Circadian rhythms (Space Sciences)

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Vection Is Unaffected by Circadian Rhythms

Vection Is Unaffected by Circadian Rhythms

The endogenous circadian clock also can affect short-term time perception. Pöppel and Giedke (1970) found a diurnal variation of approximately 10 seconds in the time perception of participants who were living according to their normal daily routines (Kuriyama et al., 2003; Morofushi, Shinohara, & Kimura, 2001; Nakajima et al., 1998; Pöppel & Giedke, 1970). In the morning, estimated time was longer than actual time, and in the evening, estimated time was shorter than actual time. Additionally, several studies have found a significant negative cor- relation between estimated time and core body temperature, i.e., participants with a higher core body tempera- ture tend to underestimate the passage of time (Kuriyama et al., 2003; Aschoff, 1984; Aschoff, 1998; Aschoff & Daan, 2009). This indicates that the circadian oscillator might affect short-term time perception through diurnal variation of body temperature. Interestingly, Bougard et al. (2011) reported that the circadian rhythms could af- fect body sway in certain conditions. As body sway and vection are thought to be highly related (Palmisano et al., 2014), a relationship between vection and the circadian rhythms seems likely.
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Regulation of Sleep and Circadian Rhythms by Metabolic Neuropeptides

Regulation of Sleep and Circadian Rhythms by Metabolic Neuropeptides

Greenspan, 2007; C He et al., 2013; Lingo et al., 2007; Q. Wu, Zhao, et al., 2005). NPF is expressed in neurons in the brain and endocrine cells in the midgut, although the role of NPF in the midgut is not understood (Brown et al., 1999; Nässel & Wegener, 2011). In the brains of male flies, NPF is expressed in a subset of circadian neurons; however only recently has there been any evidence of a functional role for NPF in the circadian system (G. Lee et al., 2006). Ablation of NPF-positive neurons slightly lengthens the free-running circadian period and knockdown of npf or the npf receptor (npfr) modulates rest:activity rhythms under light:dark conditions (C He et al., 2013; Hermann et al., 2012). NPF is related to the vertebrate Neuropeptide Y (NPY), which has been associated with circadian rhythms as a mediator of non-photic circadian entrainment (Besing et al., 2012; Maywood, Okamura, & Hastings, 2002; Yannielli & Harrington, 2004). Mutant mice lacking NPY display rhythmic behavior, but do not adapt to phase shifts as efficiently as controls (Harrington et al., 2007). Although both NPY and NPF appear to play only minor roles in regulating rhythmic locomotor behavior, it is not known whether these peptides play important roles in other aspects of circadian rhythms, such as circadian control of energy homeostasis.
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According to current belief, molecular circadian rhythms in

According to current belief, molecular circadian rhythms in

Previous experiments with mice and rats have shown that circadian feeding cycles are important Zeitgebers for the syn- chronization of circadian oscillators in peripheral organs, such as liver and kidney (10–12). We thus considered it interesting to examine the expression of circadian clock and clock-controlled genes in the SCN and in peripheral organs of the strongly ultradian vole and compare it with that of the mouse. Our results show that clock-gene expression in the SCN of voles undergoes similarly strong circadian rhythms as those reported for mice (e.g., refs. 10, 11, 19, and 20). In contrast, peripheral circadian oscillations in the vole are either not synchronized or absent, unless they are induced by restricted feeding or housing condi- tions that promote circadian behavior. Different mechanisms could account for the nearly constant expression of circadian clock genes in peripheral organs of voles with ultradian behavior and feeding rhythms. It remains formally possible that the expression of clock genes oscillates with ultradian rhythms (entrained to activity rhythms) in the liver and kidney of voles. Obviously, even if these short-period rhythms were synchronized within and between animals, the 4-hour resolution of our temporal mRNA recordings would have been insufficient to uncover such ultradian cycles. Nevertheless, given that periph- eral vole tissues do contain circadian oscillators, we consider it more likely that these dampen or become desynchronized in the absence of circadian feeding and 兾 or activity cycles acting as the Zeitgeber. If peripheral oscillators were desynchronized in voles with ultradian behavior but synchronized by imposed feeding rhythms, the total accumulation of clock-gene transcripts over a day should be similar in rhythmic and arrhythmic livers. The data presented in Fig. 6 are roughly compatible with this prediction. However, these data would also fit a scenario in which all oscillators are arrested at a phase at which
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Drugs of Abuse Can Entrain Circadian Rhythms

