Period Of Rhythm Research Articles

Bayesian inference in ring attractor networks

Working memories are thought to be held in attractor networks in the brain. These attractors should keep track of the uncertainty associated with each memory, so as to weigh it properly against conflicting new evidence. However, conventional attractors do not represent uncertainty. Here, we show how uncertainty could be incorporated into an attractor, specifically a ring attractor that encodes head direction. First, we introduce a rigorous normative framework (the circular Kalman filter) for benchmarking the performance of a ring attractor under conditions of uncertainty. Next, we show that the recurrent connections within a conventional ring attractor can be retuned to match this benchmark. This allows the amplitude of network activity to grow in response to confirmatory evidence, while shrinking in response to poor-quality or strongly conflicting evidence. This "Bayesian ring attractor" performs near-optimal angular path integration and evidence accumulation. Indeed, we show that a Bayesian ring attractor is consistently more accurate than a conventional ring attractor. Moreover, near-optimal performance can be achieved without exact tuning of the network connections. Finally, we use large-scale connectome data to show that the network can achieve near-optimal performance even after we incorporate biological constraints. Our work demonstrates how attractors can implement a dynamic Bayesian inference algorithm in a biologically plausible manner, and it makes testable predictions with direct relevance to the head direction system as well as any neural system that tracks direction, orientation, or periodic rhythms.

On a method for detecting periods and repeating patterns in time series data with autocorrelation and function approximation

Detecting recurrent patterns in time series data is an important capability. The reason is that repeating patterns on the one hand indicate well defined processes that can be further analyzed once detected and on the other hand are a reliable feature to predict future occurrences and adapt accordingly. The challenge in real data to define a period is that a time series is usually also influenced by non-periodic dynamics and noise. In this work, a mathematical framework is proved to define regular patterns. Their properties are used within a suggested algorithm based on the concept of autocorrelation and function approximation to fit a model capturing the periodic part of the time series. Based on that model and a corresponding autocorrelation, a new score is defined to evaluate how well a hypothesized period fits to the time series. This score is particularly useful in a big data scenario where decisions for periodicity are needed to be taken automatically, which is one of the main achievement of the presented work. The period analysis algorithm is applied to data from two different use cases. The first one is a data center scenario where the information of the periodic pattern is used to create a feature that improves a machine learning framework predicting future resource demands. The feature represents the phase of the repeating pattern. In a second scenario, expression data from mice liver cells are investigated concerning periodic rhythms. A Python implementation of the presented algorithm is provided via a github repository under https://github.com/LauritzR/period-detection.

Homologs of Ancestral CNNM Proteins Affect Magnesium Homeostasis and Circadian Rhythmicity in a Model Eukaryotic Cell.

Biological rhythms are ubiquitous across organisms and coordinate key cellular processes. Oscillations of Mg2+ levels in cells are now well-established, and due to the critical roles of Mg2+ in cell metabolism, they are potentially fundamental for the circadian control of cellular activity. The identity of the transport proteins responsible for sustaining Mg2+ levels in eukaryotic cells remains hotly debated, and several are restricted to specific groups of higher eukaryotes. Here, using the eukaryotic minimal model cells of Ostreococcus tauri, we report two homologs of common descents of the Cyclin M (CNNM)/CorC protein family. Overexpression of these proteins leads to a reduction in the overall magnesium content of cells and a lengthening of the period of circadian gene expression rhythms. However, we observed a paradoxical increase in the magnesium content of the organelle fraction. The chemical inhibition of Mg2+ transport has a synergistic effect on circadian period lengthening upon the overexpression of one CNNM homolog, but not the other. Finally, both homologs rescue the deleterious effect of low extracellular magnesium on cell proliferation rates. Overall, we identified two CNNM proteins that directly affect Mg2+ homeostasis and cellular rhythms.

Trends and rhythms in carbonatites and kimberlites reflect thermo-tectonic evolution of Earth

Abstract Earth's thermo-tectonic evolution determines the way the planet's interior and surface interact and shows temporal changes in both trends and periodic rhythms. By sampling the subcontinental lithospheric mantle that represents the interface between the convecting mantle and the crust, carbonatite and kimberlite should be ideal rock types for documenting this evolution. The first-order secular rise of kimberlites over time has been noted by researchers, but there is much debate over how to interpret this trend, and their second-order variability has received less attention. We compiled a comprehensive global carbonatite database and compared it with an existing kimberlite one. We find that the numbers of carbonatites and kimberlites have similar increasing secular trends, with accelerated growth after ca. 1 Ga, and show the same periodic rhythms that have been synchronized to the supercontinent cycle since ca. 2.1 Ga. We link these trends and rhythms to the long-term change of Earth and the supercontinent cycle, both of which have altered the temperature of, and the subduction-recycled volatile flux into, the subcontinental lithosphere. Such consistent records in carbonatite and kimberlite behavior provide critical evidence for the synchronous thermo-tectonic evolution of the entire subcontinental lithosphere.

