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Outputs of cosinor analysis did not differ between Cosinor.Online, MATLAB code and R packages, cosinor and cosinor2. Details of the analyzes are available at https://bit.ly/CosinorOnlineExamples . Amp -amplitude; Acr -acrophase (peak or trough; hours, decimal form).
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Physiological processes oscillate in time. Circadian oscillations, over approximately 24-h, are very important and among the most studied. To evaluate the presence and significance of 24-h oscillations, physiological time distributed data (TDD) are often set to a cosinor model using a wide range of irregularly updated native apps. If users are fami...
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... 2019; quick analysis of periodic data, but we are open to any suggestions for how to improve the application based on user experiences and this information can be shared in the tab Suggestions, questions . Mesor, amplitude, acrophase and the significance of the estimated model were the same using different applications and Cosinor.Online (Table 1) . 18, 2019; analysis, which can detect significant 24-h variability. ...Context 2
... 2019; quick analysis of periodic data, but we are open to any suggestions for how to improve the application based on user experiences and this information can be shared in the tab Suggestions, questions . Mesor, amplitude, acrophase and the significance of the estimated model were the same using different applications and Cosinor.Online (Table 1) . 18, 2019; analysis, which can detect significant 24-h variability. ...Similar publications
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Citations
... Before starting the experiment, the mice were acclimated to the LD cycle for 2 weeks to eliminate the effects of environmental changes on the experimental results. Cosine curves were fitted to repeated measures activity and meal data using the cosinor method, and the characteristics of the curves were then calculated (Molcan, 2019). ...
Circadian rhythm disturbances are the most common symptoms during the early onset of AD. Circadian rhythm disorders aggravate the deposition of amyloid plaques in the brains of AD patients. Therefore, improving the circadian rhythm of AD patients might slow down the pathological development of neurodegeneration. Circadian regulation is driven by a master clock in suprachiasmatic nuclei (SCN) and peripheral clock located in peripheral organs. The rhythmic feeding–fasting cycle has been proved to dominant cue to entrain peripheral clocks. We hypothesized that dietary intervention to a certain period of time during the dark phase might entrain the clock and reset the disrupted daily rhythms of AD mice. In this study, exogenous glucagon-like peptide-1 (GLP-1) treatment, time-restricted feeding (TRF), and the combination were used to examine the effect of overall circadian rhythm and neurodegenerative pathogenesis of transgenic AD mice. It was confirmed that GLP-1 administration together with time-restricted feeding improves circadian rhythm of 5 × FAD mice including the physiological rhythm of the activity–rest cycle, feeding–fasting cycle, core body temperature, and hormone secretion. Furthermore, GLP-1 and TRF treatments improved the diurnal metabolic homeostasis, spatial cognition, and learning of 5 × FAD mice. The aberrant expression of clock genes, including Baml1 , Clock, and Dbp , was improved in the hypothalamus, and pathological changes in neurodegeneration and neuroinflammation were also observed in AD mice with dual treatment.
... Circadian rhythms in VM were graphed by fitting the time-series measurements of each lamb to the cosine curve of a 24-h activity rhythm, which was obtained by the cosinor method at the Cosinor on-line platform (Molcan 2019). Midline Estimating Statistic of Rhythm (MESOR, the average around which the variable oscillates), amplitude (the difference between the peak and the mean value of a wave), and acrophase (the time of peak activity) were calculated for each variable for each individual. ...
Twenty-two lambs were used to determine their locomotor activity during lactation, and its circadian rhythm, based on data collected by actigraphy; the relationships among lambs were also measured calculating their proximity and distance. Lambs were fitted with Bluetooth-enabled (BT) accelerometers during weeks 1 and 4 of age, and data were downloaded as activity counts at 1-min intervals (Vector Magnitude, VM). Sensors were programmed as receivers and as beacons of the BT signal to calculate proximity (min/h) and distance (m) to another lamb. For each week, mean daily VM was calculated at hourly intervals. Circadian rhythms in VM were graphed by fitting the time-series measurements of each lamb to the cosine curve of a 24-h activity rhythm. Week of lactation and lamb sex had a significant (P < .05) effect on VM. Lambs had a higher (P < .05) VM (counts/min ±S.E.) in week 1 (154 ± 13) than in week 4 (117 ± 4), and female (113 ± 10) were more active (P < .01) than male lambs (113 ± 10). Twin lambs spent more time (P < .001) close to its sibling than to another lambs. Lamb activity followed a 24-h rhythm in week 4, only. In conclusion, actigraphy demonstrated that circadian rhythms in activity were not present in the first week of life, and twin-born lambs had stronger associations with their littermates than did singletons with other lambs, which reflected the strong bond that is established between twin lambs.
