Circadian Expression Research Articles

Circadian clock does not play an essential role in daylength measurement for growth-phase transition in Marchantia polymorpha.

Daylength is perceived as a seasonal cue to induce growth-phase transition at a proper time of a year. The core of the mechanism of daylength measurement in angiosperms lies in the circadian clock-controlled expression of regulators of growth-phase transition. However, the roles of the circadian clock in daylength measurement in basal land plants remain largely unknown. In this study, we investigated the contribution of circadian clock to daylength measurement in a basal land plant, the liverwort Marchantia polymorpha. In M. polymorpha, transition from vegetative to reproductive phase under long-day conditions results in differentiation of sexual branches called gametangiophores which harbor gametangia. First, we showed that a widely used wild-type accession Takaragaike-1 is an obligate long-day plant with a critical daylength of about 10 hours and requires multiple long days. Then, we compared the timing of gametangiophore formation between wild type and circadian clock mutants in long-day and short-day conditions. Mutations in two clock genes, MpTIMING OF CAB EXPRESSION 1 and MpPSEUDO-RESPONSE REGULATOR, had no significant effects on the timing of gametangiophore formation. In addition, when M. polymorpha plants were treated with a chemical which lengthens circadian period, there was no significant effect on the timing of gametangiophore formation, either. We next observed the timing of gametangiophore formation under various non-24-h light/dark cycles to examine the effect of phase alteration in circadian rhythms. The results suggest that daylength measurement in M. polymorpha is based on the relative amount of light and darkness within a cycle rather than the intrinsic rhythms generated by circadian clock. Our findings suggest that M. polymorpha has a daylength measurement system which is different from that of angiosperms centered on the circadian clock function.

Acute HDM exposure shows time-of-day and sex-based differences in the severity of lung inflammation and circadian clock disruption.

Asthma is a chronic inflammatory disease that shows a time-of-day response to variations in symptoms/severity. However, how the lung circadian clock influences time-of-day response and sex-based differences in house dust mite (HDM)-induced airway inflammation and remodeling has not been thoroughly investigated. We sought to determine whether acute HDM exposure in wild-type mice shows time-of-day response and sex-based differences in allergic airway inflammation and circadian clock disruption in the lungs. Wild-type (C57BL/6J) and Rev-erbα knockout (KO) mice were exposed to either PBS or HDM (for 10 days) intranasally at Zeitgeber time (ZT0: 6 am; ZT12: 6 pm) and euthanized 48 hours after the last exposure. Acute HDM-induced time-of-day response and sex-based differences in lung inflammation, gated cytokines/chemokines, humoral and hormonal responses, and circadian clock gene expression were analyzed. Acute HDM-exposed mice showed a time-of-day response and sex-based differences in exaggerated lung inflammation (inflammatory eosinophils and interstitial macrophages) at ZT12 when compared with ZT0. HDM-exposed female mice showed increased inflammatory response at ZT12, but HDM-exposed male mice showed comparatively lower inflammation with no time-of-day response. HDM-exposed female and male mice showed augmented IgE levels at ZT12 when compared with ZT0. Myeloid innate immunity panel, cytokines/chemokines, and mucin genes showed a time-of-day gating response at ZT0 and ZT12 in the HDM group. In addition, HDM exposure altered the expression of circadian clock genes in the lung, which was evident in female mice at ZT12. Overall, female mice showed significant time-of-day responses to all these parameters compared with male mice. Rev-erbα KO mice exposed to acute HDM showed exaggerated lung inflammation associated with increased IgE and proinflammatory cytokines in bronchoalveolar lavage fluid. Interestingly, HDM exposure causes reduced expression of clock genes in flow-sorted resident eosinophils but not alveolar macrophages. Acute HDM exposure reduced the nocturnal locomotor activity in mice 5 days post-HDM exposure until day10. This study shows a time-of-day response to acute HDM exposure and sex-based differences in the severity of lung inflammation and humoral immune response associated with circadian clock disruption. Our findings support the use of separate female and male mice cohorts for preclinical studies to understand the molecular heterogeneity in asthma pathophysiology.

