The influence of time of day on memory recognition for faces.

Time of day can alter memory performance in general. Its influence on memory recognition performance for faces, which is important for daily encounters with new persons or testimonies, has not been investigated yet. Importantly, high levels of the stress hormone cortisol impair memory recognition, in particular for emotional material. However, some studies also reported high cortisol levels to enhance memory recognition. Since cortisol levels in the morning are usually higher than in the evening, time of day might also influence recognition performance. In this pre-registered study with a two-day design, 51 healthy men encoded pictures of male and female faces with distinct emotional expressions on day one around noon. Memory for the faces was retrieved two days later at two consecutive testing times either in the morning (high and moderately increased endogenous cortisol levels) or in the evening (low endogenous cortisol levels). Additionally, alertness as well as salivary cortisol levels at the different timepoints was assessed. Cortisol levels were significantly higher in the morning compared to the evening group as expected, while both groups did not differ in alertness. Familiarity ratings for female stimuli were significantly better when participants were tested during moderately increased endogenous cortisol levels in the morning than during low endogenous cortisol levels in the evening, a pattern which was previously also observed for stressed versus non-stressed participants. In addition, cortisol levels during that time in the morning were positively correlated with the recollection of face stimuli in general. Thus, recognition memory performance may depend on the time of day and as well as on stimulus type, such as the difference of male and female faces. Most importantly, the results suggest that cortisol may be meaningful and worth investigating when studying the effects of time of day on memory performance. This research offers both, insights into daily encounters as well as legally relevant domains as for instance testimonies.

Time-Restricted Eating Benefits on Pulmonary Function and Postural Balance in Overweight or Obese Women.

This study aimed to evaluate the impact of time-restricted eating (TRE) on neuro-physiological parameters, objective and subjective sleep, pulmonary capacity, and postural balance among women with excess body weight. METHODS: Thirty-one participants were assigned to either a TRE group (n = 15, 28.74 ± 9.25 years, 88.32 ± 13.38 kg, and 32.71 ± 5.15 kg/m2), engaging in ad libitum 16 h fasting over a 12-week period, or a control group (CG, n = 16, 36.25 ± 11.52 years, 90.88 ± 19.01 kg, and 33.66 ± 6.18 kg/m2). The assessment of heart rate variability (HRV), spirometric parameters (forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), FEV1/ FVC ratio, objective and subjective sleep assessments employing actigraphy and the Epworth Sleepiness Scale, and postural balance using the Y balance test (YBT) were conducted before and after the intervention. RESULTS: No significant negative effects of TRE were observed for HRV and objective sleep parameters. Only the TRE group improved FEV1 in both sitting (p < 0.0005) and supine positions (p = 0.001). Furthermore, the TRE group showed improvement in postural balance performance compared to the CG in anterior (p = 0.03), postero-medial (p = 0.04), and postero-lateral directions (p = 0.003). CONCLUSION: This study highlights TRE as a feasible and safe dietary intervention with significant improvements in postural balance and pulmonary function, without any negative impact on HRV or objective sleep assessments among overweight or obese women.

Light sampling behaviour regulates circadian entrainment in mice.

BACKGROUND: The natural light environment is far more complex than that experienced by animals under laboratory conditions. As a burrowing species, wild mice are able to self-modulate their light exposure, a concept known as light environment sampling behaviour. By contrast, under laboratory conditions mice have little opportunity to exhibit this behaviour. To address this issue, here we introduce a simple nestbox paradigm to allow mice to self-modulate their light environment. Dark nestboxes fitted with passive infrared sensors were used to monitor locomotor activity, circadian entrainment, decision making and light environment sampling behaviour. RESULTS: Under these conditions, mice significantly reduce their light exposure to an average of just 0.8 h across a 24 h period. In addition, mice show a distinct pattern of light environment sampling behaviour, with peaks at dawn and dusk under a ramped light dark cycle. Furthermore, we show that the timing of light environment sampling behaviour depends upon endogenous circadian rhythms and is abolished in mice lacking a circadian clock, indicating a feedback loop between light, the circadian clock and behaviour. CONCLUSIONS: Our results highlight the important role of behaviour in modifying the light signals available for circadian entrainment under natural conditions.

Role of Circadian Rhythm Changes on Functional Dependence Despite Successful Repercussion in Patients with Endovascular Treatment.