Drugs of Abuse Can Entrain Circadian Rhythms

drug injection time, but in the absence of the drug injection, suggested the possibility that the locomotor activity previously elicited by the drug might have acted as a circadian zeitgeber, entraining one or both of the pre- and postinjection running activity. To test this possibility, we again gave rats a series of MA injections spaced at 24-h intervals, but this time we confined them to a small cage within the circadian chamber for 5 h immediately following the drug administrations to prevent gross locomotor activity. The same rats were then given a second series of 20 daily injections at a different time, while allowing free access to the wheel. Anticipatory wheel running developed normally in both cases and did not appear to differ in amount (Fig. 2). Thus, intense bouts of postdrug gross motor behavior do not appear to be required for the entrainment or expression of anticipatory drug-related circadian rhythms, although some combination of gross motor behavior and its accompaniments appears to affect rhythms following drug injection.
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A stochastic model for circadian rhythms from coupled ultradian oscillators

A stochastic model for circadian rhythms from coupled ultradian oscillators

The third time scale is, of course, the circadian rhythm time scale, which in our model arises from an interaction of two of the simpler ultradian oscillators of slightly dif- ferent frequencies. Natural selection could explain why pairs of frequencies leading to the right "beats" have emerged in the course of evolution. In fact, the common occurrence of ultradian oscillators would make it easy for evolution to produce circadian rhythms out of different components in different organisms, as is actually observed [4]. This mechanism has the added advantages of robustness and easy adaptability (the period of the beat will change with minor adjustments of the frequency ratio between the two primary oscillators, but this ratio could stay quite stable even if the parameters involved varied with external conditions such as temperature). A power spectrum analysis presented below demonstrates the robustness of the model with respect to the parameter ε . We mention that power spectra could be used to analyze observational data for a potential validation of the model. First steps in this direction were taken in [12].
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The role of race and ethnicity in sleep, circadian rhythms and cardiovascular health

The role of race and ethnicity in sleep, circadian rhythms and cardiovascular health

Considering the substantial evidence of racial/ethnic differences in both studies of sleep and circadian rhythms and in studies of CVD risk, here we present the arguments why sleep and circadian rhythms may be mediating the racial/ethnic disparities in CVD. One cornerstone of such an argument is that coincident differences in circadian rhythm and CVD have been found in specific races/ethnicities. The timing of myocardial infarction (MI) has been found to be ethnicity dependent across Indo-Asians and Mediterranean Europeans. A significantly higher number of acute MI onset occurred between midnight and noon in white and Indo-Asian individuals in the UK). In contrast, Mediterranean Europeans showed the converse pattern, with most of the acute MI events happening between noon and midnight [85]. Similar coincident racial/ethnic differences in cardiovascular function and circadian rhythms have been found elsewhere: African-Americans are more likely to be non- dippers (<10% drop in systolic pressure during sleep) compared to European-Americans, and this difference was exacerbated in night shift workers, suggesting that different race/ethnicities may be differentially impacted by circadian misalignment [86].
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The relevance of microRNAs and circadian rhythms in drug safety

The relevance of microRNAs and circadian rhythms in drug safety

Circadian (derived from latin, circa diem) rhythms are defined at rhythms in biological or biochemical events that have a periodicity of approximately 24 hours. Circadian rhythms are distinct from other biological rhythms such as ultradian rhythms (biological rhythms with a periodicity less than 24 hours, e.g. 90 minute cycles of R.E.M. sleep) and infradian rhythms (biological rhythms with a periodicity longer than 24 hours, e.g. menstruation cycles). Many intrinsic physiological processes exhibit a daily cyclic pattern, e.g. heart rate, blood pressure, body temperature and metabolism all show time-of-day differences in their level or activity. This is considered to confer an advantage to organisms to allow anticipatory rather than reactionary behaviour to stimuli such as food availability (Gehring & Rosbash, 2003). Circadian rhythms are observed throughout nature; plants, animals and bacteria show 24- hour rhythms in their biology. Furthermore, in man, it is accepted that the wellbeing of individuals is dependent on functioning and unperturbed circadian biology. For example, studies have shown that rotating shift workers are at more risk of developing cancer and cardiovascular disease due to a constantly disrupted circadian system (Schernhammer et al, 2001, Boggild & Knutsson, 1999). Furthermore, there is a strong link between sleep disorders and other morbidities such as metabolic syndrome and depression (Ford & Kamerow, 1989, Punjabi & Polotsky, 2005). This growing body of evidence suggests that the effects of circadian regulation are extensive on core physiology.
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Short Sleep Duration and Circadian Rhythms: Association with Suicidal Behaviour

