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Inferential statistical methods for estimating and comparing cosinor parameters.
Abstract
Biology, and medicine in particular, have traditionally relied on single samples. This article discusses cosinor methods leading to reference standards, chronodesms, that allow one to continue to deal with single values, provided these values are cost-effectively time-specified. The methods proposed are intended for sparse and short time-series containing a rhythm that satisfies the assumption of sinusoidality. (41 ref) (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Immune responses are widely accepted to be under circadian regulation via a molecular clock, with many practical consequences, but much less is known of how other biological rhythms could affect the immune system. In this study, we search for lunar rhythms (circalunar, circasemilunar, and circatidal cycles) in the immune expression of the recently marine-derived freshwater fish, the low-plate morph of the three-spined stickleback. We employed time series of immune expression (mRNA) measurements for 14 immune-associated genes, representing a variety of immunological pathways. Times series measurements were taken on fish populations in the wild, in seminatural outdoor mesocosms, and in the laboratory, according to sampling regimens originally designed to study circannual variation but with the additional potential to provide information about lunar variation. Our evidence best supported the existence of a very small endogenous tidal rhythm. This is consistent with previous suggestions of the existence of a primordial tidal endogenous clock, some elements of which may be conserved in animals evolving outside the marine environment.
Changes in lighting accompany modern urbanization trends and can lead to various pathologies based on circadian disturbances. In this study, we assessed the changes in the circadian rhythm of core body temperature (Tcore) and locomotor activity of Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) following exposure to different lighting conditions: extended light phase of the day (16 h–8 h, 20 h–4 h, 24 h–0 h), light pollution, monochromatic light, and bright light therapy. The telemetry data was collected after experimental lighting conditions during periods with standard lighting (12 h of light and 12 h of darkness) and was processed using linear and cosinor analysis. The daily rhythms of rats’ parameters persisted in accordance with the standard lighting regime. Tcore changes were observed in both groups compared to the initial period: in WKY, a decrease in Tcore during the darkness and an increase during the light; in SHR, the opposite trend, with Tcore increased during the darkness and decreased during the light phase of the day. A relationship between Tcore and activity was observed with weak correlation. WKY exhibited more pronounced signs of adaptive variation and desynchronization compared to SHR, which could be associated with a wider range of functional capabilities of the organism without cardiovascular pathology.
Background: Increasing evidence points at an important physiological role of the timekeeping system, known as the circadian clock (CC), regulating not only our sleep–awake rhythm but additionally many other cellular processes in peripheral tissues. It was shown in various cell types that environmental stressors, including ultraviolet B radiation (UV-B), modulate the expression of genes that regulate the CC (CCGs) and that these CCGs modulate susceptibility for UV-B-induced cellular damage. It was the aim of this pilot study to gain further insights into the CCs’ putative role for UV-B-induced photocarcinogenesis of skin cancer. Methods: Applying RT-PCR, we analyzed the expression of two core CCGs (brain and muscle ARNT-like 1 (Bmal1) and Period-2 (Per2)) over several time points (0–60 h) in HaCaT cells with and without 1,25-dihydroxyvitamin D (D3) and/or UV-B and conducted a cosinor analysis to evaluate the effects of those conditions on the circadian rhythm and an extended mixed-effects linear modeling to account for both fixed effects of experimental conditions and random inter-individual variability. Next, we investigated the expression of these two genes in keratinocytes representing different stages of skin photocarcinogenesis, comparing normal (Normal Human Epidermal Keratinocytes—NHEK; p53 wild type), precancerous (HaCaT keratinocytes; mutated p53 status), and malignant (Squamous Cell Carcinoma SCL-1; p53 null status) keratinocytes after 12 h under the same conditions. Results: We demonstrated that in HaCaT cells, Bmal1 showed a robust circadian rhythm, while the evidence for Per2 was limited. Overall expression of both genes, but especially for Bmal1, was increased following UV-B treatment, while Per2 showed a suppressed overall expression following D3. Both UVB and 1,25(OH)2D3 suggested a significant phase shift for Bmal1 (p < 0.05 for the acrophase), while no specific effect on the amplitude could be evidenced. Differential effects on the expression of BMAL1 and Per2 were found when we compared different treatment modalities (UV-B and/or D3) or cell types (NHEK, HaCaT, and SCL-1 cells). Conclusions: Comparing epidermal keratinocytes representing different stages of skin photocarcinogenesis, we provide further evidence for an independently operating timekeeping system in human skin, which is regulated by UV-B and disturbed during skin photocarcinogenesis. Our finding that this pattern of circadian rhythm was differentially altered by treatment with UV-B, as compared with treatment with D3, does not support the hypothesis that the expression of these CCGs may be regulated via UV-B-induced synthesis of vitamin D but might be introducing a novel photoprotective property of vitamin D through the circadian clock.