... Daily rhythmicity of all mRNA expressions and hormone levels were evaluated by unimodal cosinor regression analysis using Cosinor online application. bioRxiv, 805,960 [37]. Statistical significance was accepted at P ≤ 0.05. ...
Coordination between central and peripheral reproductive clocks in females is poorly understood. Long light is having a hazardous effect on reproductive health. Hence, explored the effect of long-time light exposure (LLD; 16L:8D) on the central and peripheral reproductive (ovary and uterus) clock genes (Bmal1, Clock, Per1, Per2, Cry1 and Cry2) and its downstream regulators (Aanat, Egf, Cx26, Cx43, ERα, pAktS-473, pAktT-308, pFoxO1T-24, 14–3-3, HoxA10, HoxA11 and Pibf) expression in non-pregnant and pregnant Golden hamster. Young adult Golden hamsters were exposed to LLD for 30 days and then were mated. We observed that LLD exposure increased the thickness of the endometrium and reduced myometrium thickness, resembling uterine adenomyosis. In non-pregnant females LLD altered the expressions of clock genes in suprachiasmatic nuclei (SCN), ovary and the uterus along with serum estradiol rhythm. LLD upregulated Egf and downregulated Aanat, Cx26, and Cx43 mRNA levels in uterus. LLD upregulated Akt/FoxO1 phosphorylation and 14-3-3 expressions in the uterus of nonpregnant females. LLD exposure to pregnant females lowered serum progesterone, Aanat, Pibf, Hoxa10, and Hoxa11 mRNA expressions on D4 (peri-implantation) and D8 (post-implantation) resulting in a low implantation rate on D8 (post-implantation). Hence it is evident that the frequent pregnancy anomalies noted under a long light schedule might be due to desynchronization in Aanat, Pibf, Hoxa10, and Hoxa11 as well as the central and peripheral clock genes (Bmal1, Clock, Per1, Per2, Cry1 and Cry2). LLD exposure desynchronized the central and peripheral reproductive clock affecting uterine physiology via Akt/FoxO1 pathway in Golden hamsters. Thus, LLD is a risk factor for female reproductive health and fertility.
... Monthly circadian rhythmicity in sheep activity was graphed following the method described by Palacios et al. (2021). The time-series speed estimates were fitted to the cosine curve of a 24-h activity rhythm, which was obtained from the cosinor method at the Cosinor online platform (https://cosinor.online/app/cosinor.php) (Molcan, 2019). The three variables derived from the cosine curve adjustment were the midline estimating statistic of rhythm (MESOR), which is the average value around which the variable fluctuates, the amplitude (A), which is the difference between a wave average value and its peak and the acrophase (ϕ), which is the time at which the highest activity occurs. ...
GPS collars are a technology that is used extensively to monitor livestock due to its versatility. In this study, the main objective was to confirm whether it can detect the circadian rhythmicity that modulates the behavior of free-grazing sheep. The Churra-breed flock that was monitored grazed an approx. 166-ha fenced area within a dehesa ecosystem in the northwestern Iberian Peninsula. Geolocations were recorded every 30 min for two years. Animal activities were categorized based on the speed; an animal was “moving” if the speed was > 0 m/s (the analyzed category), and “resting” if the speed was 0 m/s. Sheep grazing activity in terms of their speed, azimuth, and distance traveled, was subjected to a circadian adjustment derived from the Cosinor tool online. Results reveal that the flock activity, whether based on speed, distance traveled, or azimuth, fit a circadian rhythmicity (p<0.05). In the summer, particularly July and August, sheep exhibited a significant advance in the acrophase (the time at which the peak of a rhythm occurs), which might have been caused by day length and temperature. In all seasons, flock activity was significantly higher in the diurnal period, while the lowest activity was found in all cases at night, although in the summer sheep activity was high at dawn. In addition, in the day, sheep activity was significantly higher in the fall than it was at other times of the year. The preferred grazing direction of the sheep was non-random, since it was modulated by the contour orientation and the limits of the grazing area. It could be concluded that GPS geolocations allow to demonstrate that free-grazing sheep activity is modulated by a circadian rhythmicity.
