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 ...
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 ...
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 ...
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 ...
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 ...
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 ...
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 ...
Altered natural rhythms Although circadian rhythms are endogenous to every living organism on earth they are largely influenced by natural daylight. Thus in space, where the normal rhythm of daylight/night cycling no longer exists, these circadian rhythms are perturbed. This has an impa…
Video articles in JoVE about circadian rhythm include In Vitro Bioluminescence Assay to Characterize Circadian Rhythm in Mammary Epithelial Cells, Design and Analysis of Temperature Preference Behavior and its Circadian Rhythm in Drosophila, Parallel Measurement of Circadian Clock Gene Expression and Hormone Secretion in Human Primary Cell Cultures, Recording and Analysis of Circadian Rhythms in Running-wheel Activity in Rodents, Monitoring Cell-autonomous Circadian Clock Rhythms of Gene Expression Using Luciferase Bioluminescence Reporters, The FlyBar: Administering Alcohol to Flies, Blue-hazard-free Candlelight OLED, Assaying Locomotor Activity to Study Circadian Rhythms and Sleep Parameters in Drosophila, Slice Preparation, Organotypic Tissue Culturing and Luciferase Recording of Clock Gene Activity in the Suprachiasmatic Nucleus, Measuring Circadian and Acute Light Responses in Mice using Wheel Running Activity, Analysis of Circadian Photoresponses in Drosophila Using Locomotor
Study Design and Patient Selection. Our main hypothesis is that elevated circulating levels of tumor-associated cytokines could significantly alter the QOL of cancer patients through the production of circadian clock dysfunction.. A prospectively studied population of 200 consecutive metastatic colorectal cancer patients referred for systemic chronochemotherapy at Paul-Brousse Hospital, Villejuif, France served as the index population as previously reported (5). Before receiving chronochemotherapy, these patients had rest/activity monitoring with wrist actigraphy and serum cortisol rhythm assessment as part of their initial work up. The analysis of the rest/activity records allowed the ranking of the patients according to r24, a robust index of the circadian rhythmicity in activity (see below). From these 200 patients, 80 were selected based upon r24 ranking. Forty patients in the top quartile displayed near normal circadian rhythm (group I) and 40 other patients in the lowest quartile had ...
Sleep-wake patterns observed by a circadian rhythm disruption protocol. White bar: light cycle, Black bar: dark cycle, Gray bar: dark cycle during disruption ph
Biological rhythms are driven by circadian oscillators, which are ultimately controlled by the cyclic expression of clock genes. Cryptochromes (CRY), blue light photoreceptors, belong to the negative elements of the transcriptional feedback loop into the molecular clock. This paper describes the cloning and characterization of two cryptochromes (cry1 and 2) in European seabass, which is considered an interesting chronobiology model due to its dual (diurnal/nocturnal) behavior. The cloned cDNA fragments encoded for two proteins of 567 and 668 amino acids, which included the FAD-binding and the DNA-photolyase domains. Moreover, both proteins had a high homology with cryptochrome proteins (Cry) of other teleost fish. These cry1 and 2 genes were expressed in several tissues of seabass (brain, liver, heart, retina, muscle, spleen, gill and intestine). In addition, the daily expression of cry1 was rhythmic in brain, heart and liver with the acrophase around ZT 03:15 h (after the onset of lights). ...
Circadian rhythms in health and disease. We investigate cellular mechanisms underlying circadian rhythmicity and how these can be altered in diseases and conditions that are characterized by sleep and rhythm dysfunctions.. Human physiology and behavior undergo daily (circadian = 24 hr) rhythms that are generated by an internal "body clock", the hypothalamic suprachiasmatic nuclei (SCN). Rhythms may become disturbed by internal or external factors, for instance in "jet lag", which occurs after rapid traveling across time zones. Disturbed rhythms are also common in certain psychiatric disorders, neurodegenerative diseases and aging. Deciphering all components in the circadian machinery is a prerequisite for developing new therapeutic strategies to treat circadian rhythm disorders, and to bridge circadian research to the clinics.. Circa 24-h rhythmicity is generated by molecular feedback loops of rhythmically expressed genes and their protein products. Recent studies suggest that also neuronal ...
LA JOLLA, CA-Scientists have known for some time that throwing off the bodys circadian rhythm can negatively affect body chemistry. In fact, workers whose sleep-wake cycles are disrupted by night shifts are more susceptible to chronic inflammatory diseases such as diabetes, obesity and cancer.. Researchers at the Salk Institute for Biological Studies have now found a possible molecular link between circadian rhythm disturbances and an increased inflammatory response. In a study published July 9 in Proceedings of the National Academy of Sciences, the Salk team found that the absence of a key circadian clock component called cryptochrome (CRY) leads to the activation of a signaling system that elevates levels of inflammatory molecules in the body.. "There is compelling evidence that low-grade, constant inflammation could be the underlying cause of chronic diseases such as diabetes, obesity and cancer," says senior author Inder Verma, a professor in Salks Laboratory of Genetics and the Irwin and ...
