Clock Genes

Nursing in the rabbit is under circadian control, and pups have a daily anticipatory behavioral arousal synchronized to this unique event, but it is not known which signal is the main entraining cue. In the present study, we hypothesized that food is the main entraining signal. Using mother‐deprived pups, we tested the effects of artificial feeding on the synchronization of locomotor behavior, plasma glucose, corticosterone, c‐Fos (FOS) and PERIOD1 (PER1) rhythms in suprachiasmatic, supraoptic, paraventricular and tuberomammillary nuclei. At postnatal day 1, an intragastric tube was placed by gastrostomy. The next day and for the rest of the experiment, pups were fed with a milk formula through the cannula at either 02:00 h or 10:00 h [feeding time = zeitgeber time (ZT)0]. At postnatal days 5–7, pups exhibited behavioral arousal, with a significant increase in locomotor behavior 60 min before feeding. Glucose levels increased after feeding, peaking at ZT4–ZT12 and then declining. Co...

The duration of daytime light phase (photoperiod) controls reproduction in seasonal mammals. Syrian hamsters are sexually active when exposed to long photoperiod, while gonadal atrophy is observed after exposure to short photoperiod. The photorefractory period, or photorefractoriness, is a particular state of spontaneous recrudescence of sexual activity that occurs after a long‐term exposure to short photoperiod. Expression of core clock genes in the master circadian clock contained in the suprachiasmatic nuclei depends on photoperiodic conditions. Interestingly, the expression of the Clock gene is also modified in photorefractory Syrian hamsters. Since melatonin and testosterone levels in seasonal species are dependent on photoperiod, photoperiodic variations of Clock mRNA levels in the suprachiasmatic clock could be a consequence of these hormonal changes. To test this hypothesis, we analysed the effects of pinealectomy on Clock mRNA changes due to long to short photoperiod transi...

Chronosomnobulia denotes a behavioral construct defined by the executive regulation of sleep initiation timing in alignment with endogenous circadian rhythms. While sleep hygiene frameworks address a broad range of behaviors influencing sleep quality, they do not isolate the deliberate determination of sleep onset as a distinct executive function. This paper proposes chronosomnobulia as a narrowly defined subcomponent of behavioral self-regulation, emphasizing top-down modulation of sleep initiation timing independent of fluctuating affective or environmental stimuli. In its second iteration, the construct is further grounded in Spinoza's concept of conatus-the organism's immanent striving to persist in its own being-as the ontological basis for understanding why temporal self-regulation is not merely a behavioral option but an expression of the organism's drive toward functional coherence. The relevance of adequate ideation as an activating condition for this drive is explored in the context of post-transplant adherence challenges, where circadian disorganization and identity rupture are identified as conditions of affective passivity that chronosomnobulia, supported by appropriate clinical encounter, may help address. The construct is positioned within behavioral chronobiology and framed descriptively rather than therapeutically. Its relevance may extend to contexts in which circadian stability is vulnerable; however, no claims of clinical efficacy are advanced. Chronosomnobulia presupposes intact executive functioning and is not conceptualized as universally applicable. By delineating this specific regulatory capacity, the present work seeks to clarify a conceptual gap in discussions of sleeprelated behavioral control.

Rancangan produk hot kitchen dalam pelaksanaan pop-up dinner "Brontëa Dining: Jurassic World Experience" merupakan sebuah studi yang berfokus pada pengembangan hidangan kuliner berbasis pengalaman (experiential dining) dengan konsep fine dining tematik. Kegiatan ini mengangkat tema prasejarah "Jurassic" yang mengintegrasikan unsur visual, sensori, dan kreativitas dalam penyajian makanan untuk meningkatkan daya tarik dan kepuasan konsumen. Permasalahan utama dalam studi ini adalah bagaimana merancang menu hot kitchen yang tidak hanya menarik secara visual dan sesuai tema, tetapi juga memiliki kualitas rasa tinggi serta layak secara teknis dan finansial. Tujuan penelitian ini adalah menghasilkan produk hidangan panas (soup dan main course) yang inovatif, berkualitas, serta memenuhi aspek sensori, teknis produksi, dan kelayakan ekonomi. Metode yang digunakan meliputi pendekatan deskriptif dengan tahapan pemilihan menu secara sistematis berdasarkan kesesuaian tema, aspek sensori (rasa, tekstur, aroma, dan tampilan), teknik produksi, ketersediaan bahan baku, serta analisis food cost dan Harga Pokok Penjualan (HPP). Hasil studi menunjukkan bahwa terpilih tiga menu utama hot kitchen, yaitu Mushroom Broth sebagai soup, Chilean Sea Bass sebagai first main course, dan Chicken Mousse sebagai second main course, yang dinilai mampu memenuhi seluruh kriteria tersebut. Selain itu, perhitungan biaya menunjukkan bahwa setiap menu memiliki harga jual yang kompetitif dan berpotensi menghasilkan keuntungan. Kesimpulannya, rancangan produk ini berhasil menghasilkan konsep menu yang inovatif, layak secara operasional dan finansial, serta mampu memberikan pengalaman kuliner yang unik dan berkesan bagi konsumen.