... The sGPSC frequency, the synaptic charge transfer data, and the I tonic amplitude were plotted versus the zeitgeber time of recording and analyzed with the Cosinor. Online calculator (https://cosinor.online/app/cosinor.php) to identify diurnal changes (47). The Pearson's correlation coefficient was calculated with the ggscatter() function in the ggpubr library (0.4.0) running in RStudio (version 1.2.5033). ...
Synaptic and extrasynaptic GABA A receptor (GABA A R)-mediated neurotransmission is a critical component of the suprachiasmatic nucleus (SCN) neuronal network. However, the properties of the GABA A tonic current (I tonic ) and its origin remain unexplored. Spontaneous GABA A postsynaptic currents (sGPSC) and I tonic were recorded from SCN neurons using the whole-cell voltage-clamp technique at different times of the day. GABA A R antagonists (bicuculline, gabazine, and picrotoxin) inhibited sGPSC and induced an outward shift of the holding current, which defined the I tonic amplitude. The sGPSC frequency, synaptic charge transfer, and the I tonic amplitude all demonstrated significant diurnal rhythms with peaks in the middle of the day (Zeitgeber Time, ZT8) and nadirs at night (ZT19). The I tonic amplitude increased proportionally with the sGPSC frequency and synaptic charge transfer during the day and required action potential-mediated GABA release, which was confirmed by TTX application. The activation of presynaptic GABA B receptors by baclofen did not significantly alter the I tonic of neurons with low-frequency sGPSC. The equilibrium potential (Eq) for I tonic was similar to the Eq for chloride and GABA A receptor-activated currents. I tonic showed outward rectification at membrane potentials over the range of -70 mV to -10 mV, then was linear at voltages greater than -10 mV. GABA A R containing α4-, α5- and δ- subunits were expressed in SCN, and their contribution to I tonic was confirmed by application of the GABA A R agonist THIP and the GABA A R inverse agonist L655,708. Thus, the I tonic was mediated by extrasynaptic GABA A Rs activated predominantly by GABA diffusing out of GABAergic synapses.
... The 5-min observations records of each variable were grouped hourly, and recoded for day and night times. Circadian rhythms in T, HR, and ACT were graphed by fitting the time series measurements of each cow to the cosine curve of a 24-h activity rhythm, which was obtained by the cosinor method at the Cosinor on-line platform (Molcan, 2019). 1 Midline Estimating Statistic of Rhythm (MESOR, the average value around which the variable oscillates), amplitude (the difference between the peak and the mean value of a wave), and acrophase (the time of peak activity) were calculated for each variable in each individual. Cosine curves are y t = M + A cos((2π/24)t + φ) + ϵ t , where y t is an observation at time t, M is the MESOR, A is the amplitude, and φ is the acrophase. ...
Six cows managed under extensive grazing conditions were used to study the effect of moving the animals to a higher grazing density on the circadian rhythms of temperature (T), heart rate (HR), and activity (ACT), which were recorded by implantable bio-loggers. Cows were maintained at a density of 1.5 livestock units per hectare (LSUs/ha) (low density, LD) until they were moved to a grazing area at 128 LSUs/ha (high density, HD). Animals were implanted subcutaneously with a T, HR, and ACT bio-logger, which was programmed to record data at 5-min intervals. For each animal, cosinor rhythmometry (the study of circadian rhythms by fitting a sine wave to a time series) was applied to the data recorded over five days in LD and HD. Mean MESOR (the average value around which the variable oscillates), amplitude (difference between the peak and the mean value of a wave), and acrophase (timing of peak activity) were calculated and evaluated statistically. Differences between mean day and nighttime values, and mean LD and HD values were calculated. Cows presented cosinor curves that fit a 24-h rhythm (P<0.001) in T, HR, and ACT at both densities. MESOR (T: 37.98 vs. 38.02°C; HR: 69.12 vs. 65.91 bpm; ACT: 49.39 vs. 40.41 mg, for LD and HD, respectively) and amplitude (T: 0.28 vs. 0.28°C; HR: 4.12 vs. 3.14 bpm; ACT: 18.14 vs. 11.28 mg, respectively) did not differ significantly between the two densities; however, significant (P<0.05) differences between densities occurred in the acrophase of the three variables; specifically, the T acrophase was two hours later at HD (2245 h) than LD (2045 h), and HR (LD: 1951; HD: 1649 h) and ACT acrophases three and two hours earlier at HD than LD (LD: 1447; HD: 1249 h), resp. T and ACT differed significantly (P<0.01) between daytime (mean ±S.E.) (37.92±0.19°C, 40.39±4.74 mg) and nighttime (38.14±0.17°C, 29.93±5.66 mg). In conclusion, our study suggests that a high animal grazing density might exacerbate the social competence for valuable resources for animals, resulting in shifting the circadian rhythmicity of temperature, heart rate and activity of the cows, advancing or delaying their acrophases.