All cells possess a molecular circadian ?clock? thought to coordinate various aspects of the physiology and behavior of an animal with the light/dark cycle of the external world. Light is the principle cue entraining molecular clocks via the suprachiasmatic nucleus of the brain. Recent evidence however, has also implicated food-borne signals as external stimuli capable of resetting clocks in the periphery. The aim of this study was to investigate the impact of aberrant feeding on circadian energy metabolism in the rat by feeding a high fat diet and restricting feeding to the daylight hours. Here we show that rats on the daylight feeding and high-fat feeding schedules displayed various differences in metabolism including hormone and metabolite levels and gene and protein expression. In the liver the circadian expression pattern of molecular clock genes was completely reversed in response to the new feeding schedule. In contrast, circadian gene expression in muscle remained similar to an animal feeding ad
In this reflection, perhaps we can consider but one line in the Gospel which both challenges our love, and is a sign of Gods humble and abiding love for us: For there was no room for them in the Inn.. I. The Cold - There is a knock at midnight. Joseph, speaking on behalf of both Mary and Jesus (who is in her womb still), seeks entrance to the homes and lodgings of those in Bethlehem. And even though the Jewish people placed a great deal of emphasis on the duty of hospitality to strangers, the answer repeatedly given is that there is "No room here." Marys obviously advanced pregnancy seems to make little difference.. This was indeed a cold night, not so much in terms of the air temperature, but in terms of the hearts of the people. Even at the local inn (and surely someone could make room for a pregnant woman!), there was "No room.". Yes, it was a cold night! The only warmth would be found among the animals of that town. An old Latin antiphon for Christmas says, O magnum mysterium et admirabile ...
... What Are Circadian Rhythms? Circadian rhythms influence our body temperature, sleep and wakefulness, and various hormonal changes.
Circadian clocks regulate daily patterns of behavior, metabolism, and immune system function. At the core of the clock are transcriptional and translational feedback loops that generate periodic, oscillating changes in the abundance of clock components. One of these loops involves the action of the transcription factors CLOCK and BMAL1, heterodimers of which stimulate the expression of genes encoding the transcription factors Period 1 and Period 2 (PER1 and PER2). PER1 and PER2 accumulate in the cytoplasm, translocate into the nucleus, and inhibit transcription of Clock and Bmal1. The timing of transcription and translation of clock components is important for determining the clocks periodicity, and Chen et al. report that microRNAs (miRNAs) play a key role in this timing mechanism. Because the circadian clock is essential for early development, the authors used mice harboring a conditional knockout of Dicer, which encodes a critical component of the miRNA processing machinery, to assess the ...
The human body functions according to a circadian rhythm thought to be controlled by a biological clock located in the part of the brain called the hypothalamus. There are several distinct disorders of our circadian rhythm and these are listed below: ...
In collaboration with Hajime Tei, Ph.D., who successfully cloned a mammalian homologue of the Drosophila period gene, we developed a rodent model for monitoring real-time circadian gene expression rhythm by bioluminescence.. Using this technique, we discovered circadian clocks in mammalian peripheral organs. As a result, we view the mammalian circadian system as a multi-oscillator system, rather than a system controlled by one pacemaker structure in the SCN.. The discovery also allows biochemical analysis to be performed in abundant tissues such as the liver, which accelerated understanding of the molecular mechanisms of timekeeping. We realized that out-of-sync relationships among clocks in peripheral organs contribute to many human diseases. Every tissues internal circadian rhythm delicately controls the local physiology of that tissue; even small changes in that timing can result in malaise, such as metabolic syndrome and obesity.. ...
A biological clock exists in many organisms and controls rhythmic behaviors such as the activity pattern of locomotion. At the cellular level, it has been shown that circadian rhythms in the morphology of neurons exist in the fruit fly Drosophila melanogaster. The studies presented in this thesis contribute to an increased understanding of this novel aspect of neuronal plasticity and its regulation.. We demonstrated the existence of a circadian rhythm in the morphology of neuromuscular terminals that innervate two identified flight muscles. Synaptic boutons are larger during the day than during the night under light:dark conditions (LD) as well as in constant darkness (DD). However, this rhythm is abolished in normal flies older than 30 days and in arrhythmic ones with null mutations in the clock genes period (per) or timeless (tim). Furthermore, these clock mutants show a completely different branching pattern indicating that the proteins PER and TIM not only function in well-described ...
To test the circadian rhythm of fruit flies, Sehgal and others exposed wild type (control) and mutant flies to several light and dark settings constant darkness, constant light, and equal periods of light and darkness (a light-dark cycle). During exposure to constant light for one week, the controls developed a disrupted sleep pattern after a few days, while the mutants maintained a regular circadian rhythm. The mutant and control flies displayed no behavioral differences during their exposure to constant darkness and the light-dark cycle. However, when the fruit flies were shifted from one light-dark cycle to another, the mutant flies took two days longer to adjust their sleep-wake cycle to the new light-dark schedule ...
