can have an impact on anthropometric and clinical parameters in overweight or obese subjects affected by T2D or dysglycemia, and that it might influence the success of the diet/lifestyle intervention.

The aim of the pilot project was to research relationships between the occurrence and level of intensity of primitive reflexes in primary school children, the ability to read an analogue clock and to tell the time. A group of 28 children (14 girls and 14 boys) who attended Montessori Primary School was examined. In the first stage, participants were assessed for the presence of five primitive reflexes (PR): the asymmetrical tonic neck reflex (ATNR), symmetrical tonic neck reflex (STNR), spinal Galant reflex, tonic labyrinthine reflex (TLR) and Palmar grasp reflex. Romberg\'s test was employed to identify signs of difficulties with control of balance and/or proprioception. In the second stage, pupils underwent tests that challenged their ability to read a clock and calculate passing time. After summing up points obtained for all tests, a correlation coefficient was made from which the results were derived. There is a negative correlation between the ability to read an analogue clock and the continued presence of some primitive reflexes. Lower neuromotor maturity (higher points of PR) correlates with lower ability to read a clock. The highest correlations between difficulty with telling the time were found with persistence of the STNR, ATNR and Romberg\'s test.

BACKGROUND: Cancer-related fatigue (CRF) is one of the most common and distressing complaints reported by cancer patients during chemotherapy considerably impacting all aspects of a patient\'s life (physical, psychosocial, professional, and socioeconomic). The aim of this study was to assess the severity of cancer-related fatigue in a group of breast cancer patients undergoing chemotherapy and explore the association between fatigue scores and sociodemographic, clinical, biological, psychiatric, and genetic factors.
METHODS: A cross-sectional pilot study carried out at the oncology outpatient unit of Hôtel-Dieu de France University Hospital recruited 67 breast cancer patients undergoing chemotherapy between November 2017 and June 2019 to evaluate fatigue using the EORTC QLQ-C30 scale (European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire). Genotyping for seven gene polymorphisms (COMT, DRD2, OPRM1, CLOCK, PER2, CRY2, ABCB1) was performed using the Lightcycler® (Roche).
RESULTS: The prevalence of fatigue was 46.3%. Multivariable analysis taking the fatigue score as the dependent variable showed that a higher number of cycles and a lower hemoglobin level were significantly associated with higher odds of exhibiting fatigue. Moreover, having at least one C allele for DRD2 SNP (vs. TT) was significantly associated with a 4.09 higher odds of expressing fatigue compared to TT patients. Finally, patients with at least one C allele for CLOCK SNP tended to display higher fatigue levels than TT patients.
CONCLUSIONS: Our study showed that anemic breast cancer patients with a high number of chemotherapy cycles and those carrying at least one C allele for DRD2 and CLOCK SNPs are at greater risk of exhibiting fatigue. Since no previous research has reported such genetic results, future studies are necessary to confirm our findings.

Abnormalities of lipid metabolism in the form of high fasting as well as postprandial triglyceride levels immediately after night shift work and under simulated night shift conditions have been reported in the literature. Whether dysregulation of circadian genes in the long term is associated with abnormal triglyceride metabolism has not been previously investigated. This pilot study aimed to investigate the long-term effect of rotational night shift work on the expression of circadian genes among healthcare workers and to ascertain the association between the expression of circadian genes and postprandial triglyceride and insulin resistance parameters. The study was conducted on two groups of healthcare workers (n = 20/group). Group 1 included day shift workers who had not done night shift duty during the past one year or ever. Group 2 included healthcare workers doing rotational night shift duties (≥4 night shift duties/month). Fasting blood samples were collected at 08:00 h to study the expression of circadian genes CLOCK, NPAS2, BMAL1, CRY1, CRY2, PER1, PER2, PER3, REVERBα, and biochemical parameters after which a standardized fat challenge test was done to measure postprandial triglyceride levels. Study of Group 2 individuals was conducted after a minimum of one week after the last night shift duty. Expression of CLOCK, NPAS2, PER1, PER3, and REV-ERBα genes was higher in Group 2 compared to Group 1 subjects, and expression of BMAL1 and CRY1 genes were lower in Group 2 compared to Group 1. Several of these genes showed significant correlations with postprandial triglyceride and insulin resistance parameters in Group 2 but not in Group 1 subjects. The present study showed altered expression of several circadian genes in healthcare workers involved in rotational night shift duties associated with postprandial triglyceride and insulin resistance parameters. This study therefore suggests that long term circadian gene dysregulation could have serious metabolic consequences in individuals engaged in rotational night shift duties.