Kegiatan pop-up dinner bertajuk "Jurassic" merupakan proyek akhir mahasiswa Semester 6B Program Studi Seni Kuliner Politeknik Pariwisata Palembang yang mengusung konsep fine dining tematik. Studi ini bertujuan untuk mengintegrasikan keterampilan teknis kuliner dengan kemampuan bisnis kreatif, sekaligus memperkenalkan konsep makan malam eksklusif yang edukatif dan interaktif kepada masyarakat Palembang. Permasalahan utama yang diangkat adalah bagaimana menciptakan pengalaman bersantap yang tidak monoton melalui perpaduan narasi prasejarah dan inovasi kuliner. Metode pelaksanaan dilakukan melalui simulasi operasional restoran lengkap, mulai dari perencanaan tema, penyusunan struktur organisasi, hingga pengembangan menu nusantara yang dimodifikasi secara modern. Temuan utama dari perencanaan ini adalah terciptanya rangkaian hidangan teatrikal, seperti "The Asteroid Impact" dan "The Volcanic Ash", yang menggunakan teknik memasak modern seperti sous-vide dan penggunaan bahan unik seperti activated charcoal untuk mendukung visualisasi tema. Sebagai kesimpulan, kegiatan ini berhasil merancang sebuah model bisnis kuliner yang tidak hanya menonjolkan aspek rasa, tetapi juga memberikan nilai hiburan dan petualangan bagi 100 target tamu melalui implementasi konsep branding yang kreatif dan instagramable.

While the American horseshoe crab, Limulus polyphemus, has robust circadian and circatidal rhythms, virtually nothing is known about the molecular basis of these rhythms in this species or any other chelicerate. In this study, next generation sequencing was used to assemble transcriptomic reads and then putative homologs of known core and accessory circadian genes were identified in these databases. Homologous transcripts were discovered for one circadian clock input gene, five core genes, 22 accessory genes, and two possible output pathways. Alignments and functional domain analyses showed generally high conservation between the putative L. polyphemus clock genes and homologs from Drosophila melanogaster and Daphnia pulex. The presence of both cry1 and cry2 in the L. polyphemus transcriptome would classify its system as an "ancestral", type 2 clock system. In addition, a novel duplication of CYCLE, and a novel triplication of PERIOD were found. Investigations are currently underway to determine if any of these "circadian" genes also participate in the molecular processes that drive the Limulus circatidal clock.

Cactophilic Drosophila ßies are excellent models to study adaptation to a relatively narrow spectrum of potential host plants and host-driven evolutionary diversiÞcation. Previous studies suggested a complex genetic architecture of wing and male genital morphology in phylogenetically basal species of the D. buzzatii cluster. In this work, we investigate the effect of experimental hybridization and host plant shifts on male genital and wing morphology in D. gouveai Tidon-Sklorz and Sene and D. antonietae Tidon-Sklorz and Sene, a pair of more recently derived species. We explicitly tested the hypotheses that wing and male genital morphology in interspeciÞc hybrids depend on the host plant in which ßies were grown. Our study shows that cactus hosts exert a strong effect on genital and wing morphology and that hybrids can be clearly differentiated on the basis of wing and genital morphology from both parental species. However, the extent of morphological differentiation between hybrids and pure species as well as plasticity patterns varied across organs, suggesting a complex genetic architecture for the studied traits.