BACKGROUND: Increasing evidence of circadian biology may influence the physiopathologic mechanism, progression, and recovery of stroke. However, few data have shown about circadian rhythm on futile recanalization (FR) in patients treated with endovascular treatment (EVT). METHODS: From 2017 to 2021, an observational cohort of acute ischemic stroke (AIS) patients with large vessel occlusion (LVO) underwent EVT was conducted. FR was defined as the failure to achieve functional independence in patients at 90 days after EVT, although the occluded vessels reached a recanalization. The effect of circadian rhythm on FR was investigated using the logistic regression model. RESULTS: Of 783 patients, there were 149 patients who had stroke onset between 23:00-6:59, 318 patients between 7:00-14:59, and 316 patients between 15:00-22:59. Patients suffered a stroke during 15:00-22:59 had shorter OTP (p =0.001) time, shorter OTR (p<0.001) time, higher rate of intravenous thrombolysis (p =0.001) than groups of other time intervals. The rate of FR post-EVT in patients who had a stroke between 15:00-22:59 was significantly higher than in those with stroke onset between 23:00-6:59 (p =0.017). After adjusting for confounding factors, the time of stroke occurring during 15:00-22:59 (adjusted OR [aOR], 1.652; 95%CI, 1.024-2.666, p =0.04) was an independent predictor of FR. CONCLUSION: Circadian rhythm can directly or indirectly affect the occurrence, development, and prognosis of AIS. More studies may be needed in the future to validate the results of our study and to explore the potential mechanisms behind the effects of circadian rhythms on FR.

Assessing sleep in primary brain tumor patients using smart wearables and patient-reported data: Feasibility and interim analysis of an observational study.

Background: Sleep-wake disturbances are common and disabling in primary brain tumor (PBT) patients but studies exploring longitudinal data are limited. This study investigates the feasibility and relationship between longitudinal patient-reported outcomes (PROs) and physiologic data collected via smart wearables. Methods: Fifty-four PBT patients ≥ 18 years wore Fitbit smart-wearable devices for 4 weeks, which captured physiologic sleep measures (eg, total sleep time, wake after sleep onset [WASO]). They completed PROs (sleep hygiene index, PROMIS sleep-related impairment [SRI] and Sleep Disturbance [SD], Morningness-Eveningness Questionnaire [MEQ]) at baseline and 4 weeks. Smart wearable use feasibility (enrollment/attrition, data missingness), clinical characteristics, test consistency, PROs severity, and relationships between PROs and physiologic sleep measures were assessed. Results: The majority (72%) wore their Fitbit for the entire study duration with 89% missing < 3 days, no participant withdrawals, and 100% PRO completion. PROMIS SRI/SD and MEQ were all consistent/reliable (Cronbach's alpha 0.74-0.92). Chronotype breakdown showed 39% morning, 56% intermediate, and only 6% evening types. Moderate-severe SD and SRI were reported in 13% and 17% at baseline, and with significant improvement in SD at 4 weeks (P = .014). Fitbit-recorded measures showed a correlation at week 4 between WASO and SD (r = 0.35, P = .009) but not with SRI (r = 0.24, P = .08). Conclusions: Collecting sleep data with Fitbits is feasible, PROs are consistent/reliable, > 10% of participants had SD and SRI that improved with smart wearable use, and SD was associated with WASO. The skewed chronotype distribution, risk and impact of sleep fragmentation mechanisms warrant further investigation. Trial Registration: NCT04 669 574.

Transcriptome Analysis Revealed ZmPTOX1 Is Required for Seedling Development and Stress Tolerance in Maize.

Plant seedling morphogenesis is considerably related to photosynthesis, pigment synthesis, and circadian periodicity during seedling development. We identified and cloned a maize zebra or crossbanding leaves mutant wk3735, which produces pale white kernels and was identified and plays a role in the equilibrium of the Redox state the in/out of ETC by active oxygen scavenging. Interestingly, it produces the zebra leaves during the production of the first seven leaves, which is apparently different from the mutation of homologs AtPTOX in Arabidopsis. It is intriguing to investigate how and why yellow crossbands (zebra leaf phenotype) emerge on leaves. As expected, chlorophyll concentration and photosynthetic efficiency both significantly declined in the yellow sector of wk3735 leaves. Meanwhile, we observed the circadian expression pattern of ZmPTOX1, which was further validated by protein interaction assays of the circadian clock protein TIM1 and ZmPTOX1. The transcriptome data of yellow (muW) and green (muG) sectors of knock-out lines and normal leaves of overexpression lines (OE) at the 5th-leaf seedling stage were analyzed. Zebra leaf etiolated sections exhibit a marked defect in the expression of genes involved in the circadian rhythm and rhythmic stress (light and cold stress) responses than green sections. According to the analysis of co-DEGs of muW vs. OE and muG vs. OE, terms linked to cell repair function were upregulated while those linked to environmental adaptability and stress response were downregulated due to the mutation of ZmPTOX1. Further gene expression level analyses of reactive oxygen species (ROS) scavenging enzymes and detection of ROS deposition indicated that ZmPTOX1 played an essential role in plant stress resistance and ROS homeostasis. The pleiotropic roles of ZmPTOX1 in plant ROS homeostasis maintenance, stress response, and circadian rhythm character may collectively explain the phenotype of zebra leaves during wk3735 seedling development.

