In the healthy state, both circadian rhythm and mood are stable against perturbations, yet they are capable of adjusting to altered internal cues or ongoing changes in external conditions. The dual demands of stability and flexibility are met by the collective properties of complex neural networks. Disruption of this balance underlies both circadian rhythm abnormality and mood disorders. However, we do not fully understand the network properties that govern the crosstalk between the circadian system and mood regulation. (...) This puzzle reflects a challenge at the center of neurobiology, and its solution requires the successful integration of existing data across all levels of neural organization, from molecules, cells, circuits, network dynamics, to integrated mental function. This essay discusses several open questions confronting the cross‐level synthesis, and proposes that circadian regulation, and its role in mood, stands as a uniquely tractable system to study the causal mechanisms of neural adaptation.Also watch the Video Abstract.Editor's suggested further reading in BioEssays Major depressive disorder: A loss of circadian synchrony? Abstract. (shrink)

In higher eukaryotes, circadian behaviour patterns have been dissected at the molecular level in Drosophila and, more recently, in the mouse. Considerable progress has been made in identifying some of the molecular components of the clock in the fly, where two genes, period (per) and timeless (tim), are essential for behavioural rhythmicity. The PER and TIM proteins show circadian cycles in abundance, and are part of a negative feedback loop with their own mRNAs. Within the pacemaker neurons, the (...) PER and TIM products are believed to form a complex which allows them to translocate to the nucleus, but how they repress their own transcription is unclear. TIM is rapidly degraded by light, a feature which permits a compelling molecular description of both behavioural light entrainment and phase responses to light pulses. The regulation of per and tim is altered in different Drosophila tissues, however, and comparative analyses of the two genes outside the Diptera reveals further unusual patterns of tissue‐specific regulation. Evolution appears to have modified the way in which the two genes are utilised to generate circadian phenotypes. More recently, the cloning of mouse clock genes, including putative per homologues, opens up exciting possibilities for mammalian molecular chronobiology. (shrink)

In higher eukaryotes, circadian behaviour patterns have been dissected at the molecular level in Drosophila and, more recently, in the mouse. Considerable progress has been made in identifying some of the molecular components of the clock in the fly, where two genes, period (per) and timeless (tim), are essential for behavioural rhythmicity. The PER and TIM proteins show circadian cycles in abundance, and are part of a negative feedback loop with their own mRNAs. Within the pacemaker neurons, the (...) PER and TIM products are believed to form a complex which allows them to translocate to the nucleus, but how they repress their own transcription is unclear. TIM is rapidly degraded by light, a feature which permits a compelling molecular description of both behavioural light entrainment and phase responses to light pulses. The regulation of per and tim is altered in different Drosophila tissues, however, and comparative analyses of the two genes outside the Diptera reveals further unusual patterns of tissue‐specific regulation. Evolution appears to have modified the way in which the two genes are utilised to generate circadian phenotypes. More recently, the cloning of mouse clock genes, including putative per homologues, opens up exciting possibilities for mammalian molecular chronobiology. (shrink)

Autoimmune diseases such as rheumatoid arthritis and gastrointestinal disorders such as stomach ulcers are often treated with drugs. NSAIDs, a common treatment in rheumatoid arthritis, may cause stomach ulcers which call for additional medications, notably antacids in the sense of drugs that suppress acid secretion by the stomach. Infection with Helicobacter pylori also plays a role in the ulcers. The infection is typically treated with antibiotics added to antacids. Considering NSAIDs and antacids, we suspect that overmedication is common to the (...) extent that particular diets are a better option. Current research and current treatments with these drugs are also problematic since circadian rhythms are mostly disregarded. All the processes involved in the disorders treated show marked variations in the course of the day. Hence experiments conforming to the guidelines of evidence-based medicine, and treatments in line with them, have outcomes strongly depending on the time factor. This calls for reforms in medicine with fresh inputs from biology. (shrink)