Keywords: Cattle, density, Bio-loggers, Circadian Rhythm, tem
... As there is no ideal analysis method for this kind of data, we used a set of standard methods in rhythm research (Leise, 2017) based on different mathematical approaches and assumptions. Rhythmicity of the eclosion profiles was analyzed by autocorrelation implemented in a MATLAB (MathWorks, Inc., Natick, MA, USA) toolbox developed by Levine, Dowse, and colleagues (Levine et al., 2002); by a Fourier-based Lomb-Scargle (LS) analysis using ActogramJ (Schmid et al., 2011); and by cosinor model fitting to a 24-h period and subsequent zero-amplitude test using the web-based application "Cosinor.Online" (Molcan, 2019). For autocorrelation, rhythmicity was assessed by the rhythmicity index (RI, essentially the height of the third peak in the correlogram). ...
The adaptive significance of adjusting behavioral activities to the right time of the day seems obvious. Laboratory studies implicated an important role of circadian clocks in behavioral timing and rhythmicity. Yet, recent studies on clock-mutant animals questioned this importance under more naturalistic settings, as various clock mutants showed nearly normal diel activity rhythms under seminatural zeitgeber conditions. We here report evidence that proper timing of eclosion, a vital behavior of the fruit fly Drosophila melanogaster, requires a functional molecular clock under quasi-natural conditions. In contrast to wild-type flies, period ⁰¹ mutants with a defective molecular clock showed impaired rhythmicity and gating in a temperate environment even in the presence of a full complement of abiotic zeitgebers. Although period ⁰¹ mutants still eclosed during a certain time window during the day, this time window was much broader and loosely defined, and rhythmicity was lower or lost as classified by various statistical measures. Moreover, peak eclosion time became more susceptible to variable day-to-day changes of light. In contrast, flies with impaired peptidergic interclock signaling ( Pdf ⁰¹ and han ⁵³⁰⁴ PDF receptor mutants) eclosed mostly rhythmically with normal gate sizes, similar to wild-type controls. Our results suggest that the presence of natural zeitgebers is not sufficient, and a functional molecular clock is required to induce stable temporal eclosion patterns in flies under temperate conditions with considerable day-to-day variation in light intensity and temperature. Temperate zeitgebers are, however, sufficient to functionally rescue a loss of PDF-mediated clock-internal and -output signaling
... Based on the collected data, the analyses 142 were performed in Cosinor. online program(Molcan, 2019). ...
Background
The increasing amount of data points to the circadian timing system as an essential part of processes regulating androgen homeostasis. However, the relationship between stress response, timekeeping-, and steroidogenesis-related systems is unexplored.
Objective
The purpose of the study was to analyze the stress-response of the testosterone-producing Leydig cells depending on the stressful event’s time.
Materials and methods
The study was designed to follow the effects of 3-hour immobilization (IMO) applied at different periods during the day. The IMO performed once (1xIMO) or repeated in 10 consecutive days (10xIMO). Principal-component-analysis (PCA) followed the expression study of the clock and steroidogenic-related genes in Leydig cells.
