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Time distributed data analysis by Cosinor.Online application

  • October 2019
DOI:10.1101/805960
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Lubos Molcan at Comenius University Bratislava
Lubos Molcan
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Abstract and Figures

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 familiar with MATLAB, R or other programming languages, users can adjust the parameters of the cosinor model setting based on their needs. Nowadays, many software applications are hosted on remote servers running 24/7. Server-based software applications enable quick analysis of big data sets and run on a wide range of terminal devices using standard web browsers. We created a simple web-based cosinor application, Cosinor.Online. The application code is written in PHP. TDD is handled using a MySQL database and can be copied directly from an Excel file to the webform. Analysis results contain information about setting the 24-h oscillation and a unique ID identifier. The identifier allows users to reopen data and results repeatedly over one month or remove their data from the MySQL database. Our web-based application can be used for a quick and simple inspection of 24-h oscillations of various biological and physiological TDD.
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Title
Time distributed data analysis by Cosinor.Online application
Running head
Cosinor.Online application
Author
Lubos Molcan
Affiliation
Department of Animal Physiology and Ethology, Faculty of Natural Sciences, Comenius
University, Bratislava, Slovakia
Correspondence
Department of Animal Physiology and Ethology, Faculty of Natural Sciences, Comenius
University in Bratislava, Ilkovicova 6, Bratislava, Slovakia, Phone: +421 260296 413, E-mail:
lubos.molcan@uniba.sk
Page 1 of 11
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The copyright holder for this preprint. http://dx.doi.org/10.1101/805960doi: bioRxiv preprint first posted online Oct. 18, 2019;
Abstract
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 familiar with MATLAB, R
or other programming languages, users can adjust the parameters of the cosinor model
setting based on their needs. Nowadays, many software applications are hosted on remote
servers running 24/7. Server-based software applications enable quick analysis of big data
sets and run on a wide range of terminal devices using standard web browsers. We created
a simple web-based cosinor application, Cosinor.Online. The application code is written in
PHP. TDD is handled using a MySQL database and can be copied directly from an Excel file
to the webform. Analysis results contain information about setting the 24-h oscillation and a
unique ID identifier. The identifier allows users to reopen data and results repeatedly over
one month or remove their data from the MySQL database. Our web-based application can
be used for a quick and simple inspection of 24-h oscillations of various biological and
physiological TDD.
Keywords
cosinor analysis, web application, PHP, MySQL, time distributed data
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1 Introduction
In living systems, processes vary over time because of the integration of biological and
environmental interactions. Among the most important and most studied are circadian
processes, which are oscillations that occur approximately 24-h. During regular light/dark
conditions, 24-h oscillations are very prominent in physiological systems. Physiological
changes [1], responses to stress [2], behavioural activities [3]⁠and pathophysiological events
are characterised by circadian changes [4]. Removal of the main circadian pacemaker, the
suprachiasmatic nucleus [5], or shifts in the regular light/dark environment [4] diminish
circadian amplitude [6], which can lead to loss of stress predictability [7] in the short term
manner. Over the long term, disturbing the circadian oscillations can change system-level set
points and may lead to pathological processes [8–10] including cancer development [11].
The presence and significance of 24-h oscillations in measured time distributed data
(TDD) can be done using cosinor analysis and the cosinor model. From a simple cosine
function, we can estimate mesor, amplitude, and acrophase. In general, physiological
functions can be better described by a complex series of harmonic functions [12].
The simple cosine function can be evaluated with a wide range of locally installed
native applications [13,14]. Skilled users can use the MATLAB or R programming languages,
which allow users to adjust the cosinor code, change the input form of the time series
(radians, degrees, hours or decimal) or adjust estimated period lengths and other parts of the
cosinor model [14,15].
With or without programming skills, evaluation of 24-h oscillations must be often done
on the same computer. On the other hand, at present, many software applications are hosted
on servers running 24/7. Besides that, server-based software applications enable quick
analysis of big data sets and run on a wide range of terminal devices using a standard web
browser only.
Therefore, we created a web-based cosinor application, Cosinor.Online. Application
code is written in PHP (hypertext preprocessor), a server-side scripting and general-purpose
programming language designed for web development. Input data are handled by MySQL
and can be copied directly from an Excel file to the webform.
