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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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... sinor.php) (Molcan, 2019). The variables derived from the cosine curve adjustment were the midline estimating statistic of rhythm (mesor), amplitude, and acrophase. ...
... Differences between the two groups were tested for significance by two-tailed t test. Cosinor analysis was performed on all biomarker data using the CosinorOnline application (https://cosinor.online/app/cosinor.php [27], accessed on 18 August 2023). Cosinor analysis is based upon fitting a cosinor curve to the data and assessing the curve that results in the least squared deviations of the measured data from the fitted curve [28]. ...
Asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) interfere with nitric oxide (NO) formation from L-arginine via different mechanisms. ADMA is a biomarker of cardiovascular disease and mortality, whilst SDMA is a biomarker of mortality after ischemic stroke. Homoarginine, another L-arginine-derived amino acid, is associated with stroke and congestive heart failure. Acute ischemic events like myocardial infarction show a time-of-day variation in the timing of their onset, as do NO-mediated vascular function and blood pressure. We studied whether the plasma concentrations of L-arginine-related amino acid metabolites show diurnal variation in a clinical study comparing 12 non-night shift workers with 60 rotating night shift workers. The plasma concentrations of L-arginine-related biomarkers, melatonin, and cortisol were measured every 3 h during a 24-h period. In addition, 24-h blood pressure recordings were performed. In non-night shift workers, L-arginine and homoarginine plasma concentrations showed diurnal variation with a 12-h period, which were both attenuated in night shift workers. ADMA and SDMA showed a 24-h rhythmicity with no significant differences in phase between night shift and non-night shift workers. The plasma profiles of melatonin and cortisol were not significantly different between both groups, suggesting that the rotating night shift work does not have a major influence on central suprachiasmatic nuclei clock timing. In addition, systolic and diastolic blood pressure patterns were similar between both groups. Our data show diurnal variation of dimethylarginines with the timing of their acrophases corresponding to the published timing of the peak incidence of cardiac ischemic events.
... in temperature, heart rate, and activity were graphed by fitting the time-series measurements of each ewe 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). The 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. ...
Context: the introduction of bio-sensors for monitoring real-time changes in physiological variables has helped to understand how external factors affect an animal’s resiliency to stressors. Aims: to quantify changes in temperature, heart rate, and locomotor activity in ewes during hormonal treatments for artificial insemination (AI) for up to 15 d after insemination. Method: Twelve ewes received a surgically implanted subcutaneous bio-logger to record data every 5 min. One week later, ewes received an intravaginal sponge for 12 d and AI was performed 54±1 h after sponge withdrawal. The data were divided into four periods: “Sponge in” (days -14 to -2), “Day before AI” (day -1)”, Day AI” (day 0), and “Post-AI” (days 1-5, days 6-10, and days 11-15). Key results: Ewes presented significantly (P<0.001) higher mean temperature and activity, and a lower heart rate when the sponges were in place than they in the days following AI. Mean body temperature in the “sponge in” period and the day before AI, but not in post-AI period, differed significantly (P<0.001) between pregnant and non-pregnant ewes. Non-pregnant ewes had a significantly (P<0.001) higher heart rate than did pregnant ewes when sponges were in and in the post-AI period. Non-pregnant ewes were significantly (P<0.001) less active than were pregnant ewes in the “sponge in” period and on days 1-5 after AI; however, the former were significantly (P<0.001) more active than were pregnant ewes on days 11-15 after AI. Conclusions: the subcutaneous bio-logger system documented 24-h variations in body temperature, heart rate, and locomotor activity before and after AI in ewes that had received an estrous-synchronizing hormonal treatment. Pregnancy status affected those variables and their circadian fluctuations at the time of the hormonal treatment and in the post-AI period. Implications: Any device designed for use in the study of PLF that allows a simple, non-invasive measurement of these variables might provide the basis for the development of a system that could identify females that are in an optimal state for insemination, and provide an early pregnancy prediction system.
... 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