CRISPR/Cas9-mediated knockout of period reveals its function in the circadian rhythms of the diamondback moth Plutella xylostella.

Circadian clocks control the rhythmicity of many behaviors and physiological features of insects. To study the circadian clock of the moth Plutella xylostella, we employed CRISPR/Cas9-mediated genome editing to investigate the effect of loss of the clock gene period on the circadian rhythms. P. xylostella harbors a single copy of period. Phylogenetic analysis showed that P. xylostella PERIOD is more homologous to mouse PERIOD than the PERIOD proteins from bees, flies, mosquitos, and many other Lepidoptera, such as Danaus plexippus and Bombyx mori. The circadian rhythms in adult locomotor activity were altered in the period knockout strain of P. xylostella under light-dark (LD) and continuous dark (DD) conditions. Under the LD cycle, the wild-type moths displayed nocturnal activity with activity peaking very early after lights off and quickly declining after lights on. In contrast, the period knockout strain had no peak in activity when the lights were turned off and exhibited steady activity throughout the hours of darkness. Interestingly, under DD conditions, our results showed that the locomotor rhythm can be maintained without period gene, but at a lower rhythmicity ratio than wild-type. In addition, knockout of period in P. xylostella changed circadian rhythms patterns related to pupal eclosion, mating, egg-laying, and egg hatching. Mechanistically, loss of PERIOD disrupted the molecular rhythm of period and changed the clock transcription rhythm in the heads of the moths under LD and DD conditions. Together, our study indicates that the PERIOD is required for normal expression of many behavioral rhythms in P. xylostella.

Circadian expression and specific localization of synaptotagmin17 in the suprachiasmatic nucleus, the master circadian oscillator in mammals

The localization and function of synaptotagmin (syt)17 in the suprachiasmatic nucleus (SCN) of the brain, which is the master circadian oscillator, were investigated. The Syt17 mRNA-containing neurons were mainly situated in the shell region while SYT17 immunoreactive cell bodies and neural fibers were detected in the core and shell of the SCN and the subparaventricular zone (SPZ). Further, electron microscopy analysis revealed SYT17 in the rough endoplasmic reticulum (rER), Golgi apparatus (G), and large and small vesicles of neurons. Syt17 mRNA expression in the SCN showed a circadian rhythm, and light exposure at night suppressed its expression. In addition, the free running period of locomotor activity rhythm was shortened in Syt17-deletion mutant mice. These findings suggest that SYT17 is involved in the regulation of circadian rhythms.

A methylbenzimidazole derivative regulates mammalian circadian rhythms by targeting Cryptochrome proteins.

Background: Impairment of the circadian clock has been associated with numerous diseases, including sleep disorders and metabolic disease. Although small molecules that modulate clock function may form the basis of drug discovery of clock-related diseases, only a few compounds that selectively target core clock proteins have been identified. Three scaffolds were previously discovered as small-molecule activators of the clock protein Cryptochrome (CRY), and they have been providing powerful tools to understand and control the circadian clock system. Identifying new scaffolds will expand the possibilities of drug discovery. Methods: A methylbenzimidazole derivative TH401 identified from cell-based circadian screens was characterized. Effects of TH401 on circadian rhythms were evaluated in cellular assays. Functional assays and X-ray crystallography were used to elucidate the effects of the compound on CRY1 and CRY2 isoforms. Results: TH401 lengthened the period of circadian rhythms and stabilized both CRY1 and CRY2. The compound repressed Per2 reporter activity, which was reduced by Cry1 or Cry2 knockout and abolished by Cry1/Cry2 double knockout, indicating the dependence on CRY isoforms. Thermal shift assays showed slightly higher interaction of TH401 with CRY2 over CRY1. The crystal structure of CRY1 in complex with TH401 revealed a conformational change of the gatekeeper W399, which is involved in isoform-selectivity determination. Conclusions: The present study identified a new small molecule TH401 that targets both CRY isoforms. This compound has expanded the chemical diversity of CRY activators, and will ultimately aid in the development of therapeutics against circadian clock-related disorders.