To test the circadian rhythm of fruit flies, Sehgal and others exposed wild type (control) and mutant flies to several light and dark settings constant darkness, constant light, and equal periods of light and darkness (a light-dark cycle). During exposure to constant light for one week, the controls developed a disrupted sleep pattern after a few days, while the mutants maintained a regular circadian rhythm. The mutant and control flies displayed no behavioral differences during their exposure to constant darkness and the light-dark cycle. However, when the fruit flies were shifted from one light-dark cycle to another, the mutant flies took two days longer to adjust their sleep-wake cycle to the new light-dark schedule ...
Many organisms have ≈24-h rhythms in metabolism, physiology, and behavior that are driven by cell autonomous circadian pacemakers (1). These circadian rhythms allow organisms to coordinate a myriad of physiological processes with the changing environment. In mammals, the circadian pacemaker is composed of interlocked transcription-translation feedback loops: the primary loop is composed of the basic helix-loop-helix transcription factors CLOCK and BMAL1, which drive transcription of the Period (Per1, Per2) and Cryptochrome (Cry1, Cry2) genes (1, 2). PER and CRY proteins form the negative limb of the feedback loop by inhibiting their own CLOCK:BMAL1-induced transcription; turnover of PER and CRY allows the cycle to begin anew. The interlocked loop consists of REV-ERB-α and RORα, which repress and activate the Bmal1 gene, thereby modulating its function (3, 4). Mutation or deletion of Clock (5), Bmal1 (6), Per1/2 genes (7, 8), or Cry1/2 (9, 10) genes results in behavioral arrhythmicity and ...
Circadian rhythms are mechanisms that measure time on a scale of about 24 h and that adjusts our body to external environmental signals. Core circadian clock genes are defined as genes whose protein products are necessary components for the generation and regulation of circadian rhythms. Circadian proteins also regulate genes involved in either cell division or death; and a perturbation of the balance among these processes leads to cancer development and progression.. A key aspect of cancer research is identifying new regulatory pathways involved in proliferation and differentiation of cell. Disruption of circadian rhythm has recently emerged as a new potential risk factor in the development of cancer, pointing to the core gene period 2 (per2) as a tumor suppressor. However, it remains unclear how the circadian network regulates tumor suppression, nor which, if any, of its components is either the ultimate effector that influences the fate of the cell.. Initial experiments were devoted to ...
Pittsburgh-atonians, take note! Friday July 18th, at midnight (so, technically Saturday the 19th, but you know what I mean - wake up Friday, do your thing, then go see the movie at midnight), Saturday July 19th at midnight, and Sunday July 20th at 10PM, The Oaks Theater will be showing Ghostbusters as part of their 6th Annual Moonlight Matinees. Thanks to Eric for the tip. For more information on the showings, check here.. ...
Till Roenneberg, a chronobiologist in Munich, has mapped the circadian rhythms of more than 200,000 people.[2] Biological processes, including sleep-wake patterns, that display an oscillation of about 24 hours are called circadian rhythms. According to Roenneberg, the distribution of circadian rhythms spans from the very early to the very late chronotypes, similarly to how height varies from short to tall.[3] As circadian rhythm is independent of the number of hours of sleep a person needs, Roenneberg calculates the rhythm based on the midpoint of the sleep period.[4] A person who goes to bed at midnight and rises at 8 thus has the same chronotype as a person who goes to bed at 1 a.m. and rises at 7; the midpoint of sleep is 4 a.m. for both of these individuals. People with early chronotypes will usually not be able to "sleep in", even if they have stayed up later than usual. While fit for a "lark-like" societal framework, they find it hard to adapt to a context where "sleeping in" is common: ...
Transcriptional repressor which forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. It is derived from the Latin roots circa (about) and diem (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function. Consists of two major components: the central clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and the peripheral clocks that are present in nearly every tissue and organ system. Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers (German for timegivers). The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to
A circadian rhythm /sɜːrˈkeɪdiən/ is any biological process that displays an endogenous, entrainable oscillation of about 24 hours. These 24-hour rhythms are driven by a circadian clock, and they have been widely observed in plants, animals, fungi, and cyanobacteria.[1]
View Notes - Quiz_7 from BIOL 1002 at LSU. Title: Quiz 7 Assign To: BIOL 1002 - 004 Name: DeRoche, Lauren M Due Date: 04/13/2008 Note: Due Date is at midnight. Questions Hormones only stimulate
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Circadian rhythms are affected too. Circadian rhythms are natural metabolic rhythms that occur in virtually all higher organisms. They too are driven by the biological clock so that the organism can anticipate the coming of dawn and dusk and modify its metabolism to be ready for the new conditions. Many metabolic functions are controlled in this way. These include the rhythmic production of melatonin (a sleep hormone) and the diversion of metabolic resources from physical activity during the day, to repair and the immune system at night.. Consequences of losing the circadian rhythm. If the rhythm were to be lost or become weaker due to a failure of the clock as a result of electromagnetic exposure, it would have serious consequences. In humans it would result in tiredness during the day, poor sleep at night, and a reduced nightly production of the sleep hormone melatonin. All of these effects have been reported in people exposed to the radiation from cell towers and other sources of continuous ...