Short Sleep Duration and Circadian Rhythms: Association with Suicidal Behaviour

Genetic factors have also been suggested, such as alterations in the CLOCK genes regulating sleep circadian rhythms. In this context, Benedetti et al. [47] showed that the CLOCK gene rs181260*C polymorphism conditioned not only sleep phase delays, but also an increased risk for suicide attempts (most likely interacting with a previous experience of stressful events, making the individuals more sensitive to it). If this gene is involved in the presence of a sleep phase delay and also somehow influences the development of suicidal behaviours, these disorders could be connected. Two mechanisms were proposed by the authors: 1) the clock gene machinery could control circadian gene expression and responsivity to stimuli at cellular level, modulating the activity of brain structures that control emotions and behaviour; 2) rs1801260*C genotype is associated to sleep phase delay and insomnia, which are in turn associated with suicide in the general population – thus, the effect on sleep delay could mediate the influence of this gene on depression and suicide.
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Circadian Rhythms and Seasonal Incidence of Cardiac Arrhythmia in Cardiovascular Patients

Circadian Rhythms and Seasonal Incidence of Cardiac Arrhythmia in Cardiovascular Patients

As regards the other cardiovascular incidents, numerous results were obtained in relation to circadian rhythms. In some studies, no peak incidence of myocardial infarction was reported (25) while in the others the peak time of myocardial infarction attacks was observed in the morning hours (26,27). Stimulating the internal process (i.e., increased adrenergic activity, blood pressure, heart rate, platelet adhesion, and the like) after waking and beginning of physical activities and mental stress are indicated as the possible causes of these incidents. Additionally, Salehian et al emphasized the effect of activity and mental stress on the time of attack (25). In addition, Dianati et al examined the effect of physical activities on the incidence of MI during different times of the day. Further, they investigated the impact of such activities on internal circadian rhythm in ischemic patients. Based on the results, a morning-time increase and an evening-time reduction were observed in MI pain with increased and decreased physical and mental activities, respectively (28). These results demonstrated that identifying the circadian rhythm played an important role in preventing the occurrence of MI.
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Barley Hv CIRCADIAN CLOCK ASSOCIATED 1 and Hv PHOTOPERIOD H1 Are Circadian Regulators That Can Affect Circadian Rhythms in Arabidopsis

Barley Hv CIRCADIAN CLOCK ASSOCIATED 1 and Hv PHOTOPERIOD H1 Are Circadian Regulators That Can Affect Circadian Rhythms in Arabidopsis

Since both the photoperiodic-sensitive and–insensitive alleles of Hv-Ppd1 were able to com- plement the prr7-11 phenotype, this suggested that the causative SNP affects photoperiodism independent of circadian rhythms. To test this directly, circadian rhythms of gas exchange from a Triumph (ppd-H1) H. vulgare line were compared to those from the same line into which the Igri Ppd-H1 allele had been introgressed and it was found that the circadian period was not significantly altered between barley plants carrying the Hv-Ppd1 and Hv-ppd1 alleles. Whilst mutation in HvPpd-H1 did not produce detectable effects on circadian function either in barley or through complementation tests in Arabidopsis Atprr-11, the Hvppd-H1 allele does abolish circadian rhythms of photoperiodic-response and vernalisation-response genes HvCO1, HvCO2 and Vrn-H1 [12]. These findings coupled with our demonstration that both HvPpd1-H1 and Hvppd-H1 can complement AtPrr7-11 suggest that HvPpd-H1 has at least two regulatory roles, one required for proper functioning of the circadian system, and one required for generation of rhythmic outputs, and it is the latter that is compromised in Hvppd-H1.
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Wavelet spectral testing : application to nonstationary circadian rhythms

