Circadian rhythms modulate growth and development in all organisms through interlocking transcriptional-translational feedback loops. The transcriptional loop involves chromatin modifications of central circadian oscillators in mammals and plants. However, the molecular basis for rhythmic epigenetic modifications and circadian regulation is poorly understood. Here we report a feedback relationship between diurnal regulation of circadian clock genes and histone modifications in Arabidopsis. On one hand, the circadian oscillators CCA1 and LHY regulate diurnal expression of genes coding for the eraser (JMJ14) directly and writer (SDG2) indirectly for H3K4me3 modification, leading to rhythmic H3K4me3 changes in target genes. On the other hand, expression of circadian oscillator genes including CCA1 and LHY is associated with H3K4me3 levels and decreased in the sdg2 mutant but increased in the jmj14 mutant. At the genome-wide level, diurnal rhythms of H3K4me3 and another histone mark H3K9ac are associated

To screen for output signals that may distinguish the pacemaker in the mammalian suprachiasmatic nucleus (SCN) from peripheral-type oscillators in which the canonical clockworks are similarly regulated in a circadian manner, the rhythmic behavior of the transcriptome in forskolin-stimulated NIH/3T3 fibroblasts was analyzed and compared relative to SCN2.2 cells in vitro and the rat SCN. Similar to the circadian profiling of the SCN2.2 and rat SCN transcriptomes, NIH/3T3 fibroblasts exhibited circadian fluctuations in the expression of the core clock genes, Per2, Cry1, and Bmal1, and 323 functionally diverse transcripts, many of which regulate cellular communication. Overlap in rhythmic transcripts among NIH/3T3 fibroblasts, SCN2.2 cells, and the rat SCN was limited to these clock genes and four other genes that mediate fatty acid and lipid metabolism or function as nuclear factors. Compared with NIH/3T3 cells, circadian gene expression in SCN oscillators was more prevalent among genes mediating ...

TY - JOUR. T1 - Inhibition of protein kinase A phase delays the mammalian circadian clock. AU - Lee, Jennifer M.. AU - Schak, Kathryn M.. AU - Harrington, Mary E.. PY - 1999/7/24. Y1 - 1999/7/24. N2 - The suprachiasmatic nuclei (SCN) contain the mammalian circadian clock whose rhythm of firing rate can be recorded in vitro for several days. Application of a protein kinase A (PKA) inhibitor onto the SCN at Zeitgeber time (ZT) 10 on the first day in vitro phase delayed the rhythm of firing rate expressed by SCN neurons on the subsequent day in vitro. Application of the inhibitor (Rp-cAMPS) at other circadian phases did not phase shift the rhythm. These results suggest that during approximately 1 h in the late subjective day the presence and activity of PKA plays a role in setting the phase of the mammalian circadian clock.. AB - The suprachiasmatic nuclei (SCN) contain the mammalian circadian clock whose rhythm of firing rate can be recorded in vitro for several days. Application of a protein ...

Circadian systems represent an endogenous mechanism adapted to cycling environmental conditions. In mammals, the central circadian clock is located in the suprachiasmatic nuclei (SCN), guiding circadian-regulated biological variables such as the sleep-wake cycle, hormonal secretions and locomotor activity [1]. Another physiological process that exhibits circadian fluctuations, with obvious implications in disease progression and outcome, is the regulation of immune function.. The link between the circadian and the immune systems has been extensively investigated [2-4]. Circadian rhythms within the immune system were described in several tissues and cellular populations [5]. In humans, the number of lymphocytes and granulocytes peaks during the night, whereas monocytes and neutrophil levels fall during the day [6]. Major humoral immune responses undergo circadian changes, and rhythms in plasmatic levels of pro-inflammatory cytokines, as well as peptide hormones produced and secreted by immune ...

Circadian phase resetting in older people by ocular bright light exposure.. Aging is associated with frequent complaints about earlier bedtimes and waketimes. These changes in sleep timing are associated with an earlier timing of multiple endogenous rhythms, including core body temperature (CBT) and plasma melatonin, driven by the circadian pacemaker. One possible cause of the age-related shift of endogenous circadian rhythms and the timing of sleep relative to clock time is a change in the phase-shifting capacity of the circadian pacemaker in response to the environmental light-dark cycle, the principal synchronizer of the human circadian system. METHODS: We studied the response of the circadian system of 24 older men and women and 23 young men to scheduled exposure to ocular bright light stimuli. Light stimuli were 5 hours in duration, administered for 3 consecutive days at an illuminance of approximately 10,000 lux. Light stimuli were scheduled 1.5 or 3.5 hours after the CBT nadir to induce ...

In the context of bacterial circadian rhythms, specifically in cyanobacteria, circadian advantage refers to the improved survival of strains of cyanobacteria that resonate with the environmental circadian rhythm. [6] For example, consider a strain with a free-running period (FRP) of 24 hours is co-cultured with a strain that has a free-running period (FRP) of 30 hours in a light-dark cycle of 12 hours light and 12 hours dark (LD 12:12). The strain that has a 24 hour FRP will out-compete the 30 hour strain over time. An instance where bacterial circadian rhythms are theorized to provide an advantage is in the microbiome. It is possible that circadian clocks play a role in the gut microbiota behavior. These microorganisms experience daily changes associated with daily LD and temperature cycles through an alteration of their environment. This occurs through behaviors such as eating rhythms on a daily routine (consumption in the day for diurnal animals and in the night for nocturnal). The presence ...