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(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprint. http://dx.doi.org/10.1101/805960doi: bioRxiv preprint first posted online Oct. 18, 2019;
2 Mathematical modelling and code writing
We wrote our code in PHP in line with the MATLAB code [15], which implements a standard
cosinor method [14,16]. In the beginning, we solved a system of linear equations (Equation
1). Because of PHP implementation, we used matrix inversion instead of Gauss-Jordan
elimination. In extreme cases, if the matrix is badly conditioned, this approach can provide
false results.
From the Equation 1, where x
i= cos(ωt
i
)
,z
i= sin(ωt
i
)and nis a number of input
values, we obtained mesor (M
), Acosφ and Asinφ from which we calculated amplitude (A
)
(Equation 2). Using inverse tangent in radians and the signum function [15] we estimated
acrophase (φ
).
Mesor, amplitude and acrophase were entered into Equation 3 and we did cosine fit
to original TDD.
The significance of model fitting was done using the p-value as the F probability
density function [15].
Input and output cosinor data are handled and temporarily stored in the MySQL
database. Using a unique ID string, users can delete input and output data immediately after
the analysis is complete. If the user does not delete their data, all data is automatically
deleted one month from the beginning of the analysis. Any other data (e.g. operating system,
browser, country, etc.) are not stored in our database. Temporarily stored input and output
data are not used for any other analyses. Storing data in a MySQL database is only a
technical implementation to allow users to reload older analyses on different devices at
various times.
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(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.
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From the MySQL database, data are loaded using a randomly generated unique ID
string. Original input data are visualized as a scatter plot with a cosine fit as a line plot. Due
to online usage, cross-platform and cross-browser compatibility, we used Google Charts [17],
which are very easy to use for online visualization of a wide range of data.
3 Software usage
Software codes are hosted on the encrypted domain and the application is available at
https://cosinor.online address.
3.1 Input data
Cosinor.Online application consists of several pages. On the input page, users can enter
time and experimental values in decimal form, thus, 8:00 am is 8.00, 8:15 am is 8.25, 8:00
pm is 20.00, 8:15 pm is 20.25 and so forth (Figure 1).
Time and data columns must be the same size; if data is missing from a certain time
point, the relevant time-row must be removed.
Figure 1: Loading data is very easy: users can simply copy and paste columns from an
Excel file to the webform. Time and data columns must be the same size; if data is missing
from a certain time point, the relevant time-row must be removed.
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(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprint. http://dx.doi.org/10.1101/805960doi: bioRxiv preprint first posted online Oct. 18, 2019;
3.2 Output data
After the submission of the input TDD, users can see results and outputs from the model
describing 24-h oscillations in the loaded data. Original and calculated data are shown in a
table and visualized in the chart (Figure 2). Mesor is the average value around which the
variable oscillates. Amplitude is the difference between the peak (or trough) and the mean
value of a wave. Acrophase is the time of peak activity [12,13,16]. The application produces
mesor and amplitude in the units of user's input data; acrophase is provided in hours,
decimal form. Chart’s title, as well as vertical and horizontal axes, are adjustable and charts
are downloadable.
A
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The copyright holder for this preprint. http://dx.doi.org/10.1101/805960doi: bioRxiv preprint first posted online Oct. 18, 2019;
B
Figure 2: (A) On the output page users can find information about the date and time when
the analysis was done as well as the unique ID string. Mesor and amplitude are in the units
of the user's input data; acrophase is provided in hours, decimal form. (B) Original and
cosinor data are plotted on the chart.
3.3 Reload analysis
On the output page, users can find information about the date and time when the analysis
was done as well as the unique ID string, which can be inserted into the field on the Reload
analysis page. Using the unique ID string, users can repeatedly reopen their data and results
for up to one month. After this period, TDD and results are automatically removed from the
database without the possibility to recover them.
3.4 Remove data
Using the unique ID string, users can remove their data immediately and permanently from
the database; this function is available in the tab Remove data
.
3.5 Suggestions, questions
We believe, Cosinor.Online is very intuitive web-based application intended primarily for
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(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.
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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
.