Altered functioning of the biological clock is involved in cancer onset and progression. MicroRNAs (miRNAs) interact with the clock genes modulating the function of genetically encoded molecular clockworks. Collaborative interactions may take place within the coding-noncoding RNA regulatory networks. We aimed to evaluate the cross-talk among miRNAs and clock genes in colorectal cancer (CRC). We performed an integrative analysis of miRNA-miRNA and miRNA-mRNA interactions on high-throughput molecular profiling of matched human CRC tissue and non-tumor mucosa, pinpointing core clock genes and their targeting miRNAs. Data obtained in silico were validated in CRC patients and human colon cancer cell lines. In silico we found severe alterations of clock gene-related coding-noncoding RNA regulatory networks in tumor tissues, which were later corroborated by the analysis of human CRC specimens and experiments performed in vitro. In conclusion, specific miRNAs target and regulate the transcription/translation of clock genes and clock gene-related miRNA-miRNA as well as mRNA-miRNA interactions are altered in colorectal cancer. Exploration of the interplay between specific miRNAs and genes, which are critically involved in the functioning of the biological clock, provides a better understanding of the importance of the miRNA-clock genes axis and its derangement in colorectal cancer.

Perineurální sítě jsou strukturou extracelulární matrix centrálního nervového systému, obepínající některé subpopulace neuronů. Jejich vznik souvisí s uzavřením kritické periody a výrazným omezením plasticity. Ve zdravém organismu jsou perineurální sítě důležité pro stabilizaci zralého nervového systému, podporu vysoce aktivních neuronů a jejich ochranu. Při patologických stavech jsou však jedním z faktorů, které zabraňují správné obnově tkáně prostřednictvím tvorby gliové jizvy a zvýšením koncentrace látek s inhibičním efektem na růst neuronů. Rozrušením perineurálních sítí, například enzymaticky, je možné znovu otevřít kritickou periodu a obnovit plasticitu centrálního nervového systému. To vede k potenciaci růstu a větvení neuronů a celkové regeneraci centrálního nervového systému jak po mechanickém poškození, jako je například poranění míchy, tak při neurodegenerativních onemocněních, jako je Alzheimerova choroba. V Alzheimerově chorobě ovlivňují perineurální sítě stejně jako ve...

The study aimed to explore the influence of methylation levels of two clock genes, Bmal1 and Clock, and the association between gene expression and miRNA molecules (miRNA155 and miRNA211) in bipolar disorder. The study sample contains 40 kids whose ages ranged from 2 to 12 years with bipolar disorders, and 20 healthy kids as a control group. The study axes were divided into three parts. The first part involved determining the levels of gene expression for the Bmal1 and Clock genes using qRT-PCR. The second part is the determination of the levels of miRNA and snoRNA molecules that regulate Bmal1 and Clock genes using qRT-PCR. Third part: measuring methylation levels in the promoters of Bmal1 and clock genes using PCR. The results showed a significant decrease in the Bmal1 gene expression; it was the value of folding expression Bmal1 gene = 0.73, and a significant increase in the Clock gene; it was the value of folding expression Clock gene = 1.23. and the results showed a significant increase in miRNA gene expression; the value of folding expression for miRNA155/Bmal1 = 1.76, and a significant decrease in miRNA gene expression; the value of folding expression for miRNA211/Clock = 0.26. while the gene expression level for snoRNA molecule = 1.76 compared with control = 1. Conclusion: The results of this study demonstrate increases in the gene expression folding of the Clock gene and a significant decrease in miRNA211 gene expression which regulates the Clock gene.

The importance of circadian biology has rarely been considered in pre-clinical studies, and even more when translating to the bedside. Circadian biology is becoming a critical factor for improving drug efficacy and diminishing drug toxicity. Indeed, there is emerging evidence showing that some drugs are more effective at nighttime than daytime, whereas for others it is the opposite. This suggests that the biology of the target cell will determine how an organ will respond to a drug at a specific time of the day, thus modulating pharmacodynamics. Thus, it is now time that circadian factors become an integral part of translational research.