Acute and Repeated Ozone Exposures Differentially Affect Circadian Clock Gene Expression in Mice (Adv. Biology 11/2023)

Acute and Repeated Ozone Exposures Differentially Affect Circadian Clock Gene Expression in Mice (Adv. Biology 11/2023)

Molecular characterization and dietary regulation of the forkhead box O3 (foxo3a and foxo3b) in grass carp (Ctenopharyngodon idella)

The forkhead box O3 (foxo3) regulates the target genes expression involved in regulating cell cycle and biological metabolism. In the study, foxo3a and foxo3b of grass carp (Ctenopharyngodon idella) were cloned. The foxo3a cDNA have a complete open reading frame (ORF) spanning 1431 bp, which encodes a polypeptide of 476 amino acids. The foxo3b cDNA contains a complete ORF encompassing 1959 bp, encoding a protein consisting of 652 amino acid residues. The analysis of genetic codon preference and phylogenetic relationships revealed that the foxo3a and foxo3b genes in grass carp are closely related to the counterparts of Danio rerio and Megalobrama amblycephala. Tissue expression analysis showed that foxo3a expression reached the maximum in the brain while foxo3b expression in the muscle being the highest. Circadian expression pattern showed that, foxo3a expression presented a periodic upward trend from 3:00–9:00, 12:00–18:00 and 21:00–24:00, and the maximum level of foxo3b was detected at 9:00. Moreover, dietary regulation of foxo3a and foxo3b expression were performed in our research. In the feeding trial with different protein sources, the groups of fishmeal, rapeseed meal and soybean meal are in contrast to each other. Foxo3a expression was significantly higher in fish fed with rapeseed meal compared to those fed with soybean meal and fishmeal at 14th and 21st days of the experiment. Foxo3b expression was highest in the fishmeal group, followed by rapeseed meal, while it was lowest in soybean meal at 14th and 28th days. Analysis of the effect of dietary alanine-glutamine dipeptide on foxo3 expression in grass carp revealed that the expression of foxo3a gradually increased with increasing dietary Ala-Gln dipeptide concentration and reached its highest level at a concentration of 1.5%. Conversely, foxo3b expression significantly decreased when the dipeptide concentration reached 2%. The findings of this study may provide new insights into the molecular properties, spatiotemporal dynamics, and nutritional regulation of foxo3 in fish.

Effects of eyestalk ablation on growth, feeding behavior, movement and circadian gene expression in Haliotis discus hannai

The present study aimed to investigate the effects of eyestalk ablation on growth, feeding behavior, circadian movement activity, and circadian gene expression in the abalone Haliotis discus hannai. Abalones were divided into two groups: eyestalk-ablated (EA) and control (C), and were cultured for 60 days. Results showed that the EA group exhibited significantly higher growth rates in body weight compared to the C group. However, the EA group also had a higher mortality rate, indicating the negative consequences of eyestalk ablation. The feeding rate was significantly higher in the EA group, especially during nocturnal feeding, suggesting that eyestalk ablation may specifically affect nocturnal feeding behavior in abalone. Both EA and C groups displayed rhythmic oscillations in movement activity, with no significant differences in mesor and amplitude. Nevertheless, the peak of populational movement proportion in the EA group occurred approximately 2 h earlier than that in the C group. Transcriptome analysis identified 417 circadian genes, with the most significant enrichment found in the growth-related thyroid hormone signaling pathway. The expression of five core clock genes (clock, cry, rho, tipin, per) exhibited significant circadian rhythms in H. discus hannai, while their rhythmic oscillation significance was weaker in the EA group, except for the tipin transcript. These findings reveal that eyestalk ablation affects growth, feeding and locomotor behavior, and clock gene expression in abalone, providing valuable insights for understanding the circadian regulatory mechanisms and physiological ecological adaptations of abalone. However, due to its harmful effects on animal welfare and the limited promotion of growth, this technology is not advocated for use in aquaculture practices.

Sex and age-dependent characterization of the circadian clock as a potential biomarker for physical performance: A prospective study protocol.