Machine learning reveals the transcriptional regulatory network and circadian dynamics of Synechococcus elongatus PCC 7942.

Synechococcus elongatus is an important cyanobacterium that serves as a versatile and robust model for studying circadian biology and photosynthetic metabolism. Its transcriptional regulatory network (TRN) is of fundamental interest, as it orchestrates the cell's adaptation to the environment, including its response to sunlight. Despite the previous characterization of constituent parts of the S. elongatus TRN, a comprehensive layout of its topology remains to be established. Here, we decomposed a compendium of 300 high-quality RNA sequencing datasets of the model strain PCC 7942 using independent component analysis. We obtained 57 independently modulated gene sets, or iModulons, that explain 67% of the variance in the transcriptional response and 1) accurately reflect the activity of known transcriptional regulations, 2) capture functional components of photosynthesis, 3) provide hypotheses for regulon structures and functional annotations of poorly characterized genes, and 4) describe the transcriptional shifts under dynamic light conditions. This transcriptome-wide analysis of S. elongatus provides a quantitative reconstruction of the TRN and presents a knowledge base that can guide future investigations. Our systems-level analysis also provides a global TRN structure for S. elongatus PCC 7942.

Abnormal circadian rhythms exacerbate dilated cardiomyopathy by reducing the ventricular mechanical strength.

AIMS: Dilated cardiomyopathy (DCM) has etiological and pathophysiological heterogeneity. Abnormal circadian rhythm (ACR) is related to the development of DCM in animal models, but exploration based on clinical samples is lacking. Sleep apnea (SA) is the most common disease related to ACR, and we chose SA as the study object to explore ACR-DCM. METHODS AND RESULTS: We included a derivation cohort (n =105) and a validation cohort (n = 65). DCM patients were divided into SA and without SA group. RT-qPCR was used to determine the change of rhythm gene expression pattern of heart samples from different timepoints. We used single-nucleus RNA sequencing (snRNA-seq) to explore the abnormal transcriptional patterns in the ACR group, and we verified the findings by pathological staining, atomic force microscopy (AFM), and Rev-erbα/ß knockout (KO) mice analysis. DCM patients with SA showed decreased amplitude of rhythm gene expression. SA group showed more severe dilation of left heart chambers. From snRNA-seq, ACR-DCM lost the morning transcriptional patterns, detailly, actin cytoskeleton organization of cardiomyocytes (CMs) disrupted and hypertrophy aggravated, and the proportion of activated fibroblasts (Fibs) decreased with the reduction of fibrotic area ratio. The results of pathological staining, mechanical experiments, and transcriptional feature of Rev-erbα/ß KO mice supported the above findings. CONCLUSION: Compared with the non-SA group, left ventricular (LV) wall dilation was more severe and the structural strength was lower in DCM patients with SA, and phenotypic changes in CM and Fib were involved in this process. ACR-DCM was histopathologically characterized by a structurally weak ventricular wall.

Circadian regulatory networks of glucose homeostasis and its disruption as a potential cause of under-nutrition.