Throughout gestation, the close relationship between mothers and their progeny ensures adequate development and a successful transition to postnatal life. By living inside the maternal compartment, the fetus is inevitably exposed to rhythms of the maternal internal milieu such as temperature; rhythms originated by maternal food intake and maternal melatonin, one of the few maternal hormones that cross the placenta unaltered. The fetus, immature by adult standards, is however perfectly fit to accomplish the dual functions of living in the uterine environment and developing the necessary tools to ''mature'' for the next step, i.e. to be a competent newborn. In the fetal physiological context, organ function differs from the same organ's function in the newborn and adult. This may also extend to the developing circadian system. The information reviewed here suggests that the fetal circadian system is organized differently from that of the adult. Moreover, the fetal circadian rhythm is not just present simply as the initial immature expression of a mechanism that has function in the postnatal animal only. We propose that the fetal suprachiasmatic nucleus (SCN) of the hypothalamus and fetal organs are peripheral maternal circadian oscillators, entrained by different maternal signals. Conceptually, the arrangement produces internal temporal order during fetal life, inside the maternal compartment. Following birth, it will allow for postnatal integration of the scattered fetal circadian clocks into an adult-like circadian system commanded by the SCN.

Diabetes mellitus type 2 is a long-standing metabolic disorder that is exemplify by high blood sugar, insulin resistance, and comparative lack of insulin. General symptoms include increased thirst, frequent urination, and unsolved weight loss. Type 2 diabetes is mainly due to obesity and not sufficient work out in public who are heritably prone.Circadian clocks are significant to keep the moment in the sequence of physiological practice, series of behaviour and metabolism. The plasma level of glucose and numerous hormones implicated in glucose homeostasis for example insulin and glucagon exhibit circadian variation. Circadian desynchrony, a feature of alter occupation elevated-fat diet feed and sleep distraction in individual have been linked with metabolic disorders for instance obesity and type 2 diabetes. Circadian rhythm distraction can cause different fitness disarray. Current reading has discovered a seal connection among the pathophysiology of metabolic condition, which is ...

Background: Sleep is an active and complex behavior, yet it has two straightforward properties-timing and duration. Clock genes are associated with dysfunctional timing of sleep, mood, and obesity disorders, which are commonly associated with sleep duration. Sleep duration was assessed in Central Europe, Estonia, and South Tyrol (n Ϸ 77,000) with the Munich ChronoType Questionnaire. It showed a Gaussian distribution in all investigated populations after averaging over a standard workweek and normalization according to age and gender. A follow-up, two-stage design, linkage disequilibrium-based association study was conducted with subjects from South Tyrol (discovery sample; n ϭ 283) and with short (Ͻ 7 hours) and long (Ͼ 8.5 hours) sleepers from Estonia (confirmation sample; n ϭ 1011). One hundred ninety-four single nucleotide polymorphism markers covering 19 candidate clock genes were genotyped in the discovery sample, and two of the best association signals (analyzed by a linear regression model) were investigated in the confirmation sample. Results: Single and multi-marker associations were found within a CLOCK gene intronic region (rs12649507 and rs11932595). In a meta-analysis between South Tyrol and Estonia association signals, rs12649507 (p ϭ .0087) remained significant. Significance persisted only for the multiple-marker association signal of the rs12649507/rs11932595 haplotype GGAA with long sleep (p ϭ .0015). We report an association between variants of the human CLOCK gene and sleep duration in two independent populations. This adds another putative function for CLOCK besides its possible involvement in circadian timing, depression, obesity, and personality.