Sleep and circadian rhythm disruption (SCRD) and schizophrenia are often co-morbid. Here, we propose that the co-morbidity of these disorders stems from the involvement of common brain mechanisms. We summarise recent clinical evidence that supports this hypothesis, including the observation that the treatment of SCRD leads to improvements in both the sleep quality and psychiatric symptoms of schizophrenia patients. Moreover, many SCRD-associated pathologies, such as impaired cognitive performance, are routinely observed in schizophrenia. We suggest that these associations can be explored at a mechanistic level by using animal models. Specifically, we predict that SCRD should be observed in schizophrenia-relevant mouse models. There is a rapidly accumulating body of evidence which supports this prediction, as summarised in this review. In light of these emerging data, we highlight other models which warrant investigation, and address the potential challenges associated with modelling schizophrenia and

All domains of life feature diverse molecular clock machineries that synchronize physiological processes to diurnal environmental fluctuations. However, no mechanisms are known to cross-regulate prokaryotic and eukaryotic circadian rhythms in multikingdom ecosystems. Here, we show that the intestinal microbiota, in both mice and humans, exhibits diurnal oscillations that are influenced by feeding rhythms, leading to time-specific compositional and functional profiles over the course of a day. Ablation of host molecular clock components or induction of jet lag leads to aberrant microbiota diurnal fluctuations and dysbiosis, driven by impaired feeding rhythmicity. Consequently, jet-lag-induced dysbiosis in both mice and humans promotes glucose intolerance and obesity that are transferrable to germ-free mice upon fecal transplantation. Together, these findings provide evidence of coordinated metaorganism diurnal rhythmicity and offer a microbiome-dependent mechanism for common metabolic ...

Background AMP protein kinase (AMPK) plays an important role in food intake and energy metabolism, which are synchronized to the light-dark cycle. In vitro, AMPK affects the circadian rhythm by regulating at least two clock components, CKIα and CRY1, via direct phosphorylation. However, it is not known whether the catalytic activity of AMPK actually regulates circadian rhythm in vivo. Methodology/Principal Finding The catalytic subunit of AMPK has two isoforms: α1 and α2. We investigate the circadian rhythm of behavior, physiology and gene expression in AMPKα1−/− and AMPKα2−/− mice. We found that both α1−/− and α2−/− mice are able to maintain a circadian rhythm of activity in dark-dark (DD) cycle, but α1−/− mice have a shorter circadian period whereas α2−/− mice showed a tendency toward a slightly longer circadian period. Furthermore, the circadian rhythm of body temperature was dampened in α1−/− mice, but not in α2−/− mice. The circadian pattern of core

Epicardial fat tissue is known to have an unique endocrine function which affect the cardiac autonomic system. Heart rate recovery (HRR) is a simple non-invasive measurement that assesses autonomic nervous system dysfunction. We aimed to investigate the association among epicardial fat thickness (EFT), HRR and circadian blood pressure (BP) variation in patients with hypertension. A total of 358 consecutive patients who underwent both 24-hour ambulatory BP monitoring (ABPM) and a treadmill test were enrolled. Echocardiographic EFT and HRR, defined as peak heart rate minus heart rate after a 1-min recovery time, were measured. Patients were classified according to the ABPM; 147 patients with hypertension with a dipping pattern at night (dippers), 140 patients with hypertension with a non-dipping pattern at night (non-dippers) and 71 normotensive controls. EFT was significantly higher in hypertensive patients, especially in the non-dipper group, compared to the controls (non-dippers, 7.5 ± 2.9 mm; dippers

The role of DOMINO in regulation of circadian rhythms in Drosophila. Most organisms on earth use circadian clocks to modulate their bodily functions, thus adapting their metabolism, physiology and behavior to these daily environmental cycles. Malfunctions of circadian clocks are correlated with many human diseases. For example, disrupted circadian rhythms in shift workers are thought to increase the prevalence of cancers, cardiovascular diseases, diabetes and other metabolic diseases. Circadian clocks control rhythmic expression of around 10-15% of mammalian transcripts. The fruit fly Drosophila melanogaster is an excellent model to study circadian clock because of its well-characterized genome, powerful genetics tools, and high throughput automated behavioral assays. In addition, the core of the circadian pacemaker is highly conserved among species, and the molecular mechanisms of circadian clocks were, in great part, discovered in Drosophila. Studying circadian rhythms in Drosophila has ...