4 Cosinor.Online versus other applications
A lot of different applications evaluate cosinor analysis, but a lot of them require installation
on a local drive, a specific type/version of the operating system, and/or the presence of
various add-ons. We were unable to install many of them on our hardware. Therefore we
compared Cosinor.Online application to scripts/packages, which run in software
environments, namely one script written for MATLAB [15] and two R packages, cosinor
(written by Michael Sachs; [18]) and cosinor2 (written by Augustin Mutak; [14]).
Mesor, amplitude, acrophase and the significance of the estimated model were the
same using different applications and Cosinor.Online (Table 1). Tested input data and results
from a comparison of Cosinor.Online versus other applications are freely available through
Google Sheets (https://bit.ly/CosinorOnlineExamples). R scripts and tested input data in text
files are downloadable at https://bit.ly/CosinorOnlineRData.
Table 1: 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).
Data
Set 1
Data
Set 2
Data
Set 3
Data
Set 4
Data
Set 5
Data
Set 6
Data
Set 7
Data
Set 8
Mesor
7.58
7.86
8.04
7.73
8.43
4.67
34.28
23.08
Amp
3.96
3.98
3.95
4.03
1.28
n.s.
7.92
6.82
Acr
11.37
or
23.37
11.62
or
23.61
11.84
or
23.84
12.44
or
24.44
9.75
or
21.75
n.s.
20.35
15.76
or
27.76
5 Discussion
Biological data vary in time and reveal significant 24-h oscillations [13]. This variability should
be considered and only data from similar time points between days should be compared.
Evaluation and comparison of TDD measured over the course of a day require cosinor
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analysis, which can detect significant 24-h variability.
Cosinor analysis can be done with locally installed native applications or using the
MATLAB [15] or R [14] programming languages. Anyway, evaluation of 24-h oscillations is
often limited to the same computer. We found online available applications, but there are
using outdated VBScript and ActiveX components that many modern web browsers do not
support. Thus, server-side software applications, in which software is hosted on servers
running 24/7, could be a solution. End users only need a personal computer, tablet or just a
phone with a standard web browser, so the user's low power devices can serve as terminals
to connect to a specific server with a specific request.
To take advantage of these changes, we created Cosinor.Online applications using
PHP and MySQL in line with the MATLAB code [15]. Input and output data are visualised
using Google Charts. Cosinor.Online application thus provides cross-platform and
cross-browser compatibility as well as the availability of data 24/7.
Some advanced and sophisticated chronomics online available analysis toolkits exist.
However, they do not allow to store data and are a bit complicated, mostly for beginners and
students. On the other hand, Cosinor.Online application is a very simple web-based
application. Loading TDD is easy: users can simply copy and paste columns from an Excel
file to the webform. Input and output data are processed in the background using PHP and
MySQL on the servers. Input and output data are stored on the servers. Users can adjust
titles in charts and download charts.
Individual analyses are given an original, randomly generated unique ID string, which
allows users to reopen or remove their data from the software's database. If users do not
remove their data, they are stored for up to one month. However, after this period, stored
data are automatically and permanently removed from the MySQL database.
Our purpose was to create a very simple and intuitive web-based application
especially for students, who have limited skills with data analysis or importing TDD into
different software applications but are skilled in using a wide range of modern and
permanently connected devices. We believe that our web-based application will also help
experienced researchers, particularly when they simply need to do a quick inspection of their
data: just copy, run and check.
However, there are some limitations to our application. Its current version fits only
24-h periods. Because of PHP implementation, Cosinor.Online application can provide false
results in very extreme cases. Our web-based application does not provide confidence
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(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.
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intervals of mesor and amplitude.
Cosinor.Online application is available 24/7 at https://cosinor.online address. The
developers are open to any suggestions for how to improve the Cosinor.Online application on
the basis of user feedback.
6 Conclusion
We created the web-based server-side application Cosinor.Online using PHP, MySQL and
Google Charts. Cosinor.Online application can be used for a quick and simple inspection of
the 24-h oscillations of various biological and physiological time distributed data. Users are
able to reopen the analysis on a wide range of devices for free up to one month.
7 Competing interest
None declared.⁠
8 Acknowledgement
We would like to thank Dr Richard Kollár and Dr Katarína Boďová for their mathematical
advice.
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... 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]. ...