Artificial Light at Night (ALAN) is a fast-spreading threat to organisms, especially in coastal environments, where night lighting is increasing due to constant anthropization. Considering that ALAN affects a large diversity of coastal organisms, finding efficient solutions to limit these effects is of great importance but poorly investigated. The potential benefit of one strategy, in particular, should be studied since its use is growing: part-night lighting (PNL), which consists in switching off the lights for a few hours during nighttime. The aim of this study is to investigate the positive potential of the PNL strategy on the daily rhythm of the oyster Crassostrea gigas, a key species of coastal areas of ecological and commercial interest. Oysters were exposed to a control condition and three different ALAN modalities. A realistic PNL condition is applied, recreating a strategy of city policy in a coastal city boarding an urbanized bay (Lanton, Arcachon Bay, France). The PNL modality consists in switching off ALAN direct sources (5 lx) for 4 h (23−3 h) during which oysters are in darkness. Then, a PNL + skyglow (PNL + S) modality reproduces the previous one mimicking a skyglow (0.1 lx), an indirect ALAN source, during the direct lighting switch off, to get as close as possible to realistic conditions. Finally, the third ALAN condition mimics full-night direct lighting (FNL). Results revealed that PNL reduces some adverse effects of FNL on the behavioral daily rhythm. But, counterintuitively, PNL + S appears more harmful than FNL for some parameters of the behavioral daily rhythm. PNL + S modality is also the only one that affect oysters' clock and melatonin synthesis gene expression, suggesting physiological consequences. Thus, in realistic conditions, the PNL mitigation strategy might not be beneficial in the presence of skyglow, seeing worse for a coastal organism such as the oysters.
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Artificial Light At Night (ALAN) masks the natural light cycles and thus can disturb the synchronization of organisms' biological rhythms with their environment. Although coastlines are highly exposed to this growing threat, studies concerning the impacts of ALAN on coastal organisms remain scarce. In this study, we investigated the ALAN exposure effects at environmentally realistic intensities (0.1, 1, 10, 25 lx) on the oyster Crassostrea gigas, a sessile bivalve subject to light pollution on shores. We focused on the effects on oyster's daily rhythm at behavioral and molecular levels. Our results showed that ALAN disrupts the oyster's daily rhythm by increasing valve activity and annihilating day / night differences of expression of circadian clock and clock-associated genes. ALAN effects occur starting from 0.1 lx, in the range of artificial skyglow illuminances. We concluded that realistic ALAN exposure affects oysters' biological rhythm, which could lead to severe physiological and ecological consequences.
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Marine organisms living at high latitudes are faced with a light climate that undergoes drastic annual changes, especially during the polar night (PN) when the sun remains below the horizon for months. This raises the question of a possible synchronization and entrainment of biological rhythms under the governance of light at very low intensities. We analyzed the rhythms of the mussel Mytilus sp. during PN. We show that (1) mussels expressed a rhythmic behavior during PN; (2) a monthly moonlight rhythm was expressed; (3) a daily rhythm was expressed and influenced by both sunlight and moonlight; and (4) depending on the different times of PN and moon cycle characteristics, we were able to discriminate whether the moon or the sun synchronize the daily rhythm. Our findings fuel the idea that the capability of moonlight to synchronize daily rhythms when sunlight is not sufficient would be a crucial advantage during PN.