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TY - JOUR. T1 - Drosophila Pacemaker Neurons Require G Protein Signaling and GABAergic Inputs to Generate Twenty-Four Hour Behavioral Rhythms. AU - Dahdal, David. AU - Reeves, David C.. AU - Ruben, Marc. AU - Akabas, Myles H.. AU - Blau, Justin. PY - 2010/12/9. Y1 - 2010/12/9. N2 - Intercellular signaling is important for accurate circadian rhythms. In Drosophila, the small ventral lateral neurons (s-LNvs) are the dominant pacemaker neurons and set the pace of most other clock neurons in constant darkness. Here we show that two distinct G protein signaling pathways are required in LNvs for 24 hr rhythms. Reducing signaling in LNvs via the G alpha subunit Gs, which signals via cAMP, or via the G alpha subunit Go, which we show signals via Phospholipase 21c, lengthens the period of behavioral rhythms. In contrast, constitutive Gs or Go signaling makes most flies arrhythmic. Using dissociated LNvs in culture, we found that Go and the metabotropic GABAB-R3 receptor are required for the inhibitory ...
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Purpose: Sirtuins are a family of NAD-dependent deacetylase that are involved in a variety of cellular functions including metabolism, DNA repair, apoptosis, neuronal survival and inflammation. However, much of the sirtuins in the retina are largely unknown. In this study, we analyzed the mRNA levels of seven sirtuins (Sirt1-7) together with the sirtuin-associated molecules, and the effect of light-dark condition on the expression levels in the retina.. Methods: Six-week-old male C57BL6/J mice were used. The mice were kept under 12-h light/12-h dark (LD) cycle. After keeping under the usual LD cycle for 2 weeks, the mice were randomly divided into the LD group and constant darkness group (DD group). The DD group was transferred to constant darkness after the dark phase of the last LD cycle, and kept in the dark for two 24-hours DD cycles, and then, sacrificed during third 24-hours DD cycle. The retina and the liver of the LD and DD group mice were sampled every 4 hours, and brain parietal ...
TY - JOUR. T1 - Haematopoietic stem cell release is regulated by circadian oscillations. AU - Méndez-Ferrer, Simón. AU - Lucas, Daniel. AU - Battista, Michela. AU - Frenette, Paul S.. PY - 2008/3/27. Y1 - 2008/3/27. N2 - Haematopoietic stem cells (HSCs) circulate in the bloodstream under steady-state conditions, but the mechanisms controlling their physiological trafficking are unknown. Here we show that circulating HSCs and their progenitors exhibit robust circadian fluctuations, peaking 5 h after the initiation of light and reaching a nadir 5 h after darkness. Circadian oscillations are markedly altered when mice are subjected to continuous light or to a jet lag (defined as a shift of 12 h). Circulating HSCs and their progenitors fluctuate in antiphase with the expression of the chemokine CXCL12 in the bone marrow microenvironment. The cyclical release of HSCs and expression of Cxcl12 are regulated by core genes of the molecular clock through circadian noradrenaline secretion by the ...
Circadian rhythms maintain an organisms daily sleep-wake cycle by conserved regulatory pathways, inducing profound effects in metabolic activity. Drosophila circadian period is maintained in a 24-hour cycle with peaks of activity at dawn and dusk. Ethanol exposure causes disruptions in a variety of physiological processes including circadian rhythms. We hypothesized that defects in circadian rhythm might lead to altered behavioral responses to ethanol and to disruptions in ethanol metabolism. To investigate this hypothesis, we used Drosophila strains bearing mutations in the period gene that result in circadian periods which are longer (perL) or shorter (perS) compared to wild type rhythms. We analyzed ethanol metabolism by measuring alcohol dehydrogenase (Adh) activity, an enzyme that converts alcohol to aldehyde, and characterized behavioral responses to ethanol exposure by measuring sedation time, recovery from sedation, and tolerance after repeated exposure. This study will contribute to the
Exercise has many well-established benefits to physical and mental health (25-30). The intensity, duration, frequency, mode, volume, and progression of exercise to optimize the beneficial effects have been well characterized (26, 44, 45). However, the proper timing of exercise and its potential added benefit of improving circadian entrainment have not been investigated thoroughly. Disruption of circadian rhythms (e.g., by shift work, social jetlag, early-morning schedules) is associated with metabolic disorders, cardiovascular disease, and cancer (6-11). If exercise could reduce circadian disruption, then it may also improve the risk factors associated with this disruption.. A tenet of the mammalian circadian system is that it is differentially sensitive to stimuli given at different times of day. Therefore, it is likely that the response of the internal circadian rhythm to exercise depends on the time of day of exercise. We chose morning and evening exercise for 2 reasons. First, morning ...