NA-CPG: A robust and stable rhythm generator for robot motion control

Central pattern generators (CPGs) have been widely applied in robot motion control for the spontaneous output of coherent periodic rhythms. However, the underlying CPG network exhibits good convergence performance only within a certain range of parameter spaces, and the coupling of oscillators affects the network output accuracy in complex topological relationships. Moreover, CPGs may diverge when parameters change drastically, and the divergence is irreversible, which is catastrophic for the control of robot motion. Therefore, normalized asymmetric CPGs (NA-CPGs) that normalize the amplitude parameters of Hopf-based CPGs and add a constraint function and a frequency regulation mechanism are proposed. NA-CPGs can realize parameter decoupling, precise amplitude output, and stable and rapid convergence, as well as asymmetric output waveforms. Thus, it can effectively cope with large parameter changes to avoid network oscillations and divergence. To optimize the parameters of the NA-CPG model, a reinforcement-learning-based online optimization method is further proposed. Meanwhile, a biomimetic robotic fish is illustrated to realize the whole optimization process. Simulations demonstrated that the designed NA-CPGs exhibit stable, secure, and accurate network outputs, and the proposed optimization method effectively improves the swimming speed and reduces the lateral swing of the multijoint robotic fish by 6.7% and 41.7%, respectively. The proposed approach provides a significant improvement in CPG research and can be widely employed in the field of robot motion control.

A methylbenzimidazole derivative regulates mammalian circadian rhythms by targeting Cryptochrome proteins

Background: Impairment of the circadian clock has been associated with numerous diseases, including sleep disorders and metabolic disease. Although small-molecules that modulate clock function may form the basis of drug discovery of clock-related diseases, only a few compounds that selectively target core clock proteins have been identified. Three scaffolds were previously discovered as small-molecule activators of the clock protein Cryptochrome (CRY), and they have been providing powerful tools to understand and control the circadian clock system. Identifying new scaffolds will expand the possibilities of drug discovery. Methods: A methylbenzimidazole derivative TH401 identified from cell-based circadian screens was characterized. Effects of TH401 on circadian rhythms were evaluated in cellular assays. Functional assays and X-ray crystallography were used to elucidate the effects of the compound on CRY1 and CRY2 isoforms. Results: TH401 lengthened the period of circadian rhythms and stabilized both CRY1 and CRY2. The compound repressed Per2 reporter activity, which was reduced by Cry1 or Cry2 knockout and abolished by Cry1/Cry2 double knockout, indicating the dependence on CRY isoforms. Thermal shift assays showed slightly higher interaction of TH401 with CRY2 over CRY1. The crystal structure of CRY1 in complex with TH401 revealed a conformational change of the gatekeeper W399, which is involved in isoform-selectivity determination. Conclusions: The present study identified a new small-molecule TH401 that targets both CRY isoforms. This compound has expanded the chemical diversity of CRY activators, and will ultimately aid in the development of therapeutics against circadian clock-related disorders.

A methylbenzimidazole derivative regulates mammalian circadian rhythms by targeting Cryptochrome proteins.

Background: Impairment of the circadian clock has been associated with numerous diseases, including sleep disorders and metabolic disease. Although small-molecules that modulate clock function may form the basis of drug discovery of clock-related diseases, only a few compounds that selectively target core clock proteins have been identified. Three scaffolds were previously discovered as small-molecule activators of the clock protein Cryptochrome (CRY), and they have been providing powerful tools to understand and control the circadian clock system. Identifying new scaffolds will expand the possibilities of drug discovery. Methods: A methylbenzimidazole derivative TH401 identified from cell-based circadian screens was characterized. Effects of TH401 on circadian rhythms were evaluated in cellular assays. Functional assays and X-ray crystallography were used to elucidate the effects of the compound on CRY1 and CRY2 isoforms. Results: TH401 lengthened the period of circadian rhythms and stabilized both CRY1 and CRY2. The compound repressed Per2 reporter activity, which was reduced by Cry1 or Cry2 knockout and abolished by Cry1/Cry2 double knockout, indicating the dependence on CRY isoforms. Thermal shift assays showed slightly higher interaction of TH401 with CRY2 over CRY1. The crystal structure of CRY1 in complex with TH401 revealed a conformational change of the gatekeeper W399, which is involved in isoform-selectivity determination. Conclusions: The present study identified a new small-molecule TH401 that targets both CRY isoforms. This compound has expanded the chemical diversity of CRY activators, and will ultimately aid in the development of therapeutics against circadian clock-related disorders.