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Full-text available
  • Mar 2023
Eight artificially reared lambs were used to study locomotory and feeding activities in the first three weeks of life by actigraphy. Lambs were fitted with a Bluetooth-enabled (BT) accelerometer and data were downloaded as activity counts at 1-min intervals (Vector Magnitude, VM). Sensors were programmed to act as beacons, and two sensors programmed as receivers were installed next to the rubber nipples of the milk feeder and recorded the serial numbers and labels of other nearby beacons through the BT signals. Mean (±SE) VM was 140 ± 3 counts/min, and time of day and week had significant (P < 0.001) effects. Overall activity did not differ significantly between sexes (males: 139 ± 5; females: 142 ± 5). The proportion of lambs that exhibited a 24-h circadian rhythm decreased with age (week 1 = 75%, week 2 = 63%, week 3 = 50%). Mean number of suckling sessions/day was 3.7 ± 0.2, the mean number of minutes suckling/day was 12.5 ± 0.9, and mean number of minutes/meal was 3.5 ± 0.2. Males dedicated more time/meal than females (males: 4.1 ± 0.4; females: 3.0 ± 0.2 min; P < 0.05). In conclusion, actigraphy is a useful tool for investigating the locomotor and feeding behaviour of artificially reared lambs, which detected a reduction in the circadian rhythmicity and the number of suckling sessions with age.
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Effects of packing on the diurnal rhythms of respiratory and heart rates in donkeys during the hot-dry season
Article
Full-text available
  • Dec 2022
This study aimed to evaluate the effects of packing (load carrying) on the diurnal rhythms of respiratory and heart rates in donkeys during the hot-dry season. Twenty 2- to 3-years-old donkeys weighing 93 ± 2.7 kg were divided into two groups to serve as subjects: Group 1 was subjected to packing + trekking, while group 2 was subjected to trekking only. All donkeys trekked 20 km on each experimental day. The procedure was repeated three times at one-day intervals. Thermal environmental parameters were recorded. Respiratory rate (RR) and heart rate (HR) were measured before and immediately (15 min) after the packing and/or trekking period. Continuous recordings of parameters were performed for 27 hr at 3-hr intervals beginning 16 hr after the last packing and/or trekking period. The RR rose significantly (P<0.05) immediately after packing + trekking and trekking only, from 30.15 ± 0.5 and 27.52 ± 0.5 cycles/min before packing + trekking and trekking only, respectively, to 43.78 ± 3.0 and 46.30 ± 1.8 cycles/min after them, respectively. The HR (76.63 ± 4.5 beats/min) in the packing + trekking donkeys was higher (P<0.05) than that of the trekking-only donkeys (62.33 ± 2.7 beats/min). The acrophase and bathyphase of the HR in both groups were recorded during the photophase and scotophase, respectively, with higher values (P<0.05) in the packing + trekking donkeys than in the trekking-only donkeys. The circadian rhythms of RR and HR did not differ between the groups of donkeys. In conclusion, packing + trekking was more stressful to the donkeys, significantly increasing the HR of donkeys subjected to packing + trekking, compared with trekking only.
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Melatonin modulates rectal and body surface temperatures and their circadian rhythmicity in donkeys (Equus asinus) subjected to packing during the hot-dry season
Article
  • Dec 2022
The study aimed to evaluate the effects of melatonin administration on rectal and body surface temperature (RT and BST, respectively) responses and their circadian rhythmicity in donkeys subjected to packing (load carrying) during the hot-dry season. Twenty donkeys were divided into two equal groups randomly: Groups 1 (packing + melatonin) and 2 (packing – melatonin), subjected to packing and both covered 20 km. The RT, BST, and thermal environmental parameters were measured before and after packing. The procedure was carried out three times within the week, one day apart. This was followed 16-h after the last (third) packing procedure by 27-h recording period of all the parameters at 3-h intervals. The RT (37.77 ± 0.1℃) recorded in packing + melatonin donkeys was lower (P < 0.05) than in (packing – melatonin) (38.29 ± 0.1℃) post-packing, while the BSTs in packing + melatonin donkeys were lower than in (packing – melatonin) donkeys, especially the neck (33.07 ± 0.6℃ vs 35.4 ± 0.7℃, respectively) and coronary band (30.58 ± 0.5℃ vs 33.38 ± 0.7℃, respectively) temperatures. In both groups 16-h post-packing, overall mean RT and BST values were not different, except the coronary band temperature (26.61 ± 0.8℃) that was lower (P < 0.05) in packing + melatonin donkeys than (packing – melatonin) donkeys (28.78 ± 1.4℃). Melatonin-exerted biphasic effects on circadian rhythms of RT and BSTs by reducing body temperatures during the photophase and increasing the values during the scotophase in pack donkeys. In conclusion, melatonin may enhance packing output in donkeys during the hot-dry season.