The circadian clock system, an evolutionarily conserved mechanism, orchestrates diurnal rhythms in biological activities such as behavior and metabolism, aligning them with the earth's 24-hour light/dark cycle. This synchronization enables organisms to anticipate and adapt to predictable environmental changes, including nutrient availability. However, modern lifestyles characterized by irregular eating and sleeping habits disrupt this synchrony, leading to metabolic disorders such as obesity and metabolic syndrome, evidenced by higher obesity rates among shift workers. Conversely, circadian disturbances are also associated with reduced nutrient absorption and an increased risk of malnutrition in populations such as the critically ill or the elderly. The precise mechanisms of these disturbances in leading to either over-nutrition or under-nutrition is complex and not yet fully understood. Glucose, a crucial energy source, is closely linked to obesity when consumed excessively and to weight loss when intake is reduced, which suggests that circadian regulation of glucose metabolism is a key factor connecting circadian disturbances with nutritional outcomes. In this review, we describe how the biological clock in various tissues regulates glucose metabolism, with a primary focus on studies utilizing animal models. Additionally, we highlight current clinical evidence supporting the association between circadian disturbance and glucose metabolism, arguing that such disruption could predominantly contribute to under-nutrition due to impaired efficient utilization of nutrients.

Sleep disorder syndromes of post-acute sequelae of SARS-CoV-2 (PASC) / Long Covid.

INTRODUCTION: COVID-19 infection has resulted in a high prevalence of a post-infectious syndrome, known as post-acute sequelae of SARS-CoV-2 (PASC) or "Long COVID". PASC is a heterogeneous disease with a high prevalence of sleep disturbances, varying from an insomnia disorder to excessive daytime sleepiness. METHODS: Patients seen in the Covid Survivorship Program at the Beth Israel Deaconess Medical Center Boston, USA, were screened for sleep disorders as part of a comprehensive multi-system evaluation. Those who screened positive were referred for a comprehensive sleep evaluation in a dedicated COVID-19-Sleep clinic, followed by diagnostic sleep testing and treatment. This report summarizes patients who completed an American Academy of Sleep Medicine (AASM) accredited facility-based diagnostic evaluation. International Classification of Sleep Disorders 3rd Edition-Revised criteria were met for all diagnoses. RESULTS: In 42 patients with PASC, five categories of sleep disorder syndromes were observed following a sleep clinic evaluation, including obstructive sleep apnea, chronic insomnia disorder, primary hypersomnia, REM behavior disorder (RBD), and new onset circadian phase delay. Seven patients met criteria for idiopathic hypersomnia, and two had narcolepsy type 2. RBD patients were infected in three different waves; circadian disturbance patients were all infected in the winter wave of 2020/21, and the primary hypersomnolence group occurred during all waves, predominantly the initial wave of 2020. A peculiar form of insomnia was a persistent loss of sleep regularity. CONCLUSIONS: Specific sleep symptoms/syndromes are reported in this select group of patients with PASC/Long Covid. As new onset sleep complaints are prevalent in PASC, we recommend a complete clinical and investigative sleep evaluation for persistent severe sleep symptoms following COVID-19 infection.

Effects of Music on Repeated-Sprint Performance of Elite Tunisian Soccer Players: Comparing Morning to Afternoon Practice Sessions.

Our aim in the present study was to examine the effect of listening to self-selected music during soccer warm-ups in morning and afternoon sessions on repeated-sprint performances of elite soccer players. Twenty elite academy male soccer players performed a repeated-sprint ability (RSA) test in the morning (i.e., 07:00 hours) and in the afternoon (i.e., 17:00 hours), with or without listening to music during the warm-up period. The RSA test consisted of six 40-meter sprints with 180° direction changes interspersed with a 20-second passive recovery period. Ratings of perceived exertion (RPE) were obtained at the end of the warm-up period and immediately after the RSA test. Results showed that listening to music during warming-up had no significant effect on these selected performance measures (i.e., mean sprint time, best sprint time, RSA decrement), regardless of whether performances were in the morning or the afternoon. Moreover, players reported higher post-warm-up RPE scores in the music listening condition than in the no-music listening condition, only in the afternoon session. Furthermore, RPE scores measured after the RSA test were higher in the no-music listening condition compared to the music listening condition, only in the morning session. Thus, the use of music during warming-up in elite soccer players appears to be an individual athlete's choice but not a reliable means of enhancing performance.

Sleep debt-induced anxiety and addiction to substances of abuse: A narrative review.