Chronobiology of epilepsy and sudden unexpected death in epilepsy

Epilepsy is a neurological disease characterized by spontaneous, unprovoked seizures. Various insults render the brain hyperexcitable and susceptible to seizure. Despite there being dozens of preventative anti-seizure medications available, these drugs fail to control seizures in nearly 1 in 3 patients with epilepsy. Over the last century, a large body of evidence has demonstrated that internal and external rhythms can modify seizure phenotypes. Physiologically relevant rhythms with shorter periodic rhythms, such as endogenous circadian rhythms and sleep-state, as well as rhythms with longer periodicity, including multidien rhythms and menses, influence the timing of seizures through poorly understood mechanisms. The purpose of this review is to discuss the findings from both human and animal studies that consider the effect of such biologically relevant rhythms on epilepsy and seizure-associated death. Patients with medically refractory epilepsy are at increased risk of sudden unexpected death in epilepsy (SUDEP). The role that some of these rhythms play in the nocturnal susceptibility to SUDEP will also be discussed. While the involvement of some of these rhythms in epilepsy has been known for over a century, applying the rhythmic nature of such phenomenon to epilepsy management, particularly in mitigating the risk of SUDEP, has been underutilized. As our understanding of the physiological influence on such rhythmic phenomenon improves, and as technology for chronic intracranial epileptiform monitoring becomes more widespread, smaller and less invasive, novel seizure-prediction technologies and time-dependent chronotherapeutic seizure management strategies can be realized.

Subepicardial ischemia vs cardiac memory after tachycardia by intranodal reentry. case report and literature review

Cardiac memory is an electrophysiological property that is expressed as persistent electrophysiological changes in response to variations in the rate and sequence of cardiac electric activation and is defined as the persistent changes of the T wave on the electrocardiogram after a period of rhythms of wide QRS widened, and that becomes evident once the normal ventricular activation pattern is restored.1 The first evidence of its existence arises from case reports where changes in the polarity of the T wave were observed after transient episodes of tachyarrhythmias. Subsequently, it was demonstrated how ventricular activation by external sources in a prolonged way induces persistent changes in the electrocardiogram, and those changes persist after eliminating this source.6,8 Electrical memory can occur in a short and long term, when it is short-term, the changes are due to the modulation of the electrical activity of individual cardiac cells or cell to cell interaction, while long-term memory involves the synthesis of proteins and / or structural changes.8

Spatiotemporal pattern of periodic rhythms in delayed Van der Pol oscillators for the CPG-based locomotion of snake-like robot

This is the further research on the delayed half-center oscillator (DHCO) neural system presented in our previous paper (Song and Xu in Nonlinear Dyn 108:2595–2609, 2022. https://doi.org/10.1007/s11071-022-07222-y). The DHCO is used to construct a CPG (central pattern generator) neural system to control locomotion of a snake-like robot with pitch-yaw connecting configuration. To this end, we firstly give an improved model of the VDP (Van der Pol) oscillator. Employing mutually coupled delay, a pair of VDP oscillator is connected to produce an half-center oscillator (HCO) module with time delay that is called as a DHCO (delayed HCO) model. Based on the analysis of the Hopf bifurcation, periodic rhythm and their spatiotemporal patterns of the DHCO are illustrated in the different regions of parameters. The DHCO presents periodic rhythms with synchronous and anti-synchronous patterns, which is to control joint actuators combined in snake-like robot with pitch-yaw connecting configuration. To realize a backward propulsive wave to promote snake-like robotic locomotion, based on the DHCOs, we construct a chain type of the CPG neural system combined with a new unidirectional delay in which phase difference can be regulated. Numerical simulations are illustrated that the CPG neural system can control snake-like robot to move with serpentine, rectilinear, and side-winding patterns in the forward and backward directions. The results show that the snake-like robot can be controlled in expected locomotion patterns for a region but not a fixed value of the controlling parameters. Further, the corresponding regions of the parameters are obtained by using theoretical dynamical analysis but not a trial-and-error method. The snake-like robot gets smooth and stable gait transition with parameter changing.

Effects of Food Availability Cycles on Phase and Period of Activity-rest Rhythm in Drosophila melanogaster.