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Bio‑loggers inserted in intravaginal sponges, or subcutaneously, as tools to measure body temperature
Article
Full-text available
  • Dec 2022
Abstract The body temperature of animals can be measured by thermistors, thermocouples, or radiotelemetry devices that are implanted surgically under the skin, although the suitability of subcutaneous temperature as an indicator of core temperature can be limited because of abnormal temperature readings, probably affected by ambient temperature and animal inactivity. This study compared the use of bio-loggers designed to monitor subcutaneous temperature (Tsub), with their use embedded in intravaginal sponges to measure vaginal temperature (Tvag). Three ewes were implanted with a subcutaneous temperature bio-logger that was configured to record Tsub every 30 min for a month. Ewes were given an intravaginal sponge for 12 days two days later. Inside the sponges were installed programmed bio-loggers that measured Tvag every 5 min. The ambient temperature (Tamb) and relative humidity were monitored using mini data-loggers. Mean Tsub was lower (P
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Brown-Norway chromosome 1 mitigates the upregulation of pro-inflammatory pathways in mTAL cells and subsequent age-related CKD in Dahl SS/JrHsdMcwi Rats
Article
Chronic kidney disease (CKD) has a strong genetic component; however, the underlying pathways are not well understood. Dahl SS/Jr rats spontaneously develop CKD with age and are used to investigate the genetic determinants of CKD. However, there are currently several genetically diverse Dahl SS rats maintained at various institutions, and the extent to which some exhibit age-related CKD is unclear. We assessed glomerulosclerosis (GS) and tubulointerstitial fibrosis (TIF) in 3- and 6-month-old male and female SS/JrHsdMcwi, BN/NHsd/Mcwi (Brown-Norway (BN)), and consomic SS-Chr 1BN/Mcwi (SS.BN1) rats, in which chromosome 1 from the BN rat was introgressed into the genome of the SS/JrHsdMcwi rat. Rats were fed a 0.4% NaCl diet. GS (31±3 vs. 7±1%) and TIF (2.3±0.2 vs. 0.5±0.1) were significantly greater in 6- vs. 3-month-old SS/JrHsdMcwi rats, and CKD was exacerbated in males. GS was minimal in 6- and 3-month-old BN (3.9±0.6 vs. 1.2±0.4%) and SS.BN1 (2.4±0.5 vs. 1.0±0.3%) rats, and neither exhibited TIF. In SS/JrHsdMcwi and SS.BN1 rats, mean arterial blood pressure (BP) was significantly greater in 6- vs. 3-month-old SS/JrHsdMcwi (162±4 vs. 131±2 mmHg) but not SS.BN1 (115±2 vs. 116±1 mmHg) rats. In 6-month-old SS/JrHsdMcwi rats, BP was significantly greater in females. RNAseq analysis revealed that inflammatory pathways were upregulated in isolated medullary thick ascending (mTAL) tubules in 7-week-old SS/JrHsdMcwi rats, prior to the development of tubule pathology, vs. SS.BN1 rats. In summary, SS/JrHsdMcwi rats exhibit robust age-related progression of mTAL abnormalities, CKD, and hypertension, and gene(s) on chromosome 1 have a major pathogenic role in such changes.