Circadian rhythms (CR) regulate daily cycles in behavior, physiology and molecular processes. CRs are endogenous and vary across individuals. Seasonal changes can influence CR. Accordingly, rhythms with different characteristics (amplitude, phase) are depicted during the summer months, as compared to winter. Increasing evidence points to an influence of circadian regulation on physical performance. Here, we aim to obtain a comprehensive circadian gene expression profile for physically active individuals, which can potentially be used for the identification of optimal time intervals for physical exercise. To explore these different aspects, we propose a study where we will carry out a molecular analysis of CR by measuring the expression of specific clock and clock-controlled genes, based on a non-invasive approach using RNA extracted from saliva in physically active, healthy participants. We will collect data across two seasons and use computational algorithms to integrate the molecular data with hormonal data (cortisol and melatonin), and generate a profile of CR in healthy individuals of different sex and age groups. Finally, we will use computational tools to predict optimal time intervals for physical performance based on the above-described data, thereby retrieving valuable data on the circadian clock as a key factor for health maintenance and optimization.

Exploring the role of mTOR signaling pathway in ketamine's therapeutic effects on suicide risk in depression: Insights into circadian dysregulation mechanisms

Depression is a common psychiatric condition with a substantial number of patients, who fail to achieve response or remission despite index antidepressant treatment. Insomnia and circadian misalignment are established and modifiable suicide risk factors. In recent years suicide rates have significantly increased. Commonly used methods (lithium, clozapine, or dialectical behavioral therapy and cognitive-behavioral therapy) reduce the long-term suicide risk but are inefficient in emergencies. Ketamine is a non-competitive N-methyl-D-aspartate receptor novel agent with rapid-acting antidepressant and anti-suicidal properties. Yet, anti-suicidal effects are only partially mood-dependent, implying other pathways are involved in the reduction of suicidal ideation. Ketamine induces an increase in mammalian target of ramapycin and brain-derived neurotrophic factor expression, influencing circadian dysregulation and stimulating synaptogenesis and restoring the synaptic integrity. In addition, ketamine seems to improve sleep and alter circadian clock gene expression (i.e., Bmal1, CLOCK, PER1, PER2, PER3, Cry 1, Cry 2). Objective estimates in nocturnal electroencephalography show an increase in slow wave sleep, total sleep time and rapid eye movement sleep. It may be hypothesized that ketamine’s anti-suicidal properties stem from the improvement in both sleep and circadian dysregulation. Further studies should investigate the relationship between ketamine, sleep, circadian rhythms and suicidality. The aim of the paper is to put forward a hypothesis about circadian dysregulation in depression and suicidality via ketamine use in mood disorders.

Diurnal circadian clock gene expression is altered in models of genetic and acquired epilepsy.

Growing evidence demonstrates a relationship between epilepsy and the circadian system. However, relatively little is known about circadian function in disease states, such as epilepsy. This study aimed to characterize brain and peripheral core circadian clock gene expression in rat models of genetic and acquired epilepsy. For the Genetic Absence Epilepsy Rats from Strasbourg (GAERS) study, we used 40 GAERS and 40 non-epileptic control (NEC) rats. For the kainic acid status epilepticus (KASE) study, we used 40 KASE and 40 sham rats. Rats were housed in a 7 am:7 pm light-dark cycle. Hypothalamus, hippocampus, liver, and small intestine samples were collected every 3 h throughout the light period. We then assessed core diurnal clock gene expression of per1, cry1, clock, and bmal1. In the GAERS rats, all tissues exhibited significant changes in clock gene expression (P < 0.05) when compared to NEC. In the KASE rats, there were fewer effects of the epileptic condition in the hypothalamus, hippocampus, or small intestine (P > 0.05) compared with shams. These results indicate marked diurnal disruption to core circadian clock gene expression in rats with both generalized and focal chronic epilepsy. This could contribute to epileptic symptomology and implicate the circadian system as a viable target for future treatments.

Genome-Wide Identification of 5-HT Receptor Gene Family in Razor Clam Sinonovacula constricta and Their Circadian Rhythm Expression Analysis.