Dawn phenomenon is the phenomenon which causes a rapid rise or fall in body blood sugar during early morning hours. Dawn phenomenon of diabetes walk common experience seen among diabetics as a result of insulin resisting hormones induced at night time. Lets go deep into the cause of this dawn phenomenon or liver dump effect. Researchers found that the cause of rise and fall in blood glucose level during early morning hours is mainly due to the release of insulin resisting hormones from liver.. Do you know what all are the hormones responsible for causing dawn phenomenon? Cortisol produced from adrenal cortex, glucagons released from alpha cells in pituitary gland, epinephrine formed from outer layer of adrenal glands and growth hormones are some examples of insulin resisting hormones causing dawn phenomenon or high blood sugar in early morning. Release of these hormones during sleep time hours initiates the release of stored energy there by increasing the level of blood glucose level.. As we ...
If these strategies do not work, poor vitamin A status should be considered a possible explanation. This interpretation is strengthened if you have poor night vision (for example, if you strain your eyes or have trouble seeing when driving down an unlit road with your headlights alone but can see fine without any eyestrain during the day) or dry eyes. This interpretation is also strengthened if you have serum retinol near or below the bottom of the reference range, or if you track your vitamin A intake and your daily average is below the RDA.. It is important to note that any of these additional pieces of evidence strengthen the interpretation of poor vitamin A status, but their absence does not rule it out. If circadian rhythm disruption is more sensitive to deficiency than night blindness, then it may occur in the absence of other clinical signs, at serum retinol concentrations within the reference range, and at vitamin A intakes above the RDA.. The best way to ensure basic adequacy of vitamin ...
Free-running sleep is a sleep pattern that is not adjusted (entrained) to the 24-hour cycle in nature nor to any artificial cycle. It occurs as the sleep disorder non-24-hour sleep-wake disorder or artificially as part of experiments used in the study of circadian and other rhythms in biology. Study subjects are shielded from all time cues, often by a constant light protocol, by a constant dark protocol or by the use of light/dark conditions to which the organism cannot entrain such as the ultrashort protocol of one hour dark and two hours light. Also, limited amounts of food may be made available at short intervals so as to avoid entrainment to mealtimes. Subjects are thus forced to live by their internal circadian "clocks". The individuals or animals circadian phase can be known only by the monitoring of some kind of output of the circadian system, the internal "body clock". The researcher can precisely determine, for example, the daily cycles of gene-activity, body temperature, blood ...
Blood pressure drugs should be taken at night.. Uncontrolled blood pressure can lead to heart attacks, paralysis and heart failure. Most such attacks occur in the early morning hours. Pulse, blood pressure and thickening of platelets are all higher in the early morning hours.. Controlling early morning blood pressure can reduce cardiovascular mortality.. According to a study published in the Journal of the American Society of Nephrology, among patients with chronic kidney disease and high blood pressure, taking at least one antihypertensive drug at bedtime significantly improves blood pressure control, with an associated decrease in risk for cardiovascular events.. The study included 661 patients with chronic kidney disease who were randomly assigned either to take all prescribed anti BP drugs on awakening or to take at least one of them at bedtime. Patients were followed for a median of 5.4 years; during that time, patients who took at least one BP-lowering drug at bedtime had approximately one ...
Physically active young adults (M = 14; F = 21) and older adults (M = 12; F = 21) were observed over a period of four to five days following a 90-minute "ultra-short" sleep-wake cycle (30-min sleep, 60-min wake). Baseline circadian rhythm was assessed over 30 hours. During the following three days, Ss were exposed to experimental phase-shifting treatments (randomly assigned exercise or bright light), centered at one of eight randomly assigned times around the 24-hour day. Treatments were one hour of treadmill exercise at 60-70% VO2peak, and three hours of bright light.. It was found that exercise had a similar influence on circadian rhythms as did bright light.. Implication. Regular exercise affects the circadian rhythm.. Return to Table of Contents for this issue.. ...
Keep in mind that the cortisol circadian rhythm described above is the same rhythm experienced by virtually every healthy human being on the planet. This is not true for those who suffer from most forms of exhaustion - including adrenal fatigue. The difficulty for most doctors who try to diagnose adrenal issues, however, is easy to understand: though the patterns in the rhythms are different, the differences between the typical levels of cortisol in a healthy and fatigued individual are not so obvious.. What is usually seen when cortisol is measured over the course of a day is that normal, healthy individuals have cortisol levels that tend to fall within a certain set range at any given point in that twenty-four hour cycle. The average person will usually have cortisol levels that fall somewhere near the middle of that normal range, between the high and low levels at any given moment.. Often times, when doctors measure an adrenal fatigue sufferers cortisol levels, those levels will fall within ...