Autoimmune diseases such as rheumatoid arthritis and gastrointestinal disorders such as stomach ulcers are often treated with drugs. NSAIDs, a common treatment in rheumatoid arthritis, may cause stomach ulcers which call for additional medications, notably antacids in the sense of drugs that suppress acid secretion by the stomach. Infection with Helicobacter pylori also plays a role in the ulcers. The infection is typically treated with antibiotics added to antacids. Considering NSAIDs and antacids, we suspect that overmedication is common to the (...) extent that particular diets are a better option. Current research and current treatments with these drugs are also problematic since circadian rhythms are mostly disregarded. All the processes involved in the disorders treated show marked variations in the course of the day. Hence experiments conforming to the guidelines of evidence-based medicine, and treatments in line with them, have outcomes strongly depending on the time factor. This calls for reforms in medicine with fresh inputs from biology. (shrink)

The glowing light of cinema, which continues to claim supremacy as a collective site for evolving senses of time, has fundamentally changed since its inception, from exclusively projected light to primarily emitted light. Digital, rather than analog projectors, dominate in personal rather than public spheres. The physiological and behavioral effects of those technologies manipulate our biological clocks, creating an entanglement of time-sensing. Similarly, the art of cinema now relies far more upon energy-intensive materials and methods, from equipment to image manufacturing (...) and data flow. This essay takes the twelve-hour clock as a slanted optic to address those profound shifts, choosing a handful of moving-image artists to feature, including Deborah Stratman, Nikolaus Geyrhalter, and Mikael Kristersson, who are attempting to find alternative temporal modes of depicting the hyperobjectiveness of eternity, ecocrises, dystopias, and deep time on screen. (shrink)

It is not clear why cancer cells choose to disrupt their circadian clock rhythms, and whether such disruption governs a selective fitness and a survival advantage. In this review, I focus on understanding the impacts of clock gene disruption on a simpler model, such as the unicellular cyanobacterium, in order to explain how cancer cells may alter the circadian rhythm to reprogram their metabolism based on their needs and status. It appears to be that the activation of (...) the oxidative pentose phosphate pathway (OPPP) and production of NADPH, the preferred molecule for detoxification of reactive oxygen species, is a critical process for night survival in unicellular organisms. The circadian clock acts as a gatekeeper that controls how the organism will utilize its sugar, shifting sugar influx between glycolysis and OPPP. The circadian clock can thus act as a gatekeeper between an anabolic, proliferative mode and a homeostatic, survival mode. (shrink)

Two widely accepted assumptions within cognitive science are that (1) the goal is to understand the mechanisms responsible for cognitive performances and (2) computational modeling is a major tool for understanding these mechanisms. The particular approaches to computational modeling adopted in cognitive science, moreover, have significantly affected the way in which cognitive mechanisms are understood. Unable to employ some of the more common methods for conducting research on mechanisms, cognitive scientists’ guiding ideas about mechanism have developed in conjunction with their (...) styles of modeling. In particular, mental operations often are conceptualized as comparable to the processes employed in classical symbolic AI or neural network models. These models, in turn, have been interpreted by some as themselves intelligent systems since they employ the same type of operations as does the mind. For this paper, what is significant about these approaches to modeling is that they are constructed specifically to account for behavior and are evaluated by how well they do so—not by independent evidence that they describe actual operations in mental mechanisms. (shrink)

In many fields of biology, researchers explain a phenomenon by characterizing the responsible mechanism. This requires identifying the candidate mechanism, decomposing it into its parts and operations, recomposing it so as to understand how it is organized and its operations orchestrated to generate the phenomenon, and situating it in its environment. Mechanistic researchers have developed sophisticated tools for decomposing mechanisms but new approaches, including modeling, are increasingly being invoked to recompose mechanisms when they involve nonsequential organization of nonlinear operations. The (...) results often are dynamical mechanistic explanations. The steps in mechanistic research are illustrated using research on circadian rhythms. (shrink)

In the context of mechanistic explanation, reductionistic research pursues a decomposition of complex systems into their component parts and operations. Using research on the mechanisms responsible for circadian rhythms, I consider both the gains that have been made by discovering genes and proteins that figure in these intracellular oscillators and also highlight the increasingly recognized need to understand higher-level integration, both between cells in the central oscillator and between the central and peripheral oscillators. This history illustrates a common (...) need to complement reductionistic inquiry with investigations at higher-levels. Unlike most other accounts of reduction, the mechanistic framework accommodates this complementary relationship between reductionistic and systems approaches. (shrink)