Data integration, data sharing and standardized analyses are important enablers for data-driven medical research. Circadian medicine is an emerging field with a particularly high need for coordinated and systematic collaboration between researchers from different disciplines. Datasets in circadian medicine are multimodal, ranging from molecular circadian profiles and clinical parameters to physiological measurements and data obtained from (wearable) sensors or reported by patients. Uniquely, data spanning both the time dimension as well as the spatial dimension (across tissues) are needed to obtain a holistic view of the circadian system. The study of human rhythms in the context of circadian medicine has to confront the heterogeneity of clock properties within and across subjects and our inability to repeatedly obtain relevant biosamples from one subject. This requires informatics solutions for integrating and visualizing relevant data types at various temporal resolutions ranging from milliseconds and seconds to minutes and several hours. Associated challenges range from a lack of standards that can be used to represent all required data in a common interoperable form, to challenges related to data storage, to the need to perform transformations for integrated visualizations, and to privacy issues. The downstream analysis of circadian rhythms requires specialized approaches for the identification, characterization, and discrimination of rhythms. We conclude that circadian medicine research provides an ideal environment for developing innovative methods to address challenges related to the collection, integration, visualization, and analysis of multimodal multidimensional biomedical data.
This investigation reviews how geomagnetic activity affects the circadian variation in blood pressure (BP) and heart rate (HR) and their variabilities of clinically healthy individuals. A small study in Alta, Norway (latitude of 70.0° N), serves to illustrate the methodology used to outline rules of procedure in exploring heliogeomagnetic effects on human physiology. Volunteers in the Alta study were monitored for at least 2 days between 18 March 2002 and 9 January 2005. Estimates of the circadian characteristics of BP and HR by cosinor and the Maximum Entropy Method (MEM) indicate an increase in the circadian amplitude of systolic (S) BP on geomagnetic-disturbance days compared to quiet days (p = 0.0236). Geomagnetic stimulation was found to be circadian-phase dependent, with stimulation in the evening inducing a 49.2% increase in the circadian amplitude of SBP (p = 0.0003), not observed in relation to stimulation in the morning. In two participants monitored for 7 days, the circadian amplitude of SBP decreased by 23.4% on an extremely disturbed day but increased by 50.3% on moderately disturbed days (p = 0.0044), suggesting a biphasic (hormetic) reaction of the circadian SBP rhythm to geomagnetics. These results indicate a possible role of geomagnetic fluctuations in modulating the circadian system.
Attention deficit hyperactivity disorder (ADHD) is a very common disorder in children and adults. A connection with sleep disorders, and above all, disorders of the circadian rhythm are the subject of research and debate. The circadian system can be represented on different levels. There have been a variety of studies examining 24-h rhythms at the behavioral and endocrine level. At the molecular level, these rhythms are based on a series of feedback loops of core clock genes and proteins. In this paper, we compared the circadian rhythms at the behavioral, endocrine, and molecular levels between children with ADHD and age- and BMI-matched controls, complementing the previous data in adults. In a minimally invasive setting, sleep was assessed via a questionnaire, actigraphy was used to determine the motor activity and light exposure, saliva samples were taken to assess the 24-h profiles of cortisol and melatonin, and buccal mucosa swaps were taken to assess the expression of the clock genes BMAL1 and PER2. We found significant group differences in sleep onset and sleep duration, cortisol secretion profiles, and in the expression of both clock genes. Our data suggest that the analysis of circadian molecular rhythms may provide a new approach for diagnosing ADHD in children and adults.
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