Serotonin (5-HT) is primarily distributed in the gastrointestinal and central nervous systems, where it plays a crucial role in regulating various physiological functions such as digestion, reproduction and establishing animal emotions. 5-HT is an effective oxytocin widely used in molluscan aquaculture, and its physiological functions are performed by binding to corresponding 5-HT receptors (5-HTRs). In this study, seven 5-HTR genes of Sinonovacula constricta (Sc5-HTRs) were identified and analyzed, and they were designated as Sc5-HT1A, Sc5-HT1D, Sc5-HT2-1, Sc5-HT2-2, Sc5-HT2-3, Sc5-HT4 and Sc5-HT6. Phylogenetic analysis showed that the seven Sc5-HTRs were conserved among mollusks, and the Sc5-HTRs were all transmembrane proteins. The seven Sc5-HTR genes were distributed on chromosome 1, 2, 13 and 14. After injecting 5-HT, there was a significant increase in mRNA expression levels of Sc5-HT1A (p < 0.05) and Sc5-HT2-3 (p < 0.01), while Sc5-HT4 decreased significantly (p < 0.01) compared to control groups which might be effective 5-HT receptors. Furthermore, two of the receptors (Sc5-HT2-3 and Sc5-HT4) were expressed in the circadian rhythm patterns, indicating their potential influence on the nocturnal spawning of S. constricta. Overall, these findings provide a theoretical basis for understanding the structures and functions of 5-HTR gene family members, and may facilitate the artificial propagation of mollusks.

CRH-R2 signalling modulates feeding and circadian gene expression in hypothalamic mHypoA-2/30 neurons.

The hypothalamic type 2 corticotropin releasing hormone receptor (CRH-R2) plays critical roles in homeostatic regulation, particularly in fine tuning stress recovery. During acute stress, the CRH-R2 ligands CRH and urocortins promote adaptive responses and feeding inhibition. However, in rodent models of chronic stress, over-exposure of hypothalamic CRH-R2 to its cognate agonists is associated with urocortin 2 (Ucn2) resistance; attenuated cAMP-response element binding protein (CREB) phosphorylation and increased food intake. The molecular mechanisms involved in these altered CRH-R2 signalling responses are not well described. In the present study, we used the adult mouse hypothalamus-derived cell line mHypoA-2/30 to investigate CRH-R2 signalling characteristics focusing on gene expression of molecules involved in feeding and circadian regulation given the role of clock genes in metabolic control. We identified functional CRH-R2 receptors expressed in mHypoA-2/30 cells that differentially regulate CREB and AMP-activated protein kinase (AMPK) phosphorylation and downstream expression of the appetite-regulatory genes proopiomelanocortin (Pomc) and neuropeptide Y (Npy) in accordance with an anorexigenic effect. We studied for the first time the effects of Ucn2 on clock genes in native and in a circadian bioluminescence reporter expressing mHypoA-2/30 cells, detecting enhancing effects of Ucn2 on mRNA levels and rhythm amplitude of the circadian regulator Aryl hydrocarbon receptor nuclear translocator-like protein 1 (Bmal1), which could facilitate anorexic responses in the activity circadian phase. These data uncover novel aspects of CRH-R2 hypothalamic signalling that might be important in regulation of circadian feeding during stress responses.

The Relationship between Clock Genes, Sirtuin 1, and Mitochondrial Activity in Head and Neck Squamous Cell Cancer: Effects of Melatonin Treatment.

The circadian clock is a regulatory system, with a periodicity of approximately 24 h, which generates rhythmic changes in many physiological processes, including mitochondrial activity. Increasing evidence links chronodisruption with aberrant functionality in clock gene expression, resulting in multiple diseases such as cancer. Melatonin, whose production and secretion oscillates according to the light-dark cycle, is the principal regulator of clock gene expression. In addition, the oncostatic effects of melatonin correlate with an increase in mitochondrial activity. However, the direct links between circadian clock gene expression, mitochondrial activity, and the antiproliferative effects of melatonin in cancers, including head and neck squamous cell carcinoma (HNSCC), remain largely unknown. In this study, we analyzed the effects of melatonin on HNSCC cell lines (Cal-27 and SCC9), which were treated with 500 and 1000 µM melatonin. We found that the antiproliferative effect of melatonin is not mediated by the Bmal1 clock gene. Additionally, high doses of melatonin were observed to result in resynchronization of oscillatory circadian rhythm genes (Per2 and Sirt1). Surprisingly, the resynchronizing effect of melatonin on Per2 and Sirt1 did not produce alterations in the oscillation of mitochondrial respiratory activity. These results increase our understanding of the possible antiproliferative mechanisms in melatonin in the treatment of head and neck squamous cell carcinoma and suggest that its antiproliferative effects are independent of clock genes but are directly related to mitochondrial activity.