Foraging and feeding are indispensable for survival and their timing depends not only on the metabolic state of the animal but also on the availability of food resources in their environment. Since both these aspects are subject to change over time, these behaviors exhibit rhythmicity in occurrence. As the locomotor activity of an organism is related to its disposition to acquire food, and peak feeding in fruit flies has been shown to occur at a particular time of the day, we asked if cyclic food availability can entrain their rhythmic activity. By subjecting flies to cyclic food availability, that is, feeding-starvation (FS) cycles, we provided food cues contrasting to the preferred activity times and observed if this imposed cycling in food availability could entrain the activity-rest rhythm. We found that phase control, which is a property integral to entrainment, was not achieved despite increasing starvation duration of FS cycles (FS 12:12, FS 10:14, and FS 8:16). We also found that flies subjected to T21 and T26 FS cycles were unable to match period of the activity rhythm to short or long T-cycles. Taken together, these results show that external food availability cycles do not entrain the activity-rest rhythm of fruit flies. However, we find that starvation-induced hyperactivity causes masking which results in phase changes. In addition, T-cycle experiments resulted in minor period changes during FS treatment. These findings highlight that food cyclicity by itself may not be a potent zeitgeber but may act in unison with other abiotic factors like light and temperature to help flies time their activity appropriately.

Cryptochrome 1 as a state variable of the circadian clockwork of the suprachiasmatic nucleus: Evidence from translational switching

The suprachiasmatic nucleus (SCN) of the hypothalamus is the principal clock driving circadian rhythms of physiology and behavior that adapt mammals to environmental cycles. Disruption of SCN-dependent rhythms compromises health, and so understanding SCN time keeping will inform management of diseases associated with modern lifestyles. SCN time keeping is a self-sustaining transcriptional/translational delayed feedback loop (TTFL), whereby negative regulators inhibit their own transcription. Formally, the SCN clock is viewed as a limit-cycle oscillator, the simplest being a trajectory of successive phases that progresses through two-dimensional space defined by two state variables mapped along their respective axes. The TTFL motif is readily compatible with limit-cycle models, and in Neurospora and Drosophila the negative regulators Frequency (FRQ) and Period (Per) have been identified as state variables of their respective TTFLs. The identity of state variables of the SCN oscillator is, however, less clear. Experimental identification of state variables requires reversible and temporally specific control over their abundance. Translational switching (ts) provides this, the expression of a protein of interest relying on the provision of a noncanonical amino acid. We show that the negative regulator Cryptochrome 1 (CRY1) fulfills criteria defining a state variable: ts-CRY1 dose-dependently and reversibly suppresses the baseline, amplitude, and period of SCN rhythms, and its acute withdrawal releases the TTFL to oscillate from a defined phase. Its effect also depends on its temporal pattern of expression, although constitutive ts-CRY1 sustained (albeit less stable) oscillations. We conclude that CRY1 has properties of a state variable, but may operate among several state variables within a multidimensional limit cycle.

Genome-Wide Identification and Analysis of the Aureochrome Gene Family in Saccharina japonica and a Comparative Analysis with Six Other Algae.

Aureochrome (AUREO) is a kind of blue light photoreceptor with both LOV and bZIP structural domains, identified only in Stramenopiles. It functions as a transcription factor that responds to blue light, playing diverse roles in the growth, development, and reproduction of Stramenopiles. Most of its functions are currently unknown, especially in the economically important alga S. japonica farmed on a large scale. This study provided a comprehensive analysis of the characteristics of AUREO gene families in seven algae, focusing on the AUREOs of S. japonica. AUREO genes were strictly identified from seven algal genomes. Then AUREO phylogenetic tree was constructed from 44 conserved AUREO genes collected. These AUREO genes were divided into five groups based on phylogenetic relationships. A total of 28 genes unnamed previously were named according to the phylogenetic tree. A large number of different cis-acting elements, especially bZIP transcription factors, were discovered upstream of AUREO genes in brown algae. Different intron/exon structural patterns were identified among all AUREOs. Transcriptomic data indicated that the expression of Sj AUREO varied significantly during the different development stages of S. japonica gametophytes. Periodic rhythms of light induction experiments indicate that Sj AUREO existed in a light-dependent circadian expression pattern, differing from other similar studies in the past. This may indicate that blue light affects gametophyte development through AUREO as a light signal receptor. This study systematically identified and analyzed the AUREO gene family in seven representative brown algae, which lay a good foundation for further study and understanding of AUERO functions in agal growth and development.

Nmu/Nms/Gpr176 Triple-Deficient Mice Show Enhanced Light-Resetting of Circadian Locomotor Activity.