Eur J Pharmacol. 2009 Mar 15;606(1-3):61-71. doi: 10.1016/j.ejphar.2009.01.029. Epub 2009 Jan 29. Research Support, Non-U.S. Govt
Cold acclimation has been shown to be attenuated by the degradation of the INDUCER OF CBF EXPRESSION1 protein by the E3 ubiquitin ligase HIGH EXPRESSION OF…
The detrimental effects of myocardial infarction in humans and rodents have a 24-h rhythm. In some human cohorts however, rhythmicity was absent, while the time of maximum damage differs between cohorts. We hypothesized that the type of damage influences the 24-h rhythm in infarct size. Myocardial infarction was induced in ... read more 12-week-old C57BL/six mice at four different time-points during the day using either permanent ligation (PL) or 30-min of ischemia followed by reperfusion (IR), with a control group wherein no ligation was applied. Infarct size was measured by echocardiography and histology at a 1-month follow-up. Rhythmicity in infarct size was present in the PL group at the functional and histological level, with maximal damage occurring when the infarct was induced at noon. In the IR group, no circadian rhythm was found. The time of the coronary artery ligation determines the outcome of myocardial infarction. Our data showed that in rodents, the presence of circadian ...
How genes control animal behavior is the big question my lab is interested in. We mainly study circadian (~24hr) rhythms of behavior, arguably the best understood behavior at molecular and cellular levels. We use the fruitfly Drosophila as a powerful model system that has led the way in circadian rhythm research and is ideal for analyzing behavior at the level of single genes, single neurons, neuronal networks and whole animal behavior. We use Genetics, Genomics & BioInformatics, Microscopy and Behavioral assays to build a holistic model of how flies anticipate daily environmental changes.. Adult flies have 24hr rhythms in their activity: they are more active by day, especially at dusk and dawn, and rest by night - paralleling human sleep/wake cycles. These rhythms persist in constant darkness, indicating that flies have an internal sense of time. Forward genetics helped identify a set of core clock genes that are essential for 24hr rhythms in constant darkness, and these genes work together in ...
A circadian rhythm is a 24-hour period affecting the physiology of all living creatures, including plants and animals. While some circadian rhythm functions are governed internally, others are...
Humans, like almost all animals, are phase-locked to the diurnal cycle. Most of us sleep at night and are active through the day. Because we have evolved to function with this cycle, the circadian rhythm is deeply ingrained and even detectable at the biochemical level. However, within the broader day-night pattern, there are individual differences: e.g., some of us are intrinsically morning-active, while others prefer evenings. In this article, we look at digital daily cycles: circadian patterns of activity viewed through the lens of auto-recorded data of communication and online activity. We begin at the aggregate level, discuss earlier results, and illustrate differences between population-level daily rhythms in different media. Then we move on to the individual level, and show that there is a strong individual-level variation beyond averages: individuals typically have their distinctive daily pattern that persists in time. We conclude by discussing the driving forces behind these signature daily
The influence of dosing time on the antitumor effect and the rhythm disturbance effect of melatonin (MLT) was investigated in ICR male mice under a light/dark (12:12) cycle. In tumor-bearing mice, the antitumor effect of MLT (1 mg/kg intraperitoneal) was most effective in the dark phase; and the rhythm disturbance effect of MLT on the locomotor activity was more serious in the light phase than in the dark phase. The antitumor effect and the rhythm disturbance effect of MLT increased when the specific binding of MLT receptor in target tissues, tumor or suprachiasmatic nucleus, increased and they decreased when the level decreased. Furthermore, because luzindole, an MT1 and MT2 blocker, caused the antitumor effect or rhythm disturbance effect of MLT to decrease, it is suggested that the time-dependent change of the pharmacological effects of MLT were influenced by that of MLT receptor(s) function. On the other hand, there was no significant dosing time-dependent change of MLT concentration in ...
Inherent in all living organisms, natures circadian rhythm springs us into activity in the daytime and then into rest and restoration at night. And this circadian rhythm is attuned to the presence and absence of the sun, principally blue light.. Melatonin is critical to regulating the bodys circadian rhythm. When the sun goes down and it becomes dark, our eyes sense the absence of light and send a signal to the brain, which instructs the pineal gland to produce melatonin and put us to sleep.. Now in modern times, the incandescent light began humankinds earliest assault on natures circadian rhythm. This has only worsened with the advent of television, computers, tablets, cell phones, gaming stations and whatever else produces light to interfere with our circadian rhythm. When the lights stay on, melatonin production is slowed or stopped.. Exposure to sunlight - at least 10 to 15 minutes a day is recommended - is also crucial to the production of vitamin D, which is found in very few foods but ...
Light, activity & meals are key inputs to the circadian rhythm. These tools can be used to help managing the circadian rhythm & getting it back in sync.