The adrenal cortex has a molecular clock that generates circadian rhythms in glucocorticoid production, yet it is unclear how the clock responds to acute stress. We hypothesized that stress-induced ACTH provides a signal that phase shifts the adrenal clock. To assess whether acute stress phase shifts the adrenal clock in vivo in a phase-dependent manner, mPER2::LUC mice on a 12:12h light:dark cycle underwent restraint stress for 15 min or no stress at zeitgeber time (ZT) 2 (early subjective day) or at ZT16 (early subjective night). Adrenal explants from mice stressed at ZT2 showed mPER2::LUC rhythms that were phase-advanced by ~2h, whereas adrenals from mice stressed at ZT16 showed rhythms that were phase-delayed by ~2h. The biphasic response also was observed in mice injected subcutaneously either with saline or with ACTH at ZT2 or ZT16. Blockade of the ACTH response with the glucocorticoid, dexamethasone, prevented restraint stress-induced phase shifts in the mPER2::LUC rhythm both at ZT2 and at ZT16.

Circadian rhythms in physiology and behavior are observed in almost all phyla. Genetically encoded internal clocks generate such rhythms. Identification of gene products required for the generation and maintenance of endogenous circadian near 24-hr rhythms has led to a paradigm of multiple interlocked transcriptional/translational feedback loops as the basis for molecular circadian oscillators in all studied model systems. Protein phosphorylation plays an essential role, regulating the stability, activity and subcellular localization of proteins that constitute the biological clock. This study investigates the role of the protein kinase Doubletime, a Drosophila ortholog of casein kinase Is, in the fruit fly circadian clock. For the first time enzymatically active Doubletime protein is produced and direct phosphorylation of clock protein Period is demonstrated. Phosphorylation sites are identified and their functional significance is tested in a cell culture system. An in vivo analysis of a Period mutant

Circadian rhythm is an internal biological clock, which enables to sustain an approximately 24-hour rhythm in the absence of environmental cues. In mammals, the circadian clock mechanism consists of cell-autonomous transcription-translation feedback loops that drive rhythmic, 24-hour expression patterns of core clock components. The first negative feedback loop is a rhythmic transcription of period genes (PER1, PER2, and PER3) and chryptochrome genes (CRY1 and CRY2). PER and CRY proteins form a heterodimer, which acts on the CLOCK/BMAL1 heterodimer to repress its own transcription. PER and CRY proteins are phosphorylated by casein kinase epsilon (CKIepsilon), which leads to degradation and restarting of the cycle. The second loop is a positive feedback loop driven by the CLOCK/BMAL1 heterodimer, which initiates transcription of target genes containing E-box cis-regulatory enhancer sequences ...

Circadian clocks are endogenous timekeeping systems that adapt in an anticipatory fashion the physiology and behavior of most living organisms. In mammals, the master pacemaker resides in the suprachiasmatic nucleus and entrains peripheral clocks using a wide range of signals that differentially schedule physiology and gene expression in a tissue-specific manner. The peripheral clocks, such as those found in the liver, are particularly sensitive to rhythmic external cues like feeding behavior, which modulate the phase and amplitude of rhythmic gene expression. Consequently, the liver clock temporally tunes the expression of many genes involved in metabolism and physiology. However, the circadian modulation of cellular functions also relies on multiple layers of posttranscriptional and posttranslational regulation. Strikingly, these additional regulatory events may happen independently of any transcriptional oscillations, showing that complex regulatory networks ultimately drive circadian output

The effects of aging on thyroxine and cortisol responses to low ambient temperatures and on circadian rhythm of cortisol in the ...

Circadian clocks allow organisms to organize behavior and physiology to an approximately 24-hour rhythm, facilitating adaptation to the environmental cycle of day and night. Although circadian rhythms in mammals are most evident at an organismal level, circadian timekeeping occurs cell-autonomously (1). The clock in every cell and tissue is synchronized in vivo by systemic cues such as body temperature and glucocorticoid signaling, which are themselves coordinated by a master clock in the hypothalamic suprachiasmatic nuclei (2). There is mounting evidence that circadian disruption, associated with modern lifestyles and aging, contributes to morbidities as diverse as cancer, cardiovascular disease, and diabetes (3, 4). A major knowledge gap exists, however, between the well-characterized circadian gene expression rhythms that occur in healthy peripheral tissues in vivo and the way in which different cell types exploit their innate clockwork to achieve beneficial circadian regulation of cell ...

Circadian rhythms allow organisms to anticipate and prepare for precise and regular environmental changes. They thus enable organisms to better capitalize on environmental resources (e.g. light and food) compared to those that cannot predict such availability. It has therefore been suggested that circadian rhythms put organisms at a selective advantage in evolutionary terms. However, rhythmicity appears to be as important in regulating and coordinating internal metabolic processes, as in coordinating with the environment.[18] This is suggested by the maintenance (heritability) of circadian rhythms in fruit flies after several hundred generations in constant laboratory conditions,[19] as well as in creatures in constant darkness in the wild, and by the experimental elimination of behavioral, but not physiological, circadian rhythms in quail.[20][21]. What drove circadian rhythms to evolve has been an enigmatic question. Previous hypotheses emphasized that photosensitive proteins and circadian ...