Synechococcus elongatus Argonaute reduces natural transformation efficiency and provides immunity against exogenous plasmids.

S. elongatus is an important cyanobacterial model organism for the study of its prokaryotic circadian clock, photosynthesis, and other biological processes. It is also widely used for genetic engineering to produce renewable biochemicals. Our findings reveal an SeAgo-based defense mechanism in S. elongatus against the horizontal transfer of genetic material. We demonstrate that deletion of the ago gene facilitates genetic studies and genetic engineering of S. elongatus.

Bioinformatics Integrative Analysis of Circadian Rhythms Effects on Atopic Dermatitis and Dendritic Cells.

Atopic dermatitis (AD) is an allergic inflammatory skin disease caused by aberrant and over-reactive immune response. Although circadian rhythm disruption is implicated in multiple immunoinflammatory conditions, including AD, the mechanisms at the molecular level underlying AD and circadian rhythms remain elusive. Bulk and single-cell RNA-sequencing data of AD patients were acquired from the Gene Expression Omnibus, including GSE121212, GSE120721, and GSE153760 datasets. A single-sample gene set enrichment analysis was performed to estimate circadian rhythm gene expression levels. A differential expression analysis was utilized to identify the key candidate genes in AD. CIBERSORT was used to quantify the proportions of immune cells, and the R package "Seurat" was utilized to investigate single-cell RNA-sequencing data. Circadian rhythm gene expression levels were lower in AD skin samples than in normal skin samples. Dendritic cells were significantly upregulated and negatively correlated with circadian rhythm gene expression levels in AD patients. Compared with circadian rhythm-related genes in the control samples, ARNTL2, NOCT, and RORC were differentially expressed in AD; ARNTL2 and NOCT were significantly upregulated, whereas RORC was significantly downregulated in AD. ARNTL2, NOCT, and RORC also showed robust abilities to diagnose AD. We validated that the abundance of the dendritic cell was positively correlated with the ARNTL2 and NOCT expression levels using bulk RNA-sequencing data of the GSE121212 and single-cell RNA-sequencing data of the GSE153760. Moreover, the functional enrichment analysis showed that the IL-17 and NF-κB signaling pathways, Th1 and Th2 cell differentiations, and primary immunodeficiency, were enriched in AD patients. The findings of this study suggested that the circadian rhythm is involved in the progression of AD, and RNTL2, NOCT, and RORC as well as dendritic cells are differentially expressed in AD. These findings could be used to introduce diagnostic and chronotherapeutic modalities for AD.

Glucose restriction induces AMPK-SIRT1-mediated circadian clock gene Per expression and delays NSCLC progression

The rhythmic expression of the circadian clock is intimately linked to the health status of the body. Disturbed circadian clock rhythms might lead to a wide range of metabolic diseases and even cancers. Our previous study showed that glucose restriction was able to inhibit non-small cell lung cancer (NSCLC). In the current study, we found that glucose restriction enhanced apoptosis and cell growth delay in NSCLC cells. In addition, we used GEPIA database analysis to derive different effects of each circadian clock gene on lung cancer tissue. Among these circadian clock genes, Per (Period) is lowly expressed in cancer tissues and highly expressed in normal tissues. Moreover, the higher expression of Per in cancer patients has a better prognostic significance. Furthermore, we revealed that glucose restriction induced the expression of the circadian clock gene Per in NSCLC cells by upregulating SIRT1 (Sirtuin1) via activation of the energy response factor AMPK (AMP-activated protein kinase). Changes in Per expression following upregulation or downregulation of AMPK were consistent with AMPK expression. Additionally, a low-carbohydrate ketogenic diet significantly delayed tumor progression in a xenograft tumor model of severe combined immunodeficiency (SCID) mice. Meanwhile, the ketogenic diet increased the expression of AMPK, SIRT1 and Per in vivo. Besides, the ketogenic diet was found to restore the normal rhythmic level of Per by Zeitgeber Time (ZT) experiments. Taken these together, these results indicated a novel mechanism that glucose restriction induces AMPK-SIRT1 mediated circadian clock gene Per expression and delays NSCLC progression, which provided more evidence for glucose restriction as an adjuvant clinical therapeutic strategy in NSCLC.