The suprachiasmatic nucleus (SCN) is the master circadian clock in mammals and is properly entrained by environmental light cycle. However, the molecular mechanism(s) determining the magnitude of phase shift by light is still not fully understood. The orphan G-protein-coupled receptor Gpr176 is enriched in the SCN, controls the pace (period) of the circadian rhythm in behavior but is not apparently involved in the light entrainment; Gpr176-/- animals display a shortened circadian period in constant darkness but their phase-resetting responses to light are normal. Here, we performed microarray analysis and identified enhanced mRNA expression of neuromedin U (Nmu) and neuromedin S (Nms) in the SCN of Gpr176-/- mice. By generating C57BL/6J-backcrossed Nmu/Nms/Gpr176 triple knockout mice, we noted that the mutant mice had a greater magnitude of phase shift in response to early subjective night light than wildtype mice, while Nmu/Nms double knockout mice as well as Gpr176 knockout mice are normal in the phase shifts induced by light. At the molecular level, Nmu-/-Nms-/-Gpr176-/- mice had a reduced induction of Per1 and cFos mRNA expression in the SCN by light and mildly upregulated circadian expression of Per2, Prok2, Rgs16, and Rasl11b. These expressional changes may underlie the phenotype of the Nmu/Nms/Gpr176 knockout mice. Our data argue that there is a mechanism requiring Nmu, Nms, and Gpr176 for the proper modulation of light-induced phase shift in mice. Simultaneous modulation of Nmu/Nms/Gpr176 may provide a potential target option for modulating the circadian clock.

Constant Light, Pdp1, and Tim Exert Influence on Free-Running Period of Locomotor Rhythms in the Cricket Gryllus bimaculatus.

Most insects show circadian rhythms of which the free-running period changes in a light-dependent manner and is generally longer under constant light (LL) than under constant dark conditions in nocturnal animals. However, the mechanism underlying this LL-dependent period change remains unclear. Here, using the cricket Gryllus bimaculatus, we examined the effects of long-term LL exposure on the free-running period of locomotor rhythms. Initially, the free-running period was considerably longer than 24 h but it gradually became shorter during long-term exposure to LL. The initial lengthening and ensuing gradual shortening under long-term LL exposure were observed even after unilateral removal of the optic lobe. Thus, these changes in the free-running period could be attributable to a single optic lobe clock. RNA interference (RNAi)-mediated silencing of the clock genes Par domain protein 1 (Pdp1) and timeless (tim) revealed that the treatments eliminated the initial period lengthening by LL without reducing circadian photoreceptor gene expression. However, they did not affect the period shortening during long-term LL exposure. The slopes of the regression line for the period change during long-term LL for Pdp1RNAi-treated and timRNAi-treated crickets were not different from that of the dsDsRed2-treated control. These results suggest that the initial period lengthening after transfer to LL requires tim and Pdp1, while the ensuing period shortening during long-term LL exposure is caused by a mechanism independent of tim and Pdp1.

Modulation of Cellular Circadian Rhythms by Secondary Metabolites of Lichens.

BackgroundMost mammalian cells harbor molecular circadian clocks that synchronize physiological functions with the 24-h day-night cycle. Disruption of circadian rhythms, through genetic or environmental changes, promotes the development of disorders like obesity, cardiovascular diseases, and cancer. At the cellular level, circadian, mitotic, and redox cycles are functionally coupled. Evernic (EA) and usnic acid (UA), two lichen secondary metabolites, show various pharmacological activities including anti-oxidative, anti-inflammatory, and neuroprotective action. All these effects have likewise been associated with a functional circadian clock.Hypothesis/PurposeTo test, if the lichen compounds EA and UA modulate circadian clock function at the cellular level.MethodsWe used three different cell lines and two circadian luminescence reporter systems for evaluating dose- and time-dependent effects of EA/UA treatment on cellular clock regulation at high temporal resolution. Output parameters studied were circadian luminescence rhythm period, amplitude, phase, and dampening rate.ResultsBoth compounds had marked effects on clock rhythm amplitudes and dampening independent of cell type, with UA generally showing a higher efficiency than EA. Only in fibroblast cells, significant effects on clock period were observed for UA treated cells showing shorter and EA treated cells showing longer period lengths. Transient treatment of mouse embryonic fibroblasts at different phases had only minor clock resetting effects for both compounds.ConclusionSecondary metabolites of lichen alter cellular circadian clocks through amplitude reduction and increased rhythm dampening.

Cercariae of a Bird Schistosome Follow a Similar Emergence Pattern under Different Subarctic Conditions: First Experimental Study.

The emergence of cercariae from infected mollusks is considered one of the most important adaptive strategies for maintaining the trematode life cycle