In the middle of the twentieth century, physiologists interested in human biological rhythms undertook a series of field experiments in natural spaces that they believed could closely approximate conditions of biological timelessness. With the field of rhythms research was still largely on the fringes of the life sciences, natural spaces seemed to offer unique research opportunities beyond what was available to physiologists in laboratory spaces. In particular, subterranean caves and the High Arctic became archetypal ‘natural laboratories’ for the (...) study of human circadian (daily) rhythms. This paper is explores the field experiments which occurred in these ‘timeless spaces’. It considers how scientists understood these natural spaces as suitably ‘timeless’ for studying circadian rhythms and what their experimental practices can tell us about contemporary physiological notions of biological time, especially its relationship to ‘environmentality’ (Formosinho et al. in Stud History Philos Sci 91:148–158, 2022). In so doing, this paper adds to a growing literature on the interrelationship of field sites by demonstrating the ways that caves and the Arctic were connected by rhythms scientists. Finally, it will explore how the use of these particular spaces were not just scientific but also political – leveraging growing Cold War anxieties about nuclear fallout and the space race to bring greater prestige and funding to the study of circadian rhythms in its early years. (shrink)

Genetic analysis is revealing molecular components of circadian rhythms. The gene products of the period gene in Drosophila and the frequency gene in Neurospora oscillate with a circadian rhythm. A recent paper(1) has shown that the PERIOD protein can undergo both intermolecular and intramolecular interactions in vitro. The effects of temperature and two period mutations on these molecular interactions were compared to the effects of the mutations and temperature on the in vivo period length of circadian (...) rhythms. The results suggest that the molecular interactions may compete to maintain a rhythm with a constant period over a wide temperature range. (shrink)

Thanks to genetic and biochemical advances on the molecular mechanism of circadian rhythms in Drosophila, theoretical models closely related to experimental observations can be considered for the regulatory mechanism of the circadian clock in this organism. Modeling is based on the autoregulatory negative feedback exerted by a complex between PER and TIM proteins on the expression of per and tim genes. The model predicts the occurrence of sustained circadian oscillations in continuous darkness. When incorporating light‐induced TIM (...) degradation, the model accounts for damping of oscillations in constant light, entrainment of the rhythm by light‐dark cycles of varying period or photoperiod, and phase shifting by light pulses. The model further provides a molecular dynamical explanation for the permanent or transient suppression of circadian rhythmicity triggered in a variety of organisms by a critical pulse of light. Finally, the model shows that to produce a robust rhythm the various clock genes must be expressed at the appropriate levels since sustained oscillations only occur in a precise range of parameter values. BioEssays 22:84–93, 2000. ©2000 John Wiley & Sons, Inc. (shrink)

A wide range of biological processes, in all eukaryotes and in some prokaryotes, are controlled by rhythms with a period close to 24 hours. The circadian oscillator, which is responsible for generating these rhythms, is controlled by light signals that maintain its synchrony with the environmental day/night cycle. Higher plants exhibit many circadian rhythms, including rhythms in the transcription of specific genes. Molecular tools derived from such clock‐controlled genes have led to the identification of (...) several circadian rhythm mutants in the genetic model, Arabidopsis thaliana. The extensive understanding of photoperception in this species will make it a powerful system with which to investigate the light regulation of circadian rhythms. We compare Arabidopsis rhythms to the results from other systems, and discuss these data with respect to the current phototransduction models. (shrink)

The plant maintains a 24‐h circadian cycle that controls the sequential activation of many physiological and developmental functions. There is empirical evidence suggesting that two types of circadian rhythms exist. Some plant rhythms appear to be set by the light transition at dawn, and are calibrated to circadian (zeitgeber) time, which is measured from sunrise. Other rhythms are set by both dawn and dusk, and are calibrated to solar time that is measured from mid‐day. (...) Rhythms on circadian timing shift seasonally in tandem with the timing of dawn that occurs earlier in summer and later in winter. On the other hand, rhythms set to solar time are maintained independently of the season, the timing of noon being constant year‐round. Various rhythms that run in‐phase and out‐of‐phase with one another seasonally may provide a means to time and induce seasonal events such as flowering. (shrink)