Sleep and circadian rhythm disruption has been widely observed in neuropsychiatric disorders including schizophrenia [1] and often precedes related symptoms [2] . However, mechanistic basis for this association remains unknown. Therefore, we investigated the circadian phenotype of blind-drunk (Bdr), a mouse model of synaptosomal-associated protein (Snap)-25 exocytotic disruption that displays schizophrenic endophenotypes modulated by prenatal factors and reversible by antipsychotic treatment [3, 4]. Notably, SNAP-25 has been implicated in schizophrenia from genetic [5-8] , pathological [9-13], and functional studies [14-16] . We show here that the rest and activity rhythms of Bdr mice are phase advanced and fragmented under a light/dark cycle, reminiscent of the disturbed sleep patterns observed in schizophrenia. Retinal inputs appear normal in mutants, and clock gene rhythms within the suprachiasmatic nucleus (SCN) are normally phased both in vitro and in vivo. However, the 24 hr rhythms of arginine

Circadian rhythms, the biological oscillations based around our 24-hour clock, have a profound effect on human physiology and healthy cellular function. Circadian Rhythms: Health and Disease is a wide-ranging foundational text that provides students and researchers with valuable information on the molecular and genetic underpinnings of circadian rhythms and looks at the impacts of disruption in our biological clocks in health and disease.. Circadian Rhythms opens with chapters that lay the fundamental groundwork on circadian rhythm biology. Section II looks at the impact of circadian rhythms on major organ systems. Section III then turns its focus to the central nervous system. The book then closes with a look at the role of biological rhythms in aging and neurodegeneration.. Written in an accessible and informative style, Circadian Rhythms: Health and Disease,will be an invaluable resource and entry point into this fascinating interdisciplinary field that brings together aspects of ...

Nearly all organisms living near the surface of the Earth contain circadian (circa - about; diem- day) clocks functioning as an endogenous timekeeping mechanism by which the organism can coordinate biological processes with 24h cycles in the external environment (such as the daily light:dark cycle). In nature, the ~24h free-running oscillation of circadian clocks is synchronized or entrained with the precisely 24h solar day cycle. In mammals, the master circadian pacemaker is located in the hypothalamic suprachiasmatic nucleus (SCN) which regulates ~24h rhythms of biological activity. The master circadian pacemaker within the SCN modulates adrenal gland release of glucocorticoids (GCs). GCs are a class of steroids critical for the mobilization of energy throughout the organism. GCs are released from the adrenal cortex and exhibit a circadian oscillation anticipating the onset of locomotor activity. In addition to humoral input to the adrenal cortex via adrenocorticotropic hormone (ACTH), the ...

Circadian activity rhythms in hamsters are entrained to the daily light:dark cycle by photic information arriving from the retina to the suprachiasmatic nucleus, the site of the master circadian pacemaker in mammals. The effects of light on adjusting the timing of the circadian pacemaker is modified …

Circadian rhythms, the subset of endogenous rhythms with a period of approximately 24 h, are widely encountered in most organisms from cyanobacteria to humans. Although eukaryotes employ a common mechanistic logic of interlocked negative feedback loops to generate robust circadian oscillations, different components have been recruited to form the clock in different taxa (Bell-Pedersen et al., 2005; McClung, 2006; Wijnen and Young, 2006). Thus, fungal, animal, and plant clocks share a common architectural plan yet are composed of largely distinct components. This suggestion of polyphyletic origins of clocks implies strong selection for clock function. Indeed, in many organisms, including cyanobacteria, fruit fly, ground squirrel, and Arabidopsis (Arabidopsis thaliana), experimental evidence indicates that a robust circadian clock whose period resonates with the environmentally imposed diurnal cycle confers a fitness advantage (Yerushalmi and Green, 2009).. Among plants, most that is known about ...

Circadian rhythms, the subset of endogenous rhythms with a period of approximately 24 h, are widely encountered in most organisms from cyanobacteria to humans. Although eukaryotes employ a common mechanistic logic of interlocked negative feedback loops to generate robust circadian oscillations, different components have been recruited to form the clock in different taxa (Bell-Pedersen et al., 2005; McClung, 2006; Wijnen and Young, 2006). Thus, fungal, animal, and plant clocks share a common architectural plan yet are composed of largely distinct components. This suggestion of polyphyletic origins of clocks implies strong selection for clock function. Indeed, in many organisms, including cyanobacteria, fruit fly, ground squirrel, and Arabidopsis (Arabidopsis thaliana), experimental evidence indicates that a robust circadian clock whose period resonates with the environmentally imposed diurnal cycle confers a fitness advantage (Yerushalmi and Green, 2009).. Among plants, most that is known about ...