Wavelet spectral testing : application to nonstationary circadian rhythms

Nematode dataset. This dataset was obtained using male Caenorhabditis ele- gans strain PE254 (obtained from the CGC), which expresses firefly luciferase under the promoter of the sur-5 gene (feIs4 [Psur-5::luc+::gfp; rol-6(su1006)] Lagido et al. (2008)). Nematodes expressing luciferase driven by the sur-5 promoter have previously been reported to show circadian rhythms in luminescence (Goya et al., 2016). Single nematodes were placed in wells containing 100µl S buffer (Stiernagle, 1999), supplemented with 5 mg/mL cholesterol, 1 g/L wet weight pelleted Escherichia coli OP50 strain and 100 µM luciferin. Treatment wells also contained 10 µM SB 203580 (a p38 MAPK inhibitor (Sigma S8307)). Entrainment conditions were 12 hours at 20 ◦ C followed by 12 hours at 15 ◦ C for two days in constant darkness. Free-running was at 20 ◦ C in constant darkness. Luciferase measurements were recorded approximately every 13 minutes. Nematodes that died (shown by a sudden loss of luciferase expression) were excluded from data analysis. Therefore, this dataset consists of 62 signals recorded at T = 512 time points, with the ‘Control’ and ‘Treatment’ groups containing 32 and 30 time se- ries respectively.
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Circadian Rhythms in Neurospora crassa and Other Filamentous Fungi

Circadian Rhythms in Neurospora crassa and Other Filamentous Fungi

As already suggested, one goal of studying the circadian clock in model organisms is to determine if the properties of the clock in one organism are conserved in other organisms. Eventually, such conserved features will likely provide impor- tant clues for the function of the human clock and provide ideas for therapies for clock dysfunction. As one step towards this goal, circadian clocks were investigated in two other spe- cies of filamentous fungi that are easily cultured in the labo- ratory and whose genomes are sequenced, i.e., Aspergillus fla- vus and Aspergillus nidulans (38, 42). In A. flavus, the clock was shown to control daily rhythms in the development of sclerotia, which are large survival structures produced by many fungi. This developmental rhythm exhibits all of the principal clock properties: the rhythm is maintained under constant environ- mental conditions, with a period of about 30 h at 30°C, it can be entrained by environmental signals, and it is temperature compensated. Interestingly, this endogenous 30-h period is one of the longest natural circadian rhythms reported for any or- ganism, and this likely contributes to some unique responses of the clock to environmental signals. In A. nidulans, no obvious rhythms in development were observed. However, a free-run- ning and entrainable rhythm in the accumulation of gpdA mRNA (encoding glyceraldehyde-3-phosphate dehydroge-
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The Application and Challenges of RNA-Sequencing to the Study of Circadian Rhythms

The Application and Challenges of RNA-Sequencing to the Study of Circadian Rhythms

expression of key mediators of physiology and behavior. Here we apply a combined approach using high resolution temporal profiling by DNA arrays with lower resolution temporal profiling by RNA sequencing to profile clock regulated gene transcription in mouse liver. This hybrid approach allows us to leverage array data to identify oscillating transcripts with a high degree of accuracy, and then explore the structure and splicing patterns of these transcripts. Analysis of this data demonstrates the importance of sampling resolution when designing experiments to identify oscillating transcripts. Furthermore, we show that more than half of core clock factors express alternatively spliced forms concurrently in mouse liver. Interestingly, we find several forms of non- coding RNAs, including microRNAs and long non-coding RNAs, exhibit high amplitude circadian rhythms. These results provide a more complete picture of circadian
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A comparison of high-throughput techniques for assaying circadian rhythms in plants

A comparison of high-throughput techniques for assaying circadian rhythms in plants

Interestingly, in recent years the sensitivity of lumines- cence imaging cameras has increased to the point where more specific resolution is now possible. In the duck- weed Lemna gibba, circadian rhythms in AtCCA1:LUC+ have been detected within individual cells following tran- sient transformation by particle bombardment [46]. In Arabidopsis, tissue-specific clocks have been identified in the leaf mesophyll and vasculature through the use of split-luciferase assays, wherein half of the luciferase pro- tein is driven by a clock promoter and another half by a tissue-specific promoter, which are only luminous when expressed together in the same cell [47]. However, whilst luciferase has been used successfully to assay clock func- tion in various species, most notably tobacco, arabidop- sis [35] and rice [48], the need to introduce transgenic luciferase into the plants is a time-consuming step that greatly reduces throughput and renders the system unsuit- able for species without a transformation protocol. Whilst currently transgene expression is dependent on promoter activity and the genomic context of the random transgenic insertion, in the future and through the use of precision genome engineering techniques [49] we are likely to see luciferase being fused directly to endogenous genes within the native context.
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Circadian Rhythms and Energy Metabolism Reprogramming in Parkinson's Disease