The effect of voluntary exercise on light cycle stress-induced metabolic resistance.

Disruption of circadian genes affects metabolic homeostasis. Regular exercise programs prevent metabolic dysfunction and alter circadian gene expression In this study, we investigated whether exercise affects light stress-induced circadian rhythm derangement and metabolic resistance. A circadian rhythm derangement mouse model was designed by extending the light exposure by two hours (14 L/10 D) for three weeks. Nine-weekold male mice were single-caged and divided into four groups: sedentary groups with or without light stress, and voluntary wheel-trained groups with or without light stress. In addition, differentiated myotubes were cultured in the presence of dexamethasone with or without 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR). The comprehensive laboratory animal monitoring system was used to analyze the metabolic changes in mice. Moreover, reverse transcription-polymerase chain reaction (RT-PCR) was used to quantify the mRNA expression levels of circadian genes in animal and cell culture models. Three weeks of light stress reduced the running distance and increased the weight of mice. In addition, VO2 consumption and heat production were increased during the night cycle under non-stress conditions but not under stress conditions. PCR analysis revealed that exercise and stress altered the expression levels of circadian genes in the hypothalamus and quadriceps muscles. mRNA expression levels of period circadian regulator 1 were downregulated in the quadriceps muscles of the stressed sedentary group compared to that in muscles of the non-stressed sedentary group. Furthermore, differentiated myotube cells cultured in the presence of dexamethasone, with or without AICAR, showed distinct oscillation patterns at various time points. Our study demonstrates that exercise partially prevents metabolic disruption by regulating the circadian gene expression in skeletal muscles.

Circadian disruption does not alter tumorigenesis in a mouse model of lymphoma.

Background: Disruption of natural light cycles, as experienced by shift workers, is linked to enhanced cancer incidence. Several mouse models of cancer develop more severe disease when exposed to irregular light/dark cycles, supporting the connection between circadian disruption and increased cancer risk. Cryptochrome 2 (CRY2), a repressive component of the molecular circadian clock, facilitates turnover of the oncoprotein c-MYC, one mechanism that may link the molecular clock to tumorigenesis. In Eμ-MYC mice, which express transgenic c-MYC in B cells and develop aggressive lymphomas and leukemia, global Cry2 deletion reduces survival and enhances tumor formation. Lighting conditions that mimic the disruption experienced by shift workers dampen Cry2 transcripts in peripheral tissues of C57BL/6J mice. Although it is milder than homozygous deletion of Cry2, we hypothesized that reduced Cry2 rhythmicity could alter MYC protein accumulation and contribute to enhanced cancer risk caused by circadian disruption. We tested this hypothesis in MYC-driven lymphoma. Methods: We housed Eμ-MYC mice in light-tight boxes set to either control (continuous cycles of 12-hours of light followed by 12-hours of dark, LD12:12) or chronic jetlag (eight-hour light phase advances every two to three days, CJL) lighting conditions and assessed the impact of disrupted light cycles on survival and tumor formation in Eμ-MYC mice. Results: Environmental disruption of circadian rhythms did not alter tumor location, tumor growth, or survival in Eμ-MYC mice. Conclusions: Dampened rhythms of Cry2 following disruption of circadian light exposures is milder than deletion of Cry2. The lack of phenotype caused by altered circadian gene expression in contrast to enhanced tumorigenesis caused by homozygous deletion of Cry2 suggests that CRY2 dosage impacts this model. Importantly, these findings indicate that increased cancer risk associated with circadian disruption arises from one or more mechanisms that are not recapitulated here, and may be different in distinct tumor types.