Kadener, S., J. S. Menet, K. Sugino, M. D. Horwich, U. Weissbein, P. Nawathean, V. V. Vagin, P. D. Zamore, S. B. Nelson, and M. Rosbash. 2009. A role for microRNAs in the drosophila circadian clock. Genes and Development 23, (18): 2179-219. Kadener, S., D. Stoleru, M. McDonald, P. Nawathean, and M. Rosbash. 2007. Clockwork orange is a transcriptional repressor and a new drosophila circadian pacemaker component. Genes and Development 21, (13): 1675-168. Rosbash, M. 2009. The implications of multiple circadian clock origins. PLoS Biology 7, (3): 0421-0425. Shang, Y., L. C. Griffith, and M. Rosbash. 2008. Light-arousal and circadian photoreception circuits intersect at the large PDF cells of the drosophila brain. Proceedings of the National Academy of Sciences of the United States of America 105, (50): 19587-19594. Stoleru, D., P. Nawathean, M. d. l. P. Fernández, J. S. Menet, M. F. Ceriani, and M. Rosbash. 2007. The drosophila circadian network is a seasonal timer. Cell 129, (1): 207-219. ...
Some people may think biological and circadian rhythms are the same as they both refer to bodily periodic fluctuations which impact physical, mental, and
Circadian rhythms are the daily biological and physiological processes that cycle with a period of about 24 hours. In recent years, the circadian field has progressed significantly from the discovery of many genes involved in the core circadian function. The first mammalian circadian gene that was cloned, Clock, was shown to be a transcription factor that is critical for the proper functioning of the circadian system in mammals. Many studies have been conducted with the Clock Δ19 mutation and how ubiquitous perturbations in Clock gene function affect the circadian system at both the behavioral and molecular levels. However, the tissue specific role of the Clock gene in controlling circadian rhythms has not been addressed. In addition, circadian studies have not been conducted with a mouse model that contains a loss of expression of the Clock gene. In this study, we have attempted to address these two issues using a variety of different methods. First, we utilized the tetracycline transactivator ...
Patients who receive more hospital treatment tend to have worse underlying health, confounding estimates of the returns to such care. This paper compares the costs and benefits of extending the length of hospital stay following delivery using a discontinuity in stay length for infants born close to midnight. Third-party reimbursement rules in California entitle newborns to a minimum number of hospital "days," counted as the number of midnights in care. A newborn delivered at 12:05 a.m. will have an extra night of reimbursable care compared to an infant born minutes earlier. We use a dataset of all California births from 1991-2002, including nearly 100,000 births within 20 minutes of midnight, and find that children born just prior to midnight have significantly shorter lengths of stay than those born just after midnight, despite similar observable characteristics. Furthermore, a law change in 1997 entitled newborns to a minimum of 2 days in care. The midnight discontinuity can therefore be used ...
Organisms and even single cells have endogenous biological "clocks" that allow them to tell the time of day. Research in our laboratory is directed towards understanding the cellular and molecular bases of these fascinating timing mechanisms in a variety of organisms: cyanobacteria ("blue-green algae"), plants, and animals. To analyze the molecular nature of the clock in the prokaryotic cyanobacteria, we have developed a bioluminescent reporter strain that expresses a daily rhythm of light emission. Using this bioluminescence rhythm as a marker, clock mutants have been identified. We found that the essential clock gene, KaiC, is rhythmically expressed and forms ATP-dependent hexamers. In collaboration with the laboratory of Dr. Martin Egli, we have crystallized KaiC to determine its three-dimensional structure and discover its phosphorylation sites. The three key bacterial clock proteins (KaiA + KaiB + KaiC) will show circadian oscillations in a test tube! In collaboration with the laboratories ...
In the camel, it has also been demonstrated that the daily Ta cycle is able to entrain the master circadian clock, thus highlighting that Ta is a true zeitgeber (El Allali et al. 2013). The protocol validated in this study will also permit to test in these specific conditions, if the zeitgeber effect of Ta cycle with higher amplitude is able, as suggested by (El Allali et al. 2013), to counteract the zeitgeber effect of the light-dark cycle, a fundamental question in mammalian circadian biology. It will also lead to determine more precisely the functioning of the master clock and the circadian network in dehydrated and heat‐stressed camels.. The use of data loggers over a long period of time has also facilitated understanding the interpretation of (Al‐Haidary 2005). In the present work, we observed that the increase in amplitude of Tb starts after 7 days under heat stress and water deprivation. In the work of (Al‐Haidary 2005), the analysis was only done after 4 days and the protocol used ...
by Vetscite. New research from Colorado State University shows that the function of all genes in mammals is based on circadian - or daily - rhythms. The study, refutes the current theory that only 10 percent to 15 percent of all genes were affected by natures clock. While scientists have long known that circadian rhythms regulate the behavior of the living, the study shows that daily rhythm dominates all life functions and particularly metabolism. The new study presents oscillation as a basic property of all genes in the organism as opposed to special function of some genes as previously believed. Knowing about oscillation properties of genes involved in metabolism is essential for understanding how genes interact with and regulate health and disease. Colorado State University researcher Andrey Ptitsyns new analysis of data collected through several studies establishes a baseline oscillation in 98 to 99 percent of all genes through advanced computer algorithms. Most of these genes have never ...