TY - JOUR. T1 - Investigating the relationships between hypothalamic volume and measures of circadian rhythm and habitual sleep in premanifest Huntingtons disease. AU - Bartlett, Danielle M.. AU - Domínguez D, Juan F.. AU - Reyes, Alvaro. AU - Zaenker, Pauline. AU - Feindel, Kirk W.. AU - Newton, Robert U.. AU - Hannan, Anthony J.. AU - Slater, James A.. AU - Eastwood, Peter R.. AU - Lazar, Alpar S.. AU - Ziman, Mel. AU - Cruickshank, Travis. PY - 2019/1. Y1 - 2019/1. N2 - Objective: Pathological changes within the hypothalamus have been proposed to mediate circadian rhythm and habitual sleep disturbances in individuals with Huntingtons disease (HD). However, investigations examining the relationships between hypothalamic volume and circadian rhythm and habitual sleep in individuals with HD are sparse. This study aimed to comprehensively evaluate the relationships between hypothalamic pathology and circadian rhythm and habitual sleep disturbances in individuals with premanifest HD. Methods: ...

OBJECTIVE: Physical activity and circadian rhythms are well-established determinants of human health and disease, but the relationship between muscle activity and the circadian regulation of muscle genes is a relatively new area of research. It is unknown whether muscle activity and muscle clock rhythms are coupled together, nor whether activity rhythms can drive circadian gene expression in skeletal muscle. METHODS: We compared the circadian transcriptomes of two mouse hindlimb muscles with vastly different circadian activity patterns, the continuously active slow soleus and the sporadically active fast tibialis anterior, in the presence or absence of a functional skeletal muscle clock (skeletal muscle-specific Bmal1 KO). In addition, we compared the effect of denervation on muscle circadian gene expression. RESULTS:We found that different skeletal muscles exhibit major differences in their circadian transcriptomes, yet core clock gene oscillations were essentially identical in fast and slow ...

Hazlerigg, DG, Ebling, FJP and Johnston, JD (2005) Photoperiod differentially regulates gene expression rhythms in the rostral and caudal SCN ...

Purpose : Changes in eye growth that lead to myopia or hyperopia are associated with alterations in the circadian rhythms in eye length and choroidal thickness in animal models. Recent studies have shown that light at night has deleterious effects on human health via circadian disruptions in various physiological rhythms. The purpose of this study was to determine the effects of 2-hour episodes of light at night on the rhythms in axial length and choroidal thickness, and on growth rate and refraction in the chick model. Methods : At 2 weeks of age, birds received light (700 lux) between 12:00 am and 2:00 am for 7 days (n=18; total light=14 hr). Age-matched controls had a continuous dark night (n=22; 14L/10D). Ocular dimensions were measured using high-frequency A-scan ultrasonography on the first day, and again on day 7 at 6-hr intervals for 24 hr, starting at noon. Measurements during the night used a photographic safe-light. These data were used to determine rhythm parameters of phase and ...

Synchrony of the mammalian circadian clock is achieved by complex transcriptional and translational feedback loops centered on the BMAL1:CLOCK heterodimer. Modulation of circadian feedback loops is essential for maintaining rhythmicity, yet the role of transcriptional coactivators in driving BMAL1:CLOCK transcriptional networks is largely unexplored. Here, we show diurnal hepatic steroid receptor coactivator 2 (SRC-2) recruitment to the genome that extensively overlaps with the BMAL1 cistrome during the light phase, targeting genes that enrich for circadian and metabolic processes. Notably, SRC-2 ablation impairs wheel-running behavior, alters circadian gene expression in several peripheral tissues, alters the rhythmicity of the hepatic metabolome, and deregulates the synchronization of cell-autonomous metabolites. We identify SRC-2 as a potent coregulator of BMAL1:CLOCK and find that SRC-2 targets itself with BMAL1:CLOCK in a feedforward loop. Collectively, our data suggest that SRC-2 is a ...

Circadian rhythms are essential for healthful cardiovascular physiology and so are regulated on the molecular level with a circadian clock mechanism. and BMAL1 targeted Bardoxolone genes using the CircaDB JTK_Cycle and internet site. Furthermore 22 were expressed in the center as dependant on the BioGPS internet site highly. Furthermore 5 Bardoxolone heart-enriched genes acquired individual/mouse conserved CLOCK:BMAL1 promoter binding sites (E-boxes) as dependant on UCSC table web browser circadian mammalian promoter/enhancer data source PEDB as well Bardoxolone as the Western european Bioinformatics Institute position tool (EMBOSS). Finally we validated results by demonstrating that (mRNA and TCAP protein experienced a diurnal rhythm in murine heart; 2) cardiac mRNA was rhythmic in animals kept in constant darkness; 3) and control mRNA manifestation and cyclic amplitude were blunted in ClockΔ19/Δ19 hearts; 4) BMAL1 certain to the promoter by ChIP assay; 5) BMAL1 certain to promoter E-boxes by ...

The rotation of the earth around its axis and the sun generates rhythmic daily and seasonal cycles in our world. Organisms have evolved a biological clock to be able to predict and follow environmental cyclic rhythms to control their physiology and behavior for survival. In mammals the master clock is located in the suprachiasmatic nucleus (SCN) of the hypothalamus which receives light inputs via retinohypothalamic tract directly from the retina to be entrained to external cycles. Circadian rhythms are maintained by two negative feedback loops involving several clock genes such as Clock, Bmal1, Period, Cryptochrome and Rev-erbα. Apart from the central master clock, there are several peripheral clocks controlling local feature of organs in synchrony with the SCN. One of these peripheral circadian oscillators is the retina which is the one that processes the light cues and may influence the circadian rhythms generated by the SCN.. We are interested how the visual system adjust itselves to the ...