The circadian clock is a cell autonomous oscillator that controls many aspects of physiology through generating rhythmic gene expression in a time of day dependent manner. In addition, in endothermic mammals body temperature cycles contribute to rhythmic gene expression. These body temperature‐controlled rhythms are hard to distinguish from classic circadian rhythms if analyzed in vivo in endothermic organisms. However, they do not fulfill all criteria of being circadian if analyzed in cell culture or in conditions (...) where body temperature of an endothermic organism can be manipulated. Here we review and compare these characteristics, discuss the core clock independent mechanism of temperature‐controlled alternative splicing and highlight the requirement of double‐checking rhythms that appear circadian within an endothermic organism in a system that allows temperature manipulation. (shrink)

BackgroundPrevious studies suggested a circadian variation of migraine attack onset, although, with contradictory results – possibly because of the existence of migraine subgroups with different circadian attack onset peaks. Migraine is primarily a brain disorder, and if the diversity in daily distribution of migraine attack onset reflects an important aspect of migraine, it may also associate with interictal brain activity. Our goal was to assess brain activity differences in episodic migraine subgroups who were classified according to their typical (...) circadian peak of attack onset.MethodsTwo fMRI studies were conducted with migraine without aura patients (n= 31 in Study 1,n= 48 in Study 2). Among them, three subgroups emerged with typical Morning, Evening, and Varying start of attack onset. Whole brain activity was compared between the groups in an implicit emotional processing fMRI task, comparing fearful, sad, and happy facial stimuli to neutral ones.ResultsIn both studies, significantly increased neural activation was detected to fearful (but not sad or happy) faces. In Study 1, the Evening start group showed increased activation compared to the Morning start group in regions involved in emotional, self-referential (left posterior cingulate gyrus, right precuneus), pain (including left middle cingulate, left postcentral, left supramarginal gyri, right Rolandic operculum) and sensory (including bilateral superior temporal gyrus, right Heschl’s gyrus) processing. While in Study 2, the Morning start group showed increased activation compared to the Varying start group at a nominally significant level in regions with pain (right precentral gyrus, right supplementary motor area) and sensory processing (bilateral paracentral lobule) functions.ConclusionOur fMRI studies suggest that different circadian attack onset peaks are associated with interictal brain activity differences indicating heterogeneity within migraine patients and alterations in sensitivity to threatening fearful stimuli. Circadian variation of migraine attack onset may be an important characteristic to address in future studies and migraine prophylaxis. (shrink)

A paradigm shift in the human chronotoxicity of xenobiotics would study two‐sided desynchronized phenomena of interfacial interactions between cyclic or periodic environmental insults and the endogenous response and recovery profile. These systems‐based networks are under the influence of well‐synchronized biological clocks and their metabolic regulators. This perspective argues in favor of addressing the concept of synchronization in studies involving critical life windows of susceptibility, or circadian rhythms, or 24‐hour (periodic) diurnal rhythms and answering whether these disruptions in (...) synchronization would affect response and recovery or disease phenotypes associated with environmental insults, e.g., xenobiotics. Synchronization or synchrony is defined as the totality of elements that appear during the same time period within a system, including the network of interactions between the system's elements. Desynchronized interfaces during critical life windows or in time‐repeated exposure events would likely lead to initiating a cascade of adverse health effects associated with differentiated disease phenotypes. (shrink)

On receiver-based teleosemantic theories of representation, the chemical states of the circadian clocks in animal, plant and cyanobacterial cells constitute signals of future states of affairs, often the rising and setting of the sun. This signalling is much more rigid than sophisticated representational systems like human language, but it is not simple on all dimensions. In most organisms the clock regulates many different circadian rhythms. The process of entrainment ensures that the mapping between chemical states of the (...) clock and the daily light-dark cycle is adjusted to deal with seasonal changes. In regulating anticipatory behaviour, the states of the clock look forward both to the time the behaviour is supposed to happen and the later time when the anticipated circumstances are supposed to arise. The case of the circadian clock shows that purely indicative signals can arise in very basic biological systems and brings into sharp relief the trade-offs involved in characterizing representational systems. On receiver-based teleosemantic theories, future-directed signals are not restricted to complex multicellular organisms but are ubiquitous in the biological world. (shrink)