Substance Use Disorder (SUD) has been conceptualized as an outcome of a dysregulated reward system. However, individuals with SUD suffer from anxiety with an intensity depending on the abstinence period length. This review discusses the role of anxiety as a major contributor to the initiation and perpetuation of SUD, and its dependence on an up-regulated defense-antireward system. In addition, it is discussed that sleep debt, and its psychosocial consequences, promote anxiety, contributing to SUD generation and maintenance. Healthy sleep patterns can be disrupted by diverse medical conditions and negative psychosocial interactions, resulting in accumulated sleep debt and anxiety. Within this narrative review, we discuss the interplay between the motivation-reward and defense-antireward systems, framing the progression from recreational drug use to addiction. This interplay is nuanced by sleep debt-induced anxiety and its psychosocial consequences as contributory vulnerability factors in the genesis of addiction.

Circadian rhythms and breast cancer: from molecular level to therapeutic advancements.

BACKGROUND AND OBJECTIVES: Circadian rhythms, the endogenous biological clocks that govern physiological processes, have emerged as pivotal regulators in the development and progression of breast cancer. This comprehensive review delves into the intricate interplay between circadian disruption and breast tumorigenesis from multifaceted perspectives, encompassing biological rhythms, circadian gene regulation, tumor microenvironment dynamics, and genetic polymorphisms. METHODS AND RESULTS: Epidemiological evidence underscores the profound impact of external factors, such as night shift work, jet lag, dietary patterns, and exercise routines, on breast cancer risk and progression through the perturbation of circadian homeostasis. The review elucidates the distinct roles of key circadian genes, including CLOCK, BMAL1, PER, and CRY, in breast cancer biology, highlighting their therapeutic potential as molecular targets. Additionally, it investigates how circadian rhythm dysregulation shapes the tumor microenvironment, fostering epithelial-mesenchymal transition, chronic inflammation, and immunosuppression, thereby promoting tumor progression and metastasis. Furthermore, the review sheds light on the association between circadian gene polymorphisms and breast cancer susceptibility, paving the way for personalized risk assessment and tailored treatment strategies. CONCLUSIONS: Importantly, it explores innovative therapeutic modalities that harness circadian rhythms, including chronotherapy, melatonin administration, and traditional Chinese medicine interventions. Overall, this comprehensive review emphasizes the critical role of circadian rhythms in the pathogenesis of breast cancer and highlights the promising prospects for the development of circadian rhythm-based interventions to enhance treatment efficacy and improve patient outcomes.

A Cross-Sectional Study of Circadian Stimulus in Swedish Radiographers' Light Environment.

Background: Timely light exposure is a vital aspect to achieve better sleep and well-being. As there are risks with a disturbed circadian rhythm and benefits with light settings that stimulate the rhythm, the circadian effective light, circadian stimulus (CS), for radiographers was examined. Aim: The aim of the study was to compare radiographers' light environment on the workstations, at a university hospital in Southern Sweden in the form of CS and relate that to recommendations published by the Swedish Environmental Protection Agency. Method: A cross-sectional method has been applied. The measurements for CS were collected in all labs in the radiology department in the middle of January. Result: A total of 804 measures were evenly collected resulting in a median for the 19 labs, where the observed median for all labs was 0.091 CS which is significantly lower than the recommended value of 0.3 CS (p < .001). Comparing work light settings with maximum light levels in the brightest and darkest labs showed a significant difference (p < .001). Conclusion: The CS values in the labs, at the radiology department at a university hospital in Southern Sweden, do not reach the recommended values of circadian stimulus published by the Swedish Environmental Protection Agency when the radiographers themselves set the light. There is a potential for improvement as a significant difference could be seen between the chosen level of light and the maximum possible level of light.

Environmental Light Controls the Daily Organization of Breathing by Activating Brn3b-expressing Intrinsically Photosensitive Retinal Ganglion Cells in Mice.

Rhythmic, daily fluctuations in minute ventilation are controlled by the endogenous circadian clock located in the suprachiasmatic nucleus (SCN). While light serves as a potent synchronizer for the SCN, it also influences physiology and behavior by activating Brn3b-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs). It is currently unclear the extent to which the external light environment shapes daily ventilatory patterns independent of the SCN. To determine the relative influence of environmental light versus circadian timing on the organization of daily rhythms in minute ventilation, we used whole-body plethysmography to measure the breathing of mice housed on a non-entraining T28 cycle (14 h light:14 h dark). Using this protocol, we found that minute ventilation exhibits a ~28-h rhythm with a peak at dark onset that coincides with the light:dark cycle and the animals' locomotor activity. To determine if this 28-h rhythm in minute ventilation was mediated by Brn3b-expressing ipRGCs, we measured the breathing of Brn3bDTA mice housed under the T28 cycle. Brn3bDTA mice lack the Brn3b-expressing ipRGCs that project to many non-SCN brain regions. We found that despite rhythmic light cues occurring on a 28-h basis, Brn3bDTA mice exhibited 24-h rhythms in minute ventilation, locomotor activity, and core body temperature consistent with organization by the SCN. The 24-h minute ventilation rhythm of Brn3bDTA mice was found to be driven predominantly by tidal volume rather than respiratory rate. These data indicate that the external light:dark cycle can directly drive daily patterns in minute ventilation by way of Brn3b-expressing ipRGCs. In addition, these data strongly suggest that the activation of Brn3b-expressing ipRGCs principally organizes daily patterns in breathing and locomotor activity when light:dark cues are presented in opposition to endogenous clock timing.