Circadian Rhythms and Energy Metabolism Reprogramming in Parkinson's Disease

Changes in entropy production rates are associated with metabolic and thermodynamic alterations and abnormal circadian rhythms in NDs. In PD, the canonical WNT/β-catenin pathway is down- regulated, while PPARγ is upregulated. These two systems act in an opposed and reverse manner. From a thermodynamic point of view, ND processes are like many irreversible processes which can occur by changing the entropy production rate. Thermodynamic behaviors of metabolic enzymes in PD are modified by the dysregulation of both the canonical WNT/β-catenin pathway and PPARγ expression. Downregulation of WNT/β-catenin pathway results in inhibition of c-Myc, HIF-1α, PDK, LDH-A, and MCT-1. This explains the glucose hypometabolism and the stimulation of oxidative stress observed in PD cells. In parallel, PPARγ interfere with the mammalian clock and energy metabolism and could be a promising therapeutic way in PD due to these interactions. PD processes may be considered as dissipative structures, which exchanges energy or matter with their environment. WNT pathway and PPARγ are open systems, far- from the thermodynamic equilibrium that operate under non-linear regime evolving to non-stationary states. Far-from-equilibrium thermodynamics are notions driven by circadian rhythms. Indeed, CRs directly contribute to regulation of the molecular pathways WNT/β-catenin pathway and PPARγ involved in the reprogramming of cellular energy metabolism enabling Parkinson's disease.
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Heat the Clock : Entrainment and Compensation in Arabidopsis Circadian Rhythms

Heat the Clock : Entrainment and Compensation in Arabidopsis Circadian Rhythms

The circadian clock is a biological mechanism that permits some organisms to anticipate daily environmental variations. This clock generates biological rhythms, which can be reset by environmental cues such as cycles of light or temperature, a process known as entrainment. After entrainment, circadian rhythms typically persist with approximately 24 hours periodicity in free-running conditions, i.e. in the absence of environmental cues. Experimental evidence also shows that a free-running period close to 24 hours is maintained across a range of temperatures, a process known as temperature compensation. In the plant Arabidopsis, the e ect of light on the circadian system has been widely studied and successfully modelled mathematically. However, the role of temperature in periodicity, and the relationship between entrainment and compensation, are not fully understood. Here we adapt recent models to incorporate temperature dependence by applying Arrhenius equations to the parameters of the models that characterize transcription, translation, and degradation rates. We show that the resulting models can exhibit thermal entrainment and temperature compensation, but that these phenomena emerge from physiologically di erent sets of processes. Further simulations combining thermal and photic forcing in more realistic scenarios clearly distinguish between the processes of entrainment and compensation, and reveal temperature compensation as an emergent property which can arise as a result of multiple temperature-dependent interactions. Our results consistently point to the thermal sensitivity of degradation rates as driving compensation and entrainment across a range of conditions.
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The Regulation of Sleep and Circadian Rhythms: The Role of Melatonin and Adenosine in Zebrafish

The Regulation of Sleep and Circadian Rhythms: The Role of Melatonin and Adenosine in Zebrafish

Figure 2.9. Melatonin is required for the circadian regulation of sleep (Related to Figure 2.8) (A-J) Graphs are based on data shown in Figures 7A-7C. (A, B) WT and heterozygous mutants raised in LD and tested in DD maintain locomotor activity and sleep circadian rhythms, but aanat2-/- larvae lack sleep circadian oscillations. Black and hatched boxes indicate subjective night and day, respectively. aanat2-/- larvae exhibit slightly fewer sleep bouts (D), shorter sleep bouts (F), more locomotor activity (H) and longer wake bouts (J) during subjective night. Similar but generally weaker phenotypes are observed during subjective day (C, E, G, I). Data are from one representative experiment (A, B) or combined from three (C-J) experiments. Bar graphs represent median ± MAD (C, D) and mean ± SEM (E-J). *, p<0.05; **, p<0.01 compared to aanat2-/- by Steel-Dwass (C, D) or Dunnett’s test (E-J). (K, L) aanat2-/- and WT larvae raised in LD maintain circadian rhythms in DD (LDDD). WT (red) and aanat2-/- (blue) larvae were raised in LD and shifted to DD at 11 pm on the fourth night of development. Samples were collected at 6-hour intervals from 6 pm on day 5 until 6 pm on day 6. The expression of per1b (K) and arntl1a (L) oscillates for both WT and aanat2-/- larvae (peak:trough ratio is 16 for WT and 22 for aanat2-/- for per1b, and 4.3 for WT and 3.7 for aanat2-/- for arntl1a). 24 larvae were pooled for each sample and the mean ± SEM of triplicate samples at each time point is shown.
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Wavelet spectral testing : application to nonstationary circadian rhythms