Circadian rhythms in the sleep/wake cycle, along with a range of physiological measures, are severely disrupted in individuals with major depressive disorder (MDD). Moreover, several central circadian genes have been implicated as potential genetic factors underlying the illness through candidate gene studies and some genome wide association studies. However, investigations into the molecular underpinnings of circadian disturbances in the human brain have been quite challenging. In their recent publication, Li and colleagues have used a novel approach (...) to determine the rhythmic patterns of circadian gene expression in several regions of the human brain, and how these patterns are disrupted in MDD. Their findings demonstrate that in healthy subjects, several brain regions outside the suprachiasmatic nucleus (the master clock) exhibit diurnal gene expression patterns that are disrupted in the brains of MDD subjects. These findings will provide the foundation for future studies of gene‐specific drug targets, and biomarkers for the disease. (shrink)

ObjectiveIndividuals with an evening chronotype prefer to sleep later at night, wake up later in the day and perform best later in the day as compared to individuals with morning chronotype. Thus, college students without ADHD symptoms with evening chronotypes show reduced cognitive performance in the morning relative to nighttime. In combination with symptoms presented in attention deficit hyperactivity disorder, we predicted that having evening chronotype renders impairment in attention during the morning, when students require optimal performance, amplifying desynchrony.MethodFour hundred (...) college students were surveyed for evening chronotype and symptoms of ADHD. Of those surveyed, 43 students with evening chronotype performed laboratory attention tasks and were queried about fatigue during morning and evening sessions.ResultsStudents with ADHD symptoms demonstrated a greater decrement in sustained attentional vigilance when abstaining from stimulants and asked to perform cognitive tests at times misaligned with natural circadian rhythms in arousal compared to their non-ADHD counterparts with the same chronotype. While individuals with ADHD symptoms had slower reaction-times during sustained attention tasks in the morning session compared to those without symptoms, there was no significant group difference in working memory performance, even though both groups made more errors in the morning session compared to the evening session.ConclusionThese findings suggest that evening chronotype students with ADHD symptoms are at a greater disadvantage when having to perform sustained attention tasks at times that are not aligned to their circadian rhythm compared to their neuro-typical peers. The implications of this finding may be useful for the provision of disability accommodations to college age students with ADHD when they are expected to perform tasks requiring sustained attention at times misaligned with their circadian rhythms. (shrink)

Extending a normal 24 hours day by four hours is unexpectedly highly disruptive to daily rhythms in gene expression in the blood. Using a paradigm in which human subjects were exposed to a 28 hours day, Archer and colleagues show how this sleep‐altering forced desynchrony protocol caused complex disruption to daily rhythms in distinct groups of genes. Such perturbations in the temporal organisation of the blood transcriptome arise quickly, and point to the fragile nature of coordinated genomic activity. (...) Chronic disruption of the daily and circadian rhythms in sleep compromise health and well‐being and this study reveals potential new molecular targets to combat the disruptive effects of shift work and jetlag. (shrink)

Daylight is the primary cue used by circadian clocks to entrain to the day/night cycle so as to synchronize physiological processes with periodic environmental changes induced by Earth rotation.However, the temporal daylight pattern is not the same every day due to erratic weather fluctuations or regular seasonal changes. Then, how do circadian clocks operate properly in varying weather and seasons? In this paper, we discuss the strategy unveiled by recent studies of the circadian clock of Ostreococcus tauri, (...) the smallest free‐living eukaryotic organism. It combines mechanisms controlling light inputs and clock sensitivity, shaping both the dynamics of the core circadian oscillator and its forcing by light so as to ensure stable and precise synchronization in all weather and seasons.Editor's suggested further reading in BioEssays: Another place, another timer: Marine species and the rhythms of life Abstract. (shrink)

A circadian clock, with physiological characteristics similar to those of eukaryotes, functions in the photosynthetic prokaryote, cyanobacteria. The molecular mechanism of this clock has been efficiently dissected using a luciferase reporter gene that reports the status of the clock. A circadian clock gene cluster, kaiABC, has been cloned via rhythm mutants of cyanobacterium, Synechococcus, and many clock mutations mapped to the three kai genes. Although kai genes do not share any homology with clock genes so far identified in (...) eukaryotes, analysis of their expression suggests that a negative feedback control of kaiC expression by KaiC generates the circadian oscillation and that KaiA functions as a positive factor to sustain this oscillation. BioEssays 22:10–15, 2000. ©2000 John Wiley & Sons, Inc. (shrink)