Circadian rhythms, governed by the dominant central clock, in addition to various peripheral clocks, regulate almost all biological processes, including sleep-wake cycles, hormone secretion and metabolism. In certain contexts, the regulation and function of the peripheral oscillations can be decoupled from the central clock. However, the specific mechanisms underlying muscle-intrinsic clock-dependent modulation of muscle function and metabolism remain unclear. We investigated the outcome of perturbations of the primary and secondary feedback loops of the molecular clock in skeletal muscle by specific gene ablation of Period circadian regulator 2 (Per2) and RAR-related orphan receptor alpha (Rorα), respectively. In both models, a dampening of core clock gene oscillation was observed, while the phase was preserved. Moreover, both loops seem to be involved in the homeostasis of amine groups. Highly divergent outcomes were seen for overall muscle gene expression, primarily affecting circadian rhythmicity in the PER2 knockouts and non-oscillating genes in the RORα knockouts, leading to distinct outcomes in terms of metabolome and phenotype. These results highlight the entanglement of the molecular clock and muscle plasticity and allude to specific functions of different clock components, i.e. the primary and secondary feedback loops, in this context. The reciprocal interaction between muscle contractility and circadian clocks might therefore be instrumental to determining a finely tuned adaptation of muscle tissue to perturbations in health and disease. KEY POINTS: Specific perturbations of the primary and secondary feedback loop of the molecular clock result in specific outcomes on muscle metabolism and function. Ablation of Per2 (primary loop) or Rorα (secondary loop) blunts the amplitude of core clock genes, in absence of a shift in phase. Perturbation of the primary feedback loop by deletion of PER2 primarily affects muscle gene oscillation. Knockout of RORα and the ensuing modulation of the secondary loop results in the aberrant expression of a large number of non-clock genes and proteins. The deletion of PER2 and RORα affects muscle metabolism and contractile function in a circadian manner, highlighting the central role of the molecular clock in modulating muscle plasticity.

Metabolic syndrome and cardiovascular disease are strongly associated with obstructive sleep apnea syndrome (OSAS), which causes substantial changes to normal circadian physiological functions, including metabolic pathways. Because core clock genes are known to be modulated by sleep/vigilance cycles, we asked whether the expression level of mRNA coding for clock genes is altered in non-treated OSAS patients and if it can be corrected by standard continuous positive airway pressure (CPAP) treatment. Peripheral blood was collected from male patients diagnosed with severe OSAS (apnea-hypopnea index ≥ 30/h) before and after treatment initiation. qPCR was used to measure mRNA levels of genes associated with the central circadian pacemaker including CLOCK, BMAL1, Cry1, Cry2, and three Period genes (Per 1, 2, 3) in peripheral blood mononuclear cells (PBMCs). We found statistically significant differences for CLOCK (p-value = 0.022) expression in PBMCs of OSAS patients which were not revert...

Rationale Alcohol consumption shows circadian rhythmicity, i.e., alcohol preference and intake change with circadian time. Circadian rhythmicity is controlled by a biological clock, which has been shown to govern behavioral, physiological, and hormonal processes in synchronization with internal as well as external cues. Molecular components of the clock include circadian clock genes such as period (Per) 1, 2, and 3. Previously, our lab demonstrated the involvement of mouse Per1 (mPer1) and Per2 (mPer2) in modulating cocaine sensitization and reward. What is more, we investigated voluntary alcohol consumption in Per2 Brdm1 mice with the results suggesting a relationship between this circadian clock gene and ethanol consumption. Objective To further complement the mPer2 study, our lab proceeded to assess mPer1's possible role on alcohol intake using operant and free choice two bottle paradigms. Methods Using operant conditions, Per1 Brdm1 and wild type mice were trained to self-administer ethanol (10%) under a fixed ratio 1 (FR1) paradigm. This was ensued by a progressive ratio (PR) schedule. Furthermore, extinction sessions were introduced, followed by reinstatement mea-sures of ethanol-seeking behavior. In another set of animals, the mice were exposed to voluntary long-term alcohol consumption, ensued by a 2-month deprivation phase, after which the alcohol deprivation effect (ADE) was measured. Results Mutant mice did not display a significantly divergent number of reinforced lever presses (FR1 and PR) than wild type animals. Furthermore, no significant differences between groups were obtained regarding reinstatement of ethanol-seeking behavior. Similar results were obtained in the two bottle free choice paradigm. Specifically, no genotype differences concerning consumption and preference were observed over a broad range of different ethanol concentrations. Moreover, after the deprivation phase, both groups exhibited significant ADEs, yet no genotype differences. Conclusions Contrary to the mPer2 data, the present findings do not suggest a relationship between the circadian clock gene mPer1 and ethanol reinforcement, seeking, and relapse behavior.

The importance of circadian biology has rarely been considered in pre-clinical studies, and even more when translating to the bedside. Circadian biology is becoming a critical factor for improving drug efficacy and diminishing drug toxicity. Indeed, there is emerging evidence showing that some drugs are more effective at nighttime than daytime, whereas for others it is the opposite. This suggests that the biology of the target cell will determine how an organ will respond to a drug at a specific time of the day, thus modulating pharmacodynamics. Thus, it is now time that circadian factors become an integral part of translational research.