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The circadian transcription factor ARNTL2 is regulated by weight-loss interventions in human white adipose tissue and inhibits adipogenesis
Article
Full-text available
  • Nov 2022
Misalignment of physiological circadian rhythms promotes obesity which is characterized by white adipose tissue (WAT) expansion. Differentiation of Adipose stem/progenitor cells (ASCs) contributes to WAT increase but the importance of the cellular clock in this process is incompletely understood. In the present study, we reveal the role of the circadian transcription factor Aryl hydrocarbon receptor nuclear translocator-like 2 (ARNTL2) in human ASCs, isolated from subcutaneous (s)WAT samples of patients undergoing routine elective plastic abdominal surgery. We show that circadian synchronization by serum-shock or stimulation with adipogenic stimuli leads to a different expression pattern of ARNTL2 relative to its well-studied paralogue ARNTL1. We demonstrate that ARNTL2 mRNA is downregulated in ASCs upon weight-loss (WL) whereas ARNTL2 protein is rapidly induced in the course of adipogenic differentiation and highly abundant in adipocytes. ARNTL2 protein is maintained in ASCs cooperatively by mechanistic Target of Rapamycin (mTOR) and Mitogen-activated Protein Kinase (MAPK) signalling pathways while ARNTL2 functions as an inhibitor on both circuits, leading to a feedback mechanism. Consistently, ectopic overexpression of ARNTL2 repressed adipogenesis by facilitating the degradation of ARNTL1, inhibition of Kruppel-Like Factor 15 (KLF15) gene expression and down-regulation of the MAPK-CCAAT/enhancer-binding protein β (C/EBPβ) axis. Western blot analysis of sWAT samples from normal-weight, obese and WL donors revealed that ARNTL2 protein was solely elevated by WL compared to ARNTL1 which underscores unique functions of both transcription factors. In conclusion, our study reveals ARNTL2 to be a WL-regulated inhibitor of adipogenesis which might provide opportunities to develop strategies to ameliorate obesity.
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cosinor2: Extended Tools for Cosinor Analysis of Rhythms
Research
Full-text available
  • Oct 2018
Statistical procedures for calculating population–mean cosinor, non–stationary cosinor, estimation of best–fitting period, tests of population rhythm differences and more.
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Repeated Phase Shifts in the Lighting Regimen Change the Blood Pressure Response to Norepinephrine Stimulation in Rats
Article
Full-text available
Disturbed circadian activity of the sympathetic system may be involved in negative consequences of chronodisruption on the cardiovascular system. We studied daily changes in pressure response to adrenergic stimulation in rats exposed to repeated phase advance shifts (PAS) of light/dark (LD) regimen. Blood pressure (BP), heart rate (HR) and locomotor activity was measured by radiotelemetry in normotensive Wistar rats exposed to repeated PAS (three 8-h shifts per week) lasting for 12 weeks. Norepinephrine was administered subcutaneously in the middle of L and D during week 12 of PAS exposure. In the control LD cycle, cardiovascular parameters exhibited significant daily rhythms with expected higher values during D than L phase. Rats exposed to PAS showed disturbed rhythms without a BP and HR increase. Administration of norepinephrine to control rats revealed daily variability in the cardiovascular response with higher stimulation of BP during L than D. This daily pattern of BP response to norepinephrine was diminished in the PAS group. The damped daily variability in pressure response to norepinephrine and augmented response during the light phase of the day suggest that the increased and desynchronised activity of the sympathetic system may worsen responses of the cardiovascular system to load in individuals exposed to irregular LD conditions.
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The long-term effects of phase advance shifts of photoperiod on cardiovascular parameters as measured by radiotelemetry in rats
Article
Full-text available
Cardiovascular parameters, such as blood pressure and heart rate, exhibit both circadian and ultradian rhythms which are important for the adequate functioning of the system. For a better understanding of possible negative effects of chronodisruption on the cardiovascular system we studied circadian and ultradian rhythms of blood pressure and heart rate in rats exposed to repeated 8 h phase advance shifts of photoperiod. The experiment lasted 12 weeks, with three shifts per week. Spectral power as a function of frequency for both circadian and harmonic ultradian rhythms was expressed as the circadian-ultradian power ratio. The circadian rhythms of blood pressure, heart rate and locomotor activity were recorded during the control light:dark (LD) regimen with higher values during the D in comparison with the L. Phase advance shifts resulted in a diminished circadian-ultradian power ratio for blood pressure, heart rate and locomotor activity indicating suppressed circadian control of these traits greater in heart rate than blood pressure. In conclusion, rats kept under irregular LD conditions have suppressed circadian control of heart rate, blood pressure and locomotor activity and rely more on an acute response to the LD regime. Their ability to anticipate regular loads can be weakened and in this way chronodisruption can contribute to the pathogenesis of cardiovascular diseases.