Coordinated daily rhythms are evident in most aspects of our physiology, driven by internal timing systems known as circadian clocks. Our understanding of how biological clocks are built and function has grown exponentially over the past 20 years. With this has come an appreciation that disruption of the clock contributes to the pathophysiology of numerous diseases, from metabolic disease to neurological disorders to cancer. However, it remains to be determined whether it is the disruption of our rhythmic physiology (...) per se (loss of timing itself), or altered functioning of individual clock components that drive pathology. Here, we review the importance of circadian rhythms in terms of how we (and other organisms) relate to the external environment, but also in relation to how internal physiological processes are coordinated and synchronized. These issues are of increasing importance as many aspects of modern life put us in conflict with our internal clockwork. (shrink)

Daily rhythms are a ubiquitous feature of living systems. Generally, these rhythms are not just passive consequences of cyclic fluctuations in the environment, but instead originate within the organism. In mammals, including humans, the master pacemaker controlling 24‐hour rhythms is localized in the suprachiasmatic nuclei of the hypothalamus. This circadian clock is responsible for the temporal organization of a wide variety of functions, ranging from sleep and food intake, to physiological measures such as body temperature, heart (...) rate and hormone release. The retinal circadian clock was the first extra‐SCN circadian oscillator to be discovered in mammals and several studies have now demonstrated that many of the physiological, cellular and molecular rhythms that are present within the retina are under the control of a retinal circadian clock, or more likely a network of hierarchically organized circadian clocks that are present within this tissue. BioEssays 30:624–633, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Based on genetic and biochemical advances on the molecular mechanism of circadian rhythms, a computational model for the mammalian circadian clock is used to examine the dynamical bases of circadian‐clock‐related physiological disorders in humans. Entrainment by the light–dark cycle with a phase advance or a phase delay is associated with the Familial advanced sleep phase syndrome (FASPS) or the Delayed sleep phase syndrome (DSPS), respectively. Lack of entrainment corresponding to the occurrence of quasiperiodic oscillations with or (...) without phase jump can be associated with the non‐24 h sleep–wake syndrome. In the close vicinity of the entrainment domain, the model uncovers the possibility of infradian oscillations of very long period. Perturbation in the form of chronic jet lag, as used in mice, prevents entrainment of the circadian clock and results in chaotic or quasiperiodic oscillations. It is important to clarify the conditions for entrainment and for its failure because dysfunctions of the circadian clock may lead to physiological disorders, which pertain not only to the sleep–wake cycle but also to mood and cancer. BioEssays 30:590–600, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Circadian rhythm abnormalities in bipolar disorder have led to a search for genetic abnormalities in circadian "clock genes" associated with BD. However, no significant clock gene findings have emerged from genome-wide association studies. At least three factors could account for this discrepancy: complex traits are polygenic, the organization of the clock is more complex than previously recognized, and/or genetic risk for BD may be shared across multiple illnesses. To investigate these issues, we considered the clock gene network at (...) three levels: essential "core" clock genes, upstream circadian clock modulators, and downstream clock controlled genes. Using relaxed thresholds for GWAS statistical significance, we determined the rates of clock vs. control genetic associations with BD, and four additional illnesses that share clinical features and/or genetic risk with BD. Then we compared the results to a set of lithium-responsive genes. Associations with BD-spectrum illnesses and lithium-responsiveness were both enriched among core clock genes but not among upstream clock modulators. Associations with BD-spectrum illnesses and lithium-responsiveness were also enriched among pervasively rhythmic clock-controlled genes but not among genes that were less pervasively rhythmic or non-rhythmic. Our analysis reveals previously unrecognized associations between clock genes and BD-spectrum illnesses, partly reconciling previously discordant results from past GWAS and candidate gene studies. (shrink)