The rhythmic genes we have identified under LD and DD conditions display bone fide rhythmic expression. The inclusion of seven known rhythmic genes (per, tim, vri, Clk, Dreg-2, cry, and takeout) in the set of 72 diurnally oscillating genes and four (per, tim, vri, and Clk) in the set of 22 circadianly oscillating genes provides confidence that the autocorrelation method we applied identifies rhythmic gene expression with fidelity.. The true number of circadianly regulated genes in Drosophila can only be estimated; the accuracy of any estimate depends on both methodological constraints and assumptions used in the data analysis. Our estimates of 72-200 robustly oscillating genes in LD 12:12 and a minimum of 22 genes in DD likely underestimate the true number of oscillating genes in the fly head. First, by necessity the choices of A0 minima were determined empirically. In the absence of true positive controls (i.e., rhythmically spiked foreign, polyadenylated message), we relied on the reproducible ...

In Arabidopsis thaliana, a number of circadian-associated factors have been identified, including TOC1 (TIMING OF CAB EXPRESSION 1) that is believed to be a component of the central oscillator. TOC1 is a member of a small family of proteins, designated as ARABIDOPSIS PSEUDO-RESPONSE REGULATORS (APRR1/TOC1, APRR3, APRR5, APRR7, and APRR9). As demonstrated previously, these APRR1/TOC1 quintet members are crucial for a better understanding of the molecular links between circadian rhythms, control of flowering time through photoperiodic pathways, and also photosensory signal transduction in this dicotyledonous plant. In this respect, both the dicotyledonous (e.g. A. thaliana) and monocotyledonous (e.g. Oryza sativa) plants might share the evolutionarily conserved molecular mechanism underlying the circadian rhythm. Based on such an assumption, and as the main objective of this study, we asked the question of whether rice also has a set of pseudo-response regulators, and if so, whether or not they ...

In the last 50 years, research on circadian rhythms has grown from understanding the basics to being able to map out intricate orchestrations for various systems. An article entitled Perfect timing: circadian rhythms, sleep, and immunity - an NIH workshop summary and other recent articles helps shed light on the circadian rhythms and immune health. This timely article from January 2020 gives us insight into current immune-challenging concerns. It tells us that disruption of day-night routines and circadian rhythms profoundly impacts essential immune functions and weakens health. Restoration of healthy day-night, wake-sleep routines supports your circadian rhythm and body clocks which helps immune system function and vitality ...

TY - JOUR. T1 - The relationships between clinical characteristics, alcohol and psychotropic exposure, and circadian gene expression in human postmortem samples of affective disorder and control subjects. AU - Gonzalez, Robert. AU - Bernardo, Carmina. AU - Cruz, Dianne. AU - Walss-Bass, Consuelo. AU - Thompson, Peter M.. PY - 2014/8/30. Y1 - 2014/8/30. N2 - Circadian abnormalities may be related to mood disorders. Circadian gene expression was measured in postmortem brain tissue from individuals with affective disorders and controls. Relationships between circadian gene expression, clinical characteristics, and alcohol and psychotropic medication use were noted. Further study is warranted to characterize these relationships.. AB - Circadian abnormalities may be related to mood disorders. Circadian gene expression was measured in postmortem brain tissue from individuals with affective disorders and controls. Relationships between circadian gene expression, clinical characteristics, and alcohol ...

new volumes of Methods in Enzymology proceed the legacy of this foremost serial with caliber chapters authored by means of leaders within the box. Circadian Rhythms and organic Clocks half A and half B is an outstanding source for anyone drawn to the overall region of circadian rhythms. As key parts of timekeeping are conserved in organisms around the phylogenetic tree, and our realizing of circadian biology has benefited significantly from paintings performed in lots of species, the amount offers a variety of assays for various organic systems. Protocols are supplied to evaluate clock functionality, entrainment of the clock to stimuli corresponding to mild and foodstuff, and output rhythms of habit and physiology. This quantity additionally delves into the impression of circadian disruption on human health. Contributions are from leaders within the box whove made significant discoveries utilizing the equipment awarded here.. ...

Epigenetic Modulation of Circadian Rhythms: Bmal1 Gene Regulation. By Tatsunosuke Tomita and Yoshiaki Onishi. Circadian rhythms that function in behaviour and physiology have adaptive significance for living organisms from bacteria to humans and reflect the presence of a biological clock. The engine of circadian rhythms is a transcription-translation feedback loop that is fine-tuned by epigenetic regulation in higher eukaryotes. We elucidated the chromatin structure of the Bmal1 gene, a critical component of the mammalian clock system, and have continued to investigate transcriptional regulation including DNA methylation. Various ailments including metabolic diseases can disrupt circadian rhythms, and many human diseases are associated with altered DNA methylation. Therefore, regulated circadian rhythms are important for human health. Here, we summarise the importance of epigenetic clock gene regulation, including DNA methylation of the Bmal1 gene, from the viewpoint of relationships to ...