The exposure to endocrine disruptors and the disruption of the circadian rhythms can both affect thyroid hormones, with results that are most likely carcinogenic in humans. The effects of cadmium (Cd) level and circadian-related single-nucleotide polymorphisms (SNPs) on thyroid cancer (TC) risk have rarely been reported. In this study, the associations of urine Cd, CLOCK gene polymorphisms, and TC risk were evaluated, in addition to the effect of the gene-environment interaction on TC risk. In this case-control study, 218 TC cases and 218 controls were enrolled. Cd in urinary samples was determined by atomic absorption spectrometry. Three SNPs (rs3805151, rs3805154, and rs78929565) were genotyped with an improved multiplex ligation detection reaction technique. The individuals with a high Cd level were 1.72-fold more likely to have TC (OR = 1.72, 95%CI 1.04-2.85), and a high Cd level was associated with higher tumor T stage and N stage (OR = 2.42, 95%CI 1.28-4.58; OR = 3.26, 95%CI 1.67-6.33, respectively). Individuals with TT genotype of rs78929565 had a 107 % increase in TC risk (OR = 2.07, 95%CI 1.00-4.29). Cases with CT genotype tended to have a higher AJCC stage (OR = 2.79, 95% CI 1.01-7.78). A significant interaction was detected between the rs78929565 variant and Cd exposure (p interaction = 0.04). The TT genotype carriers of rs78929565 with a high Cd level were more susceptible to thyroid cancer than the major homozygotes carriers who were exposed to a low cadmium level (OR = 2.66, 95%CI 1.07-6.59). These findings suggested that Cd exposure and the CLOCK variant genotypes were associated with TC risk and tumor severity. Individuals with minor allele of rs78929565 and higher Cd exposure had increased susceptibility to TC. Further studies are required to confirm these findings.

Recent advances in the technology of \"aging clocks\" based on DNA methylation suggest that it may be possible to measure changes in the rate of human aging over periods as short as a year or two. To the extent that methylation (and other biomarkers) are valid surrogates for biological age, the testing of antiaging interventions has thus become radically cheaper, faster, and more practical. Together with colleagues at UCLA, I have initiated a clinical trial to evaluate some of the most popular antiaging strategies currently deployed by \"early adopters\" in the lay community of personal health activists. We are recruiting 5000 subjects, age 45-65, and interviewing them in detail about their diet, drugs and supplements, exercise, social, and other practices that plausibly contribute to modulate the rate of aging. They agree to submit blood samples for analysis of methylation age at the beginning, middle, and end of a 2-year test period. Primary endpoint is the difference in methylation age over the course of 2 years. We are in the process of developing a specialized clock, optimized for individual differences over time. Results will be viewed as an exploratory study to identify synergistic combinations of age-retarding treatments. It is our expectation that there is a great deal of redundancy in the strategies that have been researched and promoted to the aware public; thus, most combinations can retard the rate of aging by only a few percent, consistent with the best known single measures. However, we hope that among the many strategies that our subjects have adopted, there will be some combinations that synergize and achieve age retardation by ≥25% or more. A mock-up analysis of computer-generated data has been performed to fix parameters of the study, and confirm that such combinations will be able to be detected with good probability, should they exist. All data (redacted for privacy) will be open sourced, available to the scientific community and to the public.

BACKGROUND: Cluster headache (CH), a rare primary headache disorder, is currently thought to be a genetic susceptibility which play a role in CH susceptibility. A large numbers of genetic association studies have confirmed that the HCRTR2 (Hypocretin Receptor 2) SNP rs2653349, and the ADH4 (Alcohol Dehydrogenase 4) SNP rs1126671 and rs1800759 polymorphisms are linked to CH. In addition, the CLOCK (Circadian Locomotor Output Cycles Kaput) gene is becoming a research hotspot for CH due to encoding a transcription factor that serves as a basic driving force for circadian rhythm in humans. The purpose of this study was to evaluate the association between CH and the HCRTR2, ADH4 and CLOCK genes in a Chinese CH case-control sample.
METHODS: We genotyped polymorphisms of nine single nucleotide polymorphisms (SNPs) in the HCRTR2, ADH4 and CLOCK genes to perform an association study on a Chinese Han CH case-control sample (112 patients and 192 controls),using Sequenom MALDI-TOF mass spectrometry iPLEX platform. The frequencies and distributions of genotypes and haplotypes were statistically compared between the case and control groups to identify associations with CH. The effects of SNPs on CH were further investigated by multiple logistic regression.
RESULTS: The frequency of the HCRTR2 SNP rs3800539 GA genotype was significantly higher in cases than in controls (48.2% vs.37.0%). The GA genotypes was associated with a higher CH risk (OR = 1.483, 95% CI: 0.564-3.387, p = 0.038), however, after Bonferroni correction, the association lost statistical significance. Haplotype analysis of the HCRTR2 SNPs showed that among eight haplotypes, only H1-GTGGGG was linked to a reduced CH risk (44.7% vs. 53.1%, OR = 0.689, 95% CI =0.491~0.966, p = 0.030). No significant association of ADH4, CLOCK SNPs with CH was statistically detected in the present study.
CONCLUSIONS: Association between HCRTR2, ADH4,CLOCK gene polymorphisms and CH was not significant in the present study, however, haplotype analysis indicated H1-GTGGGG was linked to a reduced CH risk.

The 3111T/C single nucleotide polymorphism (SNP) of Circadian Locomotor Output Cycles Kaput (CLOCK) gene reportedly affects gastric motility before breakfast. It is of interest to know whether this SNP can affect the motility during the daytime. We investigated the association between the CLOCK 3111T/C SNP and several gastric motility parameters during the time period from 8:00 to 20:00 in 34 young women with scheduled meals. There were similar daytime fluctuations in gastric motility before and after the meals between the major (T/T) and minor (T/C) allele carriers. The CLOCK SNP may affect daytime gastric motility less than food stimulation.