A vast network of cellular circadian clocks regulates 24‐hour rhythms of behavior and physiology in mammals. Complex environments are characterized by multiple, and often conflicting time signals demanding flexible mechanisms of adaptation of endogenous rhythms to external time. Traditionally this process of circadian entrainment has been conceptualized in a hierarchical scheme with a light‐reset master pacemaker residing in the hypothalamus that subsequently aligns subordinate peripheral clocks with each other and with external time. Here we review new (...) experiments using conditional mouse genetics suggesting that resetting of the circadian system occurs in a more “federated” and tissue‐specific fashion, which allows for increased noise resistance and plasticity of circadian timekeeping under natural conditions. (shrink)

This paper distinguishes between causal isolation robustness analysis and independent determination robustness analysis and suggests that the triangulation of the results of different epistemic means or activities serves different functions in them. Circadian clock research is presented as a case of causal isolation robustness analysis: in this field researchers made use of the notion of robustness to isolate the assumed mechanism behind the circadian rhythm. However, in contrast to the earlier philosophical case studies on causal isolation robustness analysis (...) (Weisberg and Reisman in Philos Sci 75:106–131, 2008 ; Kuorikoski et al. in Br J Philos Sci 61:541–567, 2010 ), robustness analysis in the circadian clock research did not remain in the level of mathematical modeling, but it combined it with experimentation on model organisms and a new type of model, a synthetic model. (shrink)

In mammals, a network of cellular circadian clocks organizes physiology and behavior along the 24‐h day cycle. The traditional hierarchical model of circadian clock organization with a central pacemaker and peripheral slave oscillators has recently been challenged by studies combining tissue‐specific mouse mutants with transcriptome analyses. First, a surprisingly small number of tissue rhythms are lost when only local clocks are ablated and, second, transcriptional circadian rhythms appear to be regulated by a complex mix of (...) local and systemic factors. As reviewed here, these findings suggest a more integrated model of clock network interaction with the central pacemaker as the main source of behavioral and systemic–physiological rhythms and peripheral clocks controlling some local rhythms while at the same time acting as gatekeepers that temporally adjust cellular responses to external stimuli. (shrink)

Circadian rhythms are responsible for 24‐hour oscillations in diverse biological processes. While the central genes governing circadian pacemaker rhythmicity have largely been identified, clock‐controlled output molecules responsible for regulating rhythmic behaviors remain largely unknown. Two recent reports from McDonald and Rosbash1 and Claridge‐Chang et al.2 address this issue. By identifying a large number of genes whose mRNA levels show circadian oscillations, the reports provide important new information on the biology of circadian rhythm. In addition, the (...) reports illustrate both the power and limitations of microarray‐based methods for profiling mRNA expression on a genomic scale. BioEssays 24:494–498, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

In many domains of biology, explanation takes the form of characterizing the mechanism responsible for a particular phenomenon in a specific biological system. How are such explanations generalized? One important strategy assumes conservation of mechanisms through evolutionary descent. But conservation is seldom complete. In the case discussed, the central mechanism for circadian rhythms in animals was first identified in Drosophila and then extended to mammals. Scientists' working assumption that the clock mechanisms would be conserved both yielded important generalizations (...) and served as a heuristic for discovery, especially when significant differences between the insect and mammalian mechanism were identified. †To contact the author, please write to: Department of Philosophy and Interdisciplinary Programs in Science Studies and Cognitive Science, 0119, University of California, San Diego, La Jolla, CA 92093‐0119; e‐mail: [email protected]. (shrink)

The pursuit of mechanistic explanations in biology has produced a great deal of knowledge about the parts, operations, and organization of mechanisms taken to be responsible for biological phenomena. Holist critics have often raised important criticisms of proposed mechanistic explanations, but until recently holists have not had alternative research strategies through which to advance explanations. This paper argues both that the results of mechanistic strategies has forced mechanists to confront ways in which whole systems affect their components and that new (...) representational and modeling strategies are providing tools for understanding these effects of whole systems upon components. Drawing from research on the mechanism responsible for circadian rhythms in mammals, I develop two examples in which mechanistic analysis is being integrated into a more holist perspective: research revealing intercellular integration of circadian mechanisms with those involved in cell metabolism and research revealing that stable␣rhythms are dependent on how individual cells in the suprachiasmatic nucleus synchronize with each other to generate regular rhythms. Tools such as network diagramming and computational modeling are providing means to integrate mechanistic models into accounts of whole systems. (shrink)

Graphical AbstractThe variable photoperiods of Northern latitudes challenge the entrainment capacity of the circadian pacemaker, which evolved under constant photoperiods in Equatorial regions. Entrainment to the erratic photoperiods facilitated by artificial light presents an additional challenge. Metabolic dysfunction and obesity are potential consequences of such desynchronization of circadian and environmental rhythms.