This is the first study to show that RICTOR/mTORC2 acts as a regulator for coordinated diurnal expression of clock genes in PVAT, but not in the SCN. At the whole body level, RICTOR/mTORC2 in adipose and brain tissue contributes to the diurnal regulation of blood pressure and locomotor activity. The presented data demonstrate the importance of the mTORC2 signaling pathway in the brain to adipocyte axis for daily fluctuations of physiological processes.. We and others have recently shown that mTORC2 activity controls inflammatory molecule expression using tissue-specific Rictor knockout mouse models.7,20 We showed that vascular contractility in RictoraP2KO mice is increased because of enhanced secretion of proinflammatory cytokines in PVAT.7 Ablation of Rictor strongly reduced AKTSer473 phosphorylation, resulting in impaired mTORC2 signaling.5-7 Consequently, we assign the observed changes in RictoraP2KO mice to the impaired mTORC2 downstream signaling.. In this study, we explored these findings ...

The human sleep-wake cycle is generated by a circadian process, originating from the suprachiasmatic nuclei, in interaction with a separate oscillatory process: the sleep homeostat. The sleep-wake cycle is normally timed to occur at a specific phase relative to the external cycle of light-dark exposure. It is also timed at a specific phase relative to internal circadian rhythms, such as the pineal melatonin rhythm, the circadian sleep-wake propensity rhythm, and the rhythm of responsiveness of the circadian pacemaker to light. Variations in these internal and external phase relationships, such as those that occur in blindness, aging, morning and evening, and advanced and delayed sleep-phase syndrome, lead to sleep disruptions and complaints. Changes in ocular circadian photoreception, interindividual variation in the near-24-h intrinsic period of the circadian pacemaker, and sleep homeostasis can contribute to variations in external and internal phase. Recent findings on the physiological and molecular

Circadian entrainment is a fundamental property by which the period of the internal biological clock is entrained by recurring exogenous signals, such that the organisms endocrine and behavioral rhythms are synchronized to environmental cues. In mammals, a master clock is located in the suprachiasmatic nuclei (SCN) of the hypothalamus and may synchronize circadian oscillators in peripheral tissues. Light signal is the dominant synchronizer for master SCN clock. Downstream from the retina, glutamate and PACAP are released and trigger the activation of signal transduction cascades, including CamKII and nNOS activity, cAMP- and cGMP-dependent protein kinases, and mitogen-activated protein kinase (MAPK). Of non-photic entrainment, important phase shifting capabilities have been found for melatonin, which inhibits light-induced phase shifts through inhibition of adenylate cyclase (AC). Multiple entrainment pathways converge into CREB regulation. In turn, phosphorylated CREB activates clock gene ...

In mammals, the suprachiasmatic nucleus (SCN) of the hypothalamus constitutes the central circadian pacemaker. The SCN receives light signals from the retina and controls peripheral circadian clocks (located in the cortex, the pineal gland, the liver, the kidney, the heart, etc.). This hierarchical organization of the circadian system ensures the proper timing of physiological processes. In each SCN neuron, interconnected transcriptional and translational feedback loops enable the circadian expression of the clock genes. Although all the neurons have the same genotype, the oscillations of individual cells are highly heterogeneous in dispersed cell culture: many cells present damped oscillations and the period of the oscillations varies from cell to cell. In addition, the neurotransmitters that ensure the intercellular coupling, and thereby the synchronization of the cellular rhythms, differ between the two main regions of the SCN. In this work, a mathematical model that accounts for this heterogeneous

Disruption of two genes that control circadian rhythms can lead to diabetes, a researcher at UT Southwestern Medical Center has found in an animal study.. Mice with defective copies of the genes, called CLOCK and BMAL1, develop abnormalities in pancreatic cells that eventually render the cells unable to release sufficient amounts of insulin.. These results indicate that disruption of the daily clock may contribute to diabetes by impairing the pancreas ability to deliver insulin, said Dr. Joseph Takahashi, an investigator with the Howard Hughes Medical Institute at UT Southwestern and co-senior author of the study, which appeared in the journal Nature. Dr. Takahashi, who recently joined UT Southwestern as chairman of neuroscience, performed the research with colleagues when he was at Northwestern University.. Circadian rhythms are cyclical patterns in biological activities, such as sleeping, eating, body temperature and hormone production.. The mammalian CLOCK gene, which Dr. Takahashi ...

Introduction. World Literature Essay II: C Candidate Number: 000 119 023 Word Count:1071 Total Number of Pages: 4 The Individual vs. The Party in Darkness at Noon by Arthur Koestler Purpose Statement: The fundamental believes of the Party explained by Arthur Koestler were oppressive to the ideological believes of the individual. In return the revolution failed to reach a utopian society due to the oppression of the individual. The party describe in Darkness at Noon by Arthur Koestler represents the governmental and economic system of communism in the Soviet Union during the 1930s and 40s with the main intend of reaching a utopia in the real world. The sacrifice of the individual was necessary to carry out the will of history in the eyes of the party. The ideology of the party creates a conflict in Darkness at Noon where the ideologies of the party undermined the ideas of the grammatical fiction with a result of a failed revolution. An individual perception is needed to help the rest of ...