An in vivo screen of 86 RNAi lines, representing the majority of annotated Drosophila phosphatases/regulators, for altered activity rhythms was carried out. The screen identified a total of 19 candidate genes (Table 1) that altered clock function upon RNAi knockdown in Drosophila clock cells. Further genetic validation of one candidate showed that the RPTP Lar is required for the development of axonal projections from circadian pacemaker neurons that support rhythmic activity in constant darkness but not during light:dark cycles (Agrawal and Hardin 2016).. As expected, a majority of these candidates were not validated upon further analysis of independent genetic reagents (Table 2). However, these reagents consisted of additional P element inserts, where the P element insertion site may not interfere with gene function, or strains that could be used for overexpression, which also may not impact the function of a protein that is already at saturating levels. Therefore, a lack of validation with P ...
We experimentally demonstrated that the technique to stabilize the output signal by harmonic intensities is useful in heterodyne detection with an incoherent light source such as a halogen lamp. The relation between the relative standard deviation of an output signal and the fluctuation of the light intensity is analyzed and simulated. Using the fundamental to sixth harmonics increases the stabilities of output signal approximately 3 times, and subtracting the relative standard deviation of the intensity of light source enhances the stabilities 49 times. The fluctuating phase that is due to the fluctuating frequency and temperature and its power spectrum density for an interferometer is also calculated with the Allan variance.. © 2002 Optical Society of America. Full Article , PDF Article ...
Scientists have shown that disruption of the bodys internal clock system is involved in a range of diseases, from psychiatric to metabolic to cardiovascular. A recent paper by JDRF-funded researcher Joseph Bass, M.D., Ph.D., suggests that it could also be a factor in the development of diabetes. Dr. Bass and his group found that disruption of the circadian rhythm set by the bodys internal clock led to glucose intolerance in mice, raising the possibility that it might have similar effects in people.. The timing of most biological activities-like eating and sleeping-is coordinated with the daily light cycle by the bodys master circadian clock, located in the brain. The master clock communicates with a network of peripheral clocks distributed in tissues and organs throughout the body, including the pancreas. Dr. Basss group previously found that the clock within the pancreas has roles in releasing insulin and normalizing blood-glucose concentration, but the details of how it does this were not ...
EVANSTON, Ill. --- Eat less, exercise more. Now there is new evidence to support adding another "must" to the weight-loss mantra: eat at the right time of day. A Northwestern University study has found that eating at irregular times -- the equivalent of the middle of the night for humans, when the body wants to sleep -- influences weight gain. The regulation of energy by the bodys circadian rhythms may play a significant role. The study is the first causal evidence linking meal timing and increased weight gain.. "How or why a person gains weight is very complicated, but it clearly is not just calories in and calories out," said Fred Turek, professor of neurobiology and physiology in the Weinberg College of Arts and Sciences and director of the Center for Sleep and Circadian Biology. "We think some factors are under circadian control. Better timing of meals, which would require a change in behavior, could be a critical element in slowing the ever-increasing incidence of obesity.". The findings ...
Circadian clocks are found in nearly all organisms, from bacteria to mammals, and ensure that behavioral and physiological processes occur at optimal times of day and in the correct temporal order. It is becoming increasingly clear that chronic circadian misalignment (CCM), such as occurs in shift workers or as a result of aberrant sleeping and eating schedules common to modern society, has profound metabolic and cognitive consequences, but the proximate mechanisms connecting CCM with reduced organismal health are unknown. Furthermore, it has been difficult to disentangle whether the health effects are directly induced by misalignment or are secondary to the alterations in sleep and activity levels that commonly occur with CCM. Here, we investigated the consequences of CCM in the powerful model system of the fruit fly, Drosophila melanogaster. We subjected flies to daily 4-h phase delays in the light-dark schedule and used the Drosophila Activity Monitoring (DAM) system to continuously track locomotor
Researchers at the Yale School of Medicine have found that when and what you eat affects the synchronization of the bodys biological clocks.. Biological clocks, which are found in every cell of the body, operate on a 24-hour cycle, according to a preview of the study written by Gerald Hart, biological chemistry professor at Johns Hopkins University. Synchronizing all the clocks in the body is essential for the body to function at its best. The three-year study, which was conducted on lab mice, found that eating at certain times of the day, which vary depending on ones sleep habits, may lead to optimal body functionality via clock synchronization. The findings were published Feb. 5 in the journal Cell Metabolism.. When food is consumed at the optimal times of the day, the bodys peripheral clocks, which are found in every cell outside the brain, synchronize with the bodys central clock, which is located in the brain and responds to external signals like light and temperature, said researcher ...
a_brandeis_university_study_published_this_week_in_nature_shows_for_the_first_time_that_a_molecular_signal_maintains_coherence_among_brain_clock_cells_that_regulate_daily_activity_of_drosophila_melanogaster_fruit_flies_the_two_key_groups_of_neurons_control_morning_and_evening_activity_and_are_maintained_in_synch_even_when_the_flies_are_plunged_into_darkness_for_extended_periods_of_time_