Photoneuroendocrine, circadian and seasonal systems: from photoneuroendocrinology to circadian biology and medicine.

This contribution highlights the scientific development of two intertwined disciplines, photoneuroendocrinology and circadian biology. Photoneuroendocrinology has focused on nonvisual photoreceptors that translate light stimuli into neuroendocrine signals and serve rhythm entrainment. Nonvisual photoreceptors first described in the pineal complex and brain of nonmammalian species are luminance detectors. In the pineal, they control the formation of melatonin, the highly conserved hormone of darkness which is synthesized night by night. Pinealocytes endowed with both photoreceptive and neuroendocrine capacities function as "photoneuroendocrine cells." In adult mammals, nonvisual photoreceptors controlling pineal melatonin biosynthesis and pupillary reflexes are absent from the pineal and brain and occur only in the inner layer of the retina. Encephalic photoreceptors regulate seasonal rhythms, such as the reproductive cycle. They are concentrated in circumventricular organs, the lateral septal organ and the paraventricular organ, and represent cerebrospinal fluid contacting neurons. Nonvisual photoreceptors employ different photopigments such as melanopsin, pinopsin, parapinopsin, neuropsin, and vertebrate ancient opsin. After identification of clock genes and molecular clockwork, circadian biology became cutting-edge research with a focus on rhythm generation. Molecular clockworks tick in every nucleated cell and, as shown in mammals, they drive the expression of more than 3000 genes and are of overall importance for regulation of cell proliferation and metabolism. The mammalian circadian system is hierarchically organized; the central rhythm generator is located in the suprachiasmatic nuclei which entrain peripheral circadian oscillators via multiple neuronal and neuroendocrine pathways. Disrupted molecular clockworks may cause various diseases, and investigations of this interplay will establish a new discipline: circadian medicine.

Chronobiology of Cancers in the Liver and Gut.

Circadian rhythms dictate the timing of cellular and organismal physiology to maintain homeostasis. Within the liver and gut, circadian rhythms influence lipid and glucose homeostasis, xenobiotic metabolism, and nutrient absorption. Disruption of this orchestrated timing is known to negatively impact human health and contribute to disease progression, including carcinogenesis. Dysfunctional core clock timing has been identified in malignant growths and may be used as a molecular signature of disease progression. Likewise, the circadian clock and its downstream effectors also represent potential for novel therapeutic targets. Here, the role of circadian rhythms in the pathogenesis of cancers of the liver and gut will be reviewed, and chronotherapy and chronopharmacology will be explored as potential treatment options.

LIP1 Regulates the Plant Circadian Oscillator by Modulating the Function of the Clock Component GIGANTEA.

Circadian clocks are biochemical timers regulating many physiological and molecular processes according to the day/night cycles. The function of the oscillator relies on negative transcriptional/translational feedback loops operated by the so-called clock genes and the encoded clock proteins. Previously, we identified the small GTPase LIGHT INSENSITIVE PERIOD 1 (LIP1) as a circadian-clock-associated protein that regulates light input to the clock in the model plant Arabidopsis thaliana. We showed that LIP1 is also required for suppressing red and blue light-mediated photomorphogenesis, pavement cell shape determination and tolerance to salt stress. Here, we demonstrate that LIP1 is present in a complex of clock proteins GIGANTEA (GI), ZEITLUPE (ZTL) and TIMING OF CAB 1 (TOC1). LIP1 participates in this complex via GUANINE EX-CHANGE FACTOR 7. Analysis of genetic interactions proved that LIP1 affects the oscillator via modulating the function of GI. We show that LIP1 and GI independently and additively regulate photomorphogenesis and salt stress responses, whereas controlling cell shape and photoperiodic flowering are not shared functions of LIP1 and GI. Collectively, our results suggest that LIP1 affects a specific function of GI, possibly by altering binding of GI to downstream signalling components.