Organisms possess endogenous clocks that enable them to synchronize to diurnal environmental cycles and anticipate time of day. In several model systems, it is known that the circadian molecular clock consists of transcriptional/translational autoregulatory feedback loops in which clock proteins translocate to the nucleus and regulate clock gene transcription (Reppert and Weaver, 2002; Dunlap and Loros, 2005; Hardin, 2005). In Drosophila, the molecular oscillator is composed of three feedback loops which are interlocked by virtue of the CLK control of per and tim gene transcription. The first loop results in rhythmic PERIOD (PER) and TIMELESS (TIM) clock protein production, the second generates rhythms in the CLOCK (CLK) transcription factor and the third (Clockwork Orange) modulates the expression of several clock genes known to be regulated by the CLK transcription factor by binding to the E-box regulatory element (Glossop et al., 1999; Cyran et al., 2003; Glossop et al., 2003; Yu et al., ...

The present study demonstrated that under strictly controlled dietary conditions plasma levels of Hcy shows significant daily rhythmicity, which is independent of the 24-h cycle of sleep and wake, with a peak at around 2200 to 2400. Previously, similar rhythmicity in Hcy with an evening peak was reported in obese diabetic patients by Bremner et al [12] and with nocturnal peak in rats by Baydas et al [13]. We further extended these findings by demonstrating that daily rhythms exist also in normal young adults. In contrast to Hcy, there was no daily rhythmicity in methionine, leucine, isoleucine and tyrosine, in which the 24-h pattern followed both the timing of sleep and the feeding schedule.. Homocysteine is a non-protein sulfur containing amino acid, and an intermediate in the metabolism of the essential amino acid methionine. The metabolism of Hcy is accomplished by two major pathways, remethylation into methionine and transsulfuration to cystationine [14]. In remethylation, Hcy acquires a ...

This study provides critical evidence in support of the hypothesis that activation of NMDA receptors is a sufficient and necessary step in the transduction of photic information to the circadian clock located in the SCN. Previous research had demonstrated that microinjection of either NMDA antagonists or non-NMDA antagonists into the SCN region could block the phase-shifting effects of light (Colwell and Menaker, 1992) and that application of glutamate to the hypothalamic slice preparation could phase shift the SCN neuronal firing rhythm in a pattern similar to that produced by light pulses in vivo(Ding et al., 1994). Recently, we demonstrated that microinjection of NMDA into the SCN region was capable of producing both phase delays and phase advances of the circadian locomotor activity rhythm (Mintz and Albers, 1997). This paper extends that finding to demonstrate that direct application of NMDA to the SCN in vivo produces a light-like phase-response curve, that this effect is specific to NMDA ...

Diurnal Fluctuations of Symptoms Symptom Checker: Possible causes include 6-Pyruvoyl-Tetrahydropterin Synthase Deficiency. Check the full list of possible causes and conditions now! Talk to our Chatbot to narrow down your search.

Organisms face unforeseen short- and long-term changes in the environment (stressors). To defend against these changes, organisms have developed a stress system that includes the hypothalamic-pituitary-adrenal (HPA) axis, which employs glucocorticoids and the glucocorticoid receptor (GR) for signal transduction. In addition, organisms live under the strong influence of day-night cycles and, hence, have also developed a highly conserved circadian clock system for adjusting their activities to recurring environmental changes. This regulatory system creates and maintains internal circadian rhythmicity by employing a self-oscillating molecular pacemaker composed of the Clock-Bmal1 heterodimer and other transcription factors. The circadian clock consists of a central master clock in the suprachiasmatic nucleus of the brain hypothalamus and peripheral slave clocks in virtually all organs and tissues. The HPA axis and the circadian clock system communicate with each other at multiple levels. The ...

Proper timing of circadian rhythm requires stable oscillations in regulatory protein abundance and activity within a transcription-translation negative feedback loop that drives expression of circadian regulators and output genes. While their molecular functions are not fully understood, mPER1 and mPER2 have the highest amplitude oscillations of all the known core clock proteins, with almost complete degradation near the end of the subjective night in the suprachiasmatic nucleus (25). mPER2 also undergoes temporal changes in phosphorylation that reaches a zenith just prior to its destruction (25).. To study phosphorylation-mediated mPER2 degradation, a combination of cell-based assays were used. Calyculin A treatment of cultured cells resulted in the rapid phosphorylation and degradation of mPER2, suggesting that both a kinase and phosphatase regulate mPER2 net phosphorylation and stability. The present study further defines the role of CKIε in regulating mPER2 protein stability in mammals. ...

In mammals, molecular circadian rhythms are generated by autoregulatory transcriptional-translational feedback loops with PERIOD/CRYPTOCHROME containing complexes inhibiting the transcription of their own genes. Although the major circadian oscillator components seem to be identified, an increasing …