In mammals, non-visual responses to light involve intrinsically photosensitive melanopsin-expressing retinal ganglion cells (ipRGCs) that receive synaptic inputs from rod and cone photoreceptors. Several studies have shown that cones also play a role in light entrainment, photic responses of the suprachiasmatic nucleus (SCN), pupil constriction, and sleep induction. These studies suggest that cones are mainly involved in the initial response to light, whereas melanopsin provides a sustained input for nonvisual responses during continued light exposure. Based on this idea, we explored the effects of the absence of middle-wavelength (MW)-cones on the temporal responses of circadian behavior and clock gene expression in light. In mice lacking MW-cones, our results show a reduction in behavioral phase shifts in response to light stimulations of short duration at 480 and 530 nm, but no alteration for short-wavelength (360-nm) light exposures. Similarly, induction of the period gene mPer1 and mPer2 mRNAs in the SCN are attenuated in response to light exposures of mid to long wavelengths. Modeling of the photoresponses shows that mice lacking MW-cones have an overall reduction in sensitivity that increases with longer wavelengths. The differences in photic responsiveness are consistent with the idea that cones provide a strong initial phasic input to the circadian system at light-onset and may confer a priming effect on ipRGC responses to sub-threshold light exposures. In summary, the contribution of MW-cones is essential for the normal expression of phase shifts and clock gene induction by light in mammals.

Melatonin, the main hormone produced by the pineal gland, is secreted in a circadian manner (24‐hr period), and its oscillation influences several circadian biological rhythms, such as the regulation of clock genes expression (chronobiotic effect) and the modulation of several endocrine functions in peripheral tissues. Assuming that the circadian synchronization of clock genes can play a role in the regulation of energy metabolism and it is influenced by melatonin, our study was designed to assess possible alterations as a consequence of melatonin absence on the circadian expression of clock genes in the epididymal adipose tissue of male Wistar rats and the possible metabolic repercussions to this tissue. Our data show that pinealectomy indeed has impacts on molecular events: it abolishes the daily pattern of the expression of Clock, Per2, and Cry1 clock genes and Pparγ expression, significantly increases the amplitude of daily expression of Rev‐erbα, and affects the pattern of and ...

Nursing in the rabbit is under circadian control, and pups have a daily anticipatory behavioral arousal synchronized to this unique event, but it is not known which signal is the main entraining cue. In the present study, we hypothesized that food is the main entraining signal. Using mother‐deprived pups, we tested the effects of artificial feeding on the synchronization of locomotor behavior, plasma glucose, corticosterone, c‐Fos (FOS) and PERIOD1 (PER1) rhythms in suprachiasmatic, supraoptic, paraventricular and tuberomammillary nuclei. At postnatal day 1, an intragastric tube was placed by gastrostomy. The next day and for the rest of the experiment, pups were fed with a milk formula through the cannula at either 02:00 h or 10:00 h [feeding time = zeitgeber time (ZT)0]. At postnatal days 5–7, pups exhibited behavioral arousal, with a significant increase in locomotor behavior 60 min before feeding. Glucose levels increased after feeding, peaking at ZT4–ZT12 and then declining. Co...

Components of circadian rhythm maintenance, or "clock genes," are endogenous entrainable oscillations of about 24 h that regulate biological processes and are found in the suprachaismatic nucleus (SCN) and many peripheral tissues, including the heart. They are influenced by external cues, or Zeitgebers, such as light and heat, and can influence such diverse phenomena as cytokine expression immune cells, metabolic activity of cardiac myocytes, and vasodilator regulation by vascular endothelial cells. While it is known that the central master clock in the SCN synchronizes peripheral physiologic rhythms, the mechanisms by which the information is transmitted are complex and may include hormonal, metabolic, and neuronal inputs. Whether circadian patterns are causally related to the observed periodicity of events, or whether they are simply epi-phenomena is not well established, but a few studies suggest that the circadian effects likely are real in their impact on myocardial infarct incidence. Cycle disturbances may be harbingers of predisposition and subsequent response to acute and chronic cardiac injury, and identifying the complex interactions of circadian rhythms and myocardial infarction may provide insights into possible preventative and therapeutic strategies for susceptible populations.