The Circadian Nobiletin-ROR Axis Suppresses Adipogenic Differentiation and IκBα/NF-κB Signaling in Adipocytes.

Obesity is a known risk factor for metabolic diseases and is often associated with chronic inflammation in adipose tissue. We previously identified the polyethoxylated flavonoid Nobiletin (NOB) as a circadian clock modulator that directly binds to and activates the ROR receptors in the core oscillator, markedly improving metabolic fitness in obese mice. Here, we show that NOB enhanced the oscillation of core clock genes in differentiated 3T3-L1 adipocytes, including ROR target genes such as Bmal1, Cry1, Dec1, and Dec2. NOB inhibited lipid accumulation in 3T3-L1 and SVF cells, concomitant with the dysregulated circadian expression of adipogenic differentiation-related genes including Cebpb, Pparg, Lpl, Scd1, and Fas. Importantly, RORα/RORγ double knockdown in 3T3-L1 cells (Ror DKD) significantly attenuated the effects of NOB on circadian gene expression and lipid accumulation. Furthermore, whereas NOB upregulated the expression of IκBα, a target of RORs, to inhibit NF-κB activation and proinflammatory cytokine expression, Ror DKD cells exhibited a heightened activation of the NF-κB pathway, further indicating a requisite role of RORs for NOB efficacy in adipocytes. Together, these results highlight a significant regulatory function of the NOB-ROR axis in the circadian expression of clock and clock-controlled genes in adipocytes, thereby governing adipogenic differentiation, lipogenesis, and inflammation.

Reanalysis of primate brain circadian transcriptomics reveals connectivity-related oscillations

Research shows that brain circuits controlling vital physiological processes are closely linked with endogenous time-keeping systems. In this study, we aimed to examine oscillatory gene expression patterns of well-characterized neuronal circuits by reanalyzing publicly available transcriptomic data from a spatiotemporal gene expression atlas of a non-human primate. Unexpectedly, brain structures known for regulating circadian processes (e.g., hypothalamic nuclei) did not exhibit robust cycling expression. In contrast, basal ganglia nuclei, not typically associated with circadian physiology, displayed the most dynamic cycling behavior of its genes marked by sharp temporally defined expression peaks. Intriguingly, the mammillary bodies, considered hypothalamic nuclei, exhibited gene expression patterns resembling the basal ganglia, prompting reevaluation of their classification. Our results emphasize the potential for high throughput circadian gene expression analysis to deepen our understanding of the functional synchronization across brain structures that influence physiological processes and resulting complex behaviors.

Skeletal Muscle Circadian Gene Expression And Physical Function In Older Rats Following Exercise And/or Probiotics

Skeletal Muscle Circadian Gene Expression And Physical Function In Older Rats Following Exercise And/or Probiotics

The WD40 domain-containing protein Ehd5 positively regulates flowering in rice (Oryza sativa).

Heading date (flowering time), which greatly influences regional and seasonal adaptability in rice (Oryza sativa), is regulated by many genes in different photoperiod pathways. Here, we characterized a heading date gene, Early heading date 5 (Ehd5), using a modified bulked segregant analysis method. The ehd5 mutant showed late flowering under both short-day and long-day conditions, as well as reduced yield, compared to the wild type. Ehd5, which encodes a WD40 domain-containing protein, is induced by light and follows a circadian rhythm expression pattern. Transcriptome analysis revealed that Ehd5 acts upstream of the flowering genes Early heading date 1 (Ehd1), RICE FLOWERING LOCUS T 1 (RFT1), and Heading date 3a (Hd3a). Functional analysis showed that Ehd5 directly interacts with Rice outermost cell-specific gene 4 (Roc4) and Grain number, plant height, and heading date 8 (Ghd8), which might affect the formation of Ghd7-Ghd8 complexes, resulting in increased expression of Ehd1, Hd3a and RFT1. Taken together, these results demonstrate that Ehd5 functions as a positive regulator of rice flowering and provide insight into the molecular mechanisms underlying heading date.