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Circadian control of the immune system
Article
Full-text available
  • Feb 2013
Circadian rhythms, which have long been known to play crucial roles in physiology, are emerging as important regulators of specific immune functions. Circadian oscillations of immune mediators coincide with the activity of the immune system, possibly allowing the host to anticipate and handle microbial threats more efficiently. These oscillations may also help to promote tissue recovery and the clearance of potentially harmful cellular elements from the circulation. This Review summarizes the current knowledge of circadian rhythms in the immune system and provides an outlook on potential future implications.
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Shifts in the light-dark cycle increase unpredictability of the cardiovascular system
Article
  • Jul 2017
Physiological variables such as heart rate (HR) and blood pressure (BP) exhibit long-term circadian rhythms, which can be disturbed by shift work. On the other hand, short-term oscillations in HR and BP have a high prognostic value. Therefore, we aimed to determine if the short-term variability, complexity and entropy of HR and BP would be affected by a regular light/dark (LD) cycle and phase delay shifts of the LD cycle, leading to chronodisruption. Telemetry-monitored rats were exposed first to the regular LD cycle and then to shifts in LD for 8 weeks. On the basis of long-term HR and BP recording and evaluation, we found circadian rhythms in HR and BP variability, complexity and entropy under regular LD cycles. Short-term exposure to shifts disturbed circadian rhythms of HR and BP variability, complexity and entropy, indicating chronodisruption. The power of circadian rhythms was suppressed after 8 weeks of phase delay shifts. Long-term exposure to shifts increased variability (p = 0.007), complexity (p < 0.001) and dark-time entropy (p = 0.006) of HR but not BP. This is the first study demonstrating long-term recording and estimation of HR and BP variability, complexity and entropy in conscious rats exposed to irregular lighting conditions. After long-term phase delay shifts, short-term variability of HR was less predictable than in controls. This study suggests that changes in short-term HR and BP oscillations induced by long-term shift work can negatively affect cardiovascular health.
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Endocrine and cardiovascular rhythms differentially adapt to chronic phase-delay shifts in rats
Article
  • Jul 2016
Disturbances in regular circadian oscillations can have negative effects on cardiovascular function, but epidemiological data are inconclusive and new data from animal experiments elucidating critical biological mechanisms are needed. To evaluate the consequences of chronic phase shifts of the light/dark (LD) cycle on hormonal and cardiovascular rhythms, two experiments were performed. In Experiment 1, male rats were exposed to either a regular 12:12 LD cycle (CONT) or rotating 8-h phase-delay shifts of LD every second day (SHIFT) for 10 weeks. During this period, blood pressure (BP) was monitored weekly, and daily rhythms of melatonin, corticosterone, leptin and testosterone were evaluated at the end of the experiment. In Experiment 2, female rats were exposed to the identical shifted LD schedule for 12 weeks, and daily rhythms of BP, heart rate (HR) and locomotor activity were recorded using telemetry. Preserved melatonin rhythms were found in the pineal gland, plasma, heart and kidney of SHIFT rats with damped amplitude in the plasma and heart, suggesting that the central oscillator can adapt to chronic phase-delay shifts. In contrast, daily rhythms of corticosterone, testosterone and leptin were eliminated in SHIFT rats. Exposure to phase shifts did not lead to increased body weight and elevated BP. However, a shifted LD schedule substantially decreased the amplitude and suppressed the circadian power of the daily rhythms of BP and HR, implying weakened circadian control of physiological and behavioural processes. The results demonstrate that endocrine and cardiovascular rhythms can differentially adapt to chronic phase-delay shifts, promoting internal desynchronization between central and peripheral oscillators, which in combination with other negative environmental stimuli may result in negative health effects.
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Time for Food: The Intimate Interplay between Nutrition, Metabolism, and the Circadian Clock
Article
  • Mar 2015
The circadian clock, a highly specialized, hierarchical network of biological pacemakers, directs and maintains proper rhythms in endocrine and metabolic pathways required for organism homeostasis. The clock adapts to environmental changes, specifically daily light-dark cycles, as well as rhythmic food intake. Nutritional challenges reprogram the clock, while time-specific food intake has been shown to have profound consequences on physiology. Importantly, a critical role in the clock-nutrition interplay appears to be played by the microbiota. The circadian clock appears to operate as a critical interface between nutrition and homeostasis, calling for more attention on the beneficial effects of chrono-nutrition. Copyright © 2015 Elsevier Inc. All rights reserved.
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