Sex-specific chrono-nutritional patterns and association with body weight in a general population in Spain (GCAT study).

BACKGROUND: Altered meal timing patterns can disrupt the circadian system and affect metabolism. Our aim was to describe sex-specific chrono-nutritional patterns, assess their association with body mass index (BMI) and investigate the role of sleep in this relationship. METHODS: We used the 2018 questionnaire data from the population-based Genomes for Life (GCAT) (n = 7074) cohort of adults aged 40-65 in Catalonia, Spain, for cross-sectional analysis and its follow-up questionnaire data in 2023 (n = 3128) for longitudinal analysis. We conducted multivariate linear regressions to explore the association between mutually adjusted meal-timing variables (time of first meal, number of eating occasions, nighttime fasting duration) and BMI, accounting for sleep duration and quality, and additional relevant confounders including adherence to a Mediterranean diet. Finally, cluster analysis was performed to identify chrono-nutritional patterns, separately for men and women, and sociodemographic and lifestyle characteristics were compared across clusters and analyzed for associations with BMI. RESULTS: In the cross-sectional analysis, a later time of first meal (ß 1 h increase = 0.32, 95% CI 0.18, 0.47) and more eating occasions (only in women, ß 1 more eating occasion = 0.25, 95% CI 0.00, 0.51) were associated with a higher BMI, while longer nighttime fasting duration with a lower BMI (ß 1 h increase=-0.27, 95% CI -0.41, -0.13). These associations were particularly evident in premenopausal women. Longitudinal analyses corroborated the associations with time of first meal and nighttime fasting duration, particularly in men. Finally, we obtained 3 sex-specific clusters, that mostly differed in number of eating occasions and time of first meal. Clusters defined by a late first meal displayed lower education and higher unemployment in men, as well as higher BMI for both sexes. A clear "breakfast skipping" pattern was identified only in the smallest cluster in men. CONCLUSIONS: In a population-based cohort of adults in Catalonia, we found that a later time of first meal was associated with higher BMI, while longer nighttime fasting duration associated with a lower BMI, both in cross-sectional and longitudinal analyses.

Identification of circadian clock-related immunological prognostic index and molecular subtypes in prostate cancer.

BACKGROUND: Evidence suggests that the circadian clock (CIC) is among the important factors for tumorigenesis. We aimed to provide new insights into CIC-mediated molecular subtypes and gene prognostic indexes for prostate cancer (PCa) patients undergoing radical prostatectomy (RP) or radical radiotherapy (RT). METHODS: PCa data from TCGA was analyzed to identify differentially expressed genes (DEGs) with significant fold changes and p-values. A prognostic index called CIC-related gene prognostic index (CICGPI) was developed through clustering methods and survival analysis and validated on multiple data sets. The diagnostic accuracy of CICGPI for resistance to chemotherapy and radiotherapy was confirmed. Additionally, the interaction between tumor immune environment and CICGPI score was explored, along with their correlation with prognosis. RESULTS: TOP2A, APOE, and ALDH2 were used to classify the PCa patients into two subtypes. Cluster 2 had a higher risk of biochemical recurrence (BCR) than cluster 1 for PCa patients undergoing RP or RT. A CIC-related gene prognostic index (CICGPI) was constructed using the above three genes for PCa patents in the TCGA database. The CICGPI score showed good prognostic value in the TCGA database and was externally confirmed by PCa patients in GSE116918, MSKCC2010 and GSE46602. In addition, the CICGPI score had a certain and high diagnostic accuracy for tumor chemoresistance (AUC: 0.781) and radioresistance (AUC: 0.988). For gene set variation analysis, we observed that both beta alanine metabolism and limonene and pinene degradation were upregulated in cluster 1 for PCa patients undergoing RP or RT. For PCa patients undergoing RP, cell cycle, homologous recombination, mismatch repair, and DNA replication were upregulated in cluster 2. A strongly positive relationship between cancer-related fibroblasts and CICGPI score was observed in PCa patients undergoing RP or RT. Moreover, a high density of CAFs was highly closely associated with poorer BCR-free survival of PCa patients. CONCLUSIONS: In this study, we established CIC-related immunological prognostic index and molecular subtypes, which might be useful for the clinical practice.