Wavelet spectral testing : application to nonstationary circadian rhythms

Nematode dataset. This dataset was obtained using male Caenorhabditis ele- gans strain PE254 (obtained from the CGC), which expresses firefly luciferase under the promoter of the sur-5 gene (feIs4 [Psur-5::luc+::gfp; rol-6(su1006)] Lagido et al. (2008)). Nematodes expressing luciferase driven by the sur-5 promoter have previously been reported to show circadian rhythms in luminescence (Goya et al., 2016). Single nematodes were placed in wells containing 100µl S buffer (Stiernagle, 1999), supplemented with 5 mg/mL cholesterol, 1 g/L wet weight pelleted Escherichia coli OP50 strain and 100 µM luciferin. Treatment wells also contained 10 µM SB 203580 (a p38 MAPK inhibitor (Sigma S8307)). Entrainment conditions were 12 hours at 20 ◦ C followed by 12 hours at 15 ◦ C for two days in constant darkness. Free-running was at 20 ◦ C in constant darkness. Luciferase measurements were recorded approximately every 13 minutes. Nematodes that died (shown by a sudden loss of luciferase expression) were excluded from data analysis. Therefore, this dataset consists of 62 signals recorded at T = 512 time points, with the ‘Control’ and ‘Treatment’ groups containing 32 and 30 time se- ries respectively.
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Significance of circadian rhythms in severely brain-injured patientsA clue to consciousness?

Significance of circadian rhythms in severely brain-injured patientsA clue to consciousness?

and closer to the times of the CRS-R assessments in these cases, thereby underlining the potential clinical usefulness of BLS. Even more importantly, we can speculate that a prespecified temperature rhythm could be useful in guiding the time of assessment of patients, thereby decreasing the risk of misdiagnoses, and we propose that it may be advantageous if assess- ments took place around the time of occurrence of the temperature maximum. Future studies should specifically test this hypothesis, i.e., that behavioral performance improves the closer to the temperature maximum the assessment takes place. Beyond this, the variability in the times when patients’ body tempera- ture was maximal (figure e-2) may further underline the significance of light/dark cycles on DOC patients. While light levels were generally low (,500 lux, fig- ure e-1), patients varied in the amount of time their eyes were closed and ambient light levels were modu- lated by, e.g., weather conditions. Although very low light levels (1.5 lux) have been shown to be sufficient to entrain circadian rhythms in healthy individuals, 38
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Circadian rhythms in the three-dimensional genome: implications of chromatin interactions for cyclic transcription

Circadian rhythms in the three-dimensional genome: implications of chromatin interactions for cyclic transcription

Circadian rhythms orchestrate crucial physiological functions and behavioral aspects around a day in almost all living forms. The circadian clock is a time tracking system that permits organisms to predict and anticipate periodic environmental fluctuations. The circadian system is hierarchically organized, and a master pacemaker located in the brain synchronizes subsidiary clocks in the rest of the organism. Adequate synchrony between central and peripheral clocks ensures fitness and potentiates a healthy state. Conversely, disruption of circadian rhythmicity is associated with metabolic diseases, psychiatric disorders, or cancer, amongst other pathologies. Remarkably, the molecular machinery directing circadian rhythms consists of an intricate network of feedback loops in transcription and translation which impose 24-h cycles in gene expression across all tissues. Interestingly, the molecular clock collaborates with multitude of epigenetic remodelers to fine tune transcriptional rhythms in a tissue-specific manner. Very exciting research demonstrate that three-dimensional properties of the genome have a regulatory role on circadian transcriptional rhythmicity, from bacteria to mammals. Unexpectedly, highly dynamic long-range chromatin interactions have been revealed during the circadian cycle in mammalian cells, where thousands of regulatory elements physically interact with promoter regions every 24 h. Molecular mechanisms directing circadian dynamics on chromatin folding are emerging, and the coordinated action between the core clock and epigenetic remodelers appears to be essential for these movements. These evidences reveal a critical epigenetic regulatory layer for circadian rhythms and pave the way to uncover molecular mechanisms triggering pathological states associated to circadian misalignment.
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