Results
Both types of IMO in all investigated periods increased corticosterone and decreased testosterone blood level. Transcriptional analysis revealed different sensitivity to IMO events depending on the circadian time. The majority of steroidogenesis-related genes ( Lhcgr, Cyp11a1, Cyp17a1, Hsd3b1/2 ) were down-regulated in the inactive but unchanged or even up-regulated in the active phase of the day. Both types of IMO potentiated the expression of clock elements Bmal1 /BMAL1, Per1/ PER1 regardless of the day’s stage and reduced Reverba in the inactive phase. The PCA confirmed a major shift, for both IMO-types, in the transcription of steroidogenesis and clock genes across the inactive/active phase. Further, the diurnal pattern of the glucocorticoid receptor ( Nr3c1 /GR) expression in Leydig cells was increased in the inactive phase due to 10xIMO. The observed time-dependent IMO-response of the Leydig cells correlated with different GR engagements.
Discussion
Stress- and the circadian-system coordinatively shape Leydig cell’s physiology, assuming diverse GR engagement as a possible factor in mediating the diurnal effect of stress.
Conclusion
The Leydig cell’s stress-response depends on the time of the stressful situation, emphasizing the importance of circadian activity in supporting androgen homeostasis and male fertility.
... Time series data expected to follow circadian rhythms were analyzed by applying the least squares method to fit a sine wave i.e., Cosinor [72,73] by using the publicly available web-based application Cosinor. Online (cosinor.online/app/cosinor.php), as defined in [74]. ...
The feeding pattern and control of energy intake in mice housed in groups are poorly understood. Here, we determined and quantified the normal feeding microstructure of social male and female mice of the C57BL/6J genetic background fed a chow diet. Mice at 10w, 20w and 30w of age showed the expected increase in lean and fat mass, being the latter more pronounced and variable in males than in females. Under ad libitum conditions, 20w and 30w old females housed in groups showed significantly increased daily energy intake when adjusted to body weight relative to age-matched males. This was the combined result of small increases in energy intake during the nocturnal and diurnal photoperiods of the day without major changes in the circadian pattern of energy intake or spontaneous ambulatory activity. The analysis of the feeding microstructure suggests sex- and age-related contributions of meal size, meal frequency and intermeal interval to the control of energy intake under stable energy balance, but not under negative energy balance imposed by prolonged fasting. During the night, 10-20w old females ate less frequently bigger meals and spent more time eating them resulting in reduced net energy intake relative to age-matched males. In addition, male and female mice at all ages tested significantly shortened the intermeal interval during the first hours of re-feeding in response to fasting without affecting meal size. Further, 20-30w old males lengthened their intermeal interval as re-feeding time increased to reach fed-levels faster than age-matched females. Collectively, our results suggest that the physiological mechanisms controlling meal size (satiation) and the non-eating time spent between meals (satiety) during stable or negative energy balance are regulated in a sex- and age-dependent manner in social mice.
... The knockdown of Ptbp1 decreased the expression of PER1; however, it did not alter the oscillation phase of PER1 ( Figure 5B). The expression of PER1 as shown in Figure 5C was analyzed by the cosinor model and the presence and significance of oscillations was evaluated [40] (Supplementary Figure S3A-C). The reduced PTBP1 levels did not decrease the levels of endogenous Per1 mRNA ( Figure 2D) and the phenotype was also manifested in synchronized circadian rhythm analysis ( Figure 5C). ...
Circadian oscillations of mRNAs and proteins are the main features of circadian clock genes. Among them, Period1 (Per1) is a key component in negative-feedback regulation, which shows a robust diurnal oscillation and the importance of circadian rhythm and translational regulation of circadian clock genes has been recognized. In the present study, we investigated the 5'-untranslated region (5'-UTR) of the mouse core clock gene, Per1, at the posttranscriptional level, particularly its translational regulation. The 5'-UTR of Per1 was found to promote its translation via an internal ribosomal entry site (IRES). We found that polypyrimidine tract-binding protein 1 (PTBP1) binds to the 5'-UTR of Per1 and positively regulates the IRES-mediated translation of Per1 without affecting the levels of Per1 mRNA. The reduction of PTBP1 level also decreased the endogenous levels of the PER1 protein but not of its mRNA. As for the oscillation of PER1 expression, the disruption of PTBP1 levels lowered the PER1 expression but not the phase of the oscillation. PTBP1 also changed the amplitudes of the mRNAs of other circadian clock genes, such as Cryptochrome 1 (Cry1) and Per3. Our results suggest that the PTBP1 is important for rhythmic translation of Per1 and it fine-tunes the overall circadian system.