The power of the application of bioinformatics across multiple publicly available transcriptomic data sets was explored. Using 19 human and mouse circadian transcriptomic data sets, we found that NR1D1 and NR1D2 which encode heme‐responsive nuclear receptors are the most rhythmic transcripts across sleep conditions and tissues suggesting that they are at the core of circadian rhythm generation. Analyzes of human transcriptomic data show that a core set of transcripts related to processes including immune function, glucocorticoid signalling, and lipid (...) metabolism is rhythmically expressed independently of the sleep‐wake cycle. We also identify key transcripts associated with transcription and translation that are disrupted by sleep manipulations, and through network analysis identify putative mechanisms underlying the adverse health outcomes associated with sleep disruption, such as diabetes and cancer. Comparative bioinformatics applied to existing and future data sets will be a powerful tool for the identification of core circadian‐ and sleep‐dependent molecules. (shrink)

Most organisms display oscillations of approximately 24 hours in their physiology. In higher organisms, these circadian oscillations in biochemical and physiological processes ultimately control complex behavioral rhythms that allow an organism to thrive in its natural habitat. Daily and seasonal light cycles are mainly responsible for keeping the circadian system properly aligned with the environment. The molecular mechanisms responsible for the control of the circadian clock have been explored in a number of systems. Interestingly, the (...) class='Hi'>circadian oscillations that are responsive to environmental stimuli are present very early during development. This review focuses on the advantages of using the zebrafish to study the development of the vertebrate circadian system and light‐dependent signaling to the clock. BioEssays 24:419–426, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

Recent studies have highlighted the relevance of sleep for procrastination at work. Procrastination at work is defined as the irrational delay of the initiation or completion of work-related activities. In line with recent studies, we offer a self-regulation perspective on procrastination. We argue that procrastination is an outcome of depleted self-regulatory resources and that the restoration of self-regulatory resources during high-quality sleep at night would prevent procrastination.AimsIn an attempt to further develop this line of research, the current study aimed to (...) achieve a broader understanding of the relevance of sleep and circadian rhythm for procrastination. Therefore, we explored the effect of sleep quality on procrastination for different chronotypes. We also considered the shift to daylight saving time as a phenomenon that aggravates circadian misalignment and thereby later chronotypes' dependence on high-quality sleep. Specifically, we hypothesized that compared to employees with an earlier chronotype, employees with a later chronotype are more dependent on good sleep at night to prevent procrastination the next day. This effect would be especially pronounced after the shift to daylight saving time.MethodsFor this repeated-measures study, participants were 101 full-time employees. They completed a general questionnaire and day-specific questionnaires on the Monday before and the Monday following the shift to daylight saving time.ResultsThe multilevel analyses showed that employees procrastinated less on days following nights during which they slept better and that later chronotypes experienced more procrastination than earlier chronotypes. Our findings also supported the hypothesis that the relationship between sleep quality and procrastination is stronger for later chronotypes compared to earlier chronotypes on the Monday following the shift to daylight saving time. In other words, the lower the sleep quality of later chronotypes during the previous night, the more they procrastinated on the Monday following the shift to daylight saving time.DiscussionOur findings further corroborate the existing findings on the relevance of sleep and chronotype for well-being and performance at work. (shrink)

The marine ecosystem is governed by a multitude of environmental cycles, all of which are linked to the periodical recurrence of the sun or the moon. In accordance with these cycles, marine species exhibit a variety of biological rhythms, ranging from circadian and circatidal rhythms to circalunar and seasonal rhythms. However, our current molecular understanding of biological rhythms and clocks is largely restricted to solar‐controlled circadian and seasonal rhythms in land model species. Here, (...) we discuss the first molecular data emerging for circalunar and circatidal rhythms and present selected species suitable for further molecular analyses. We argue that a re‐focus on marine species will be crucial to understand the principles, interactions and evolution of rhythms that govern a broad range of eukaryotes, including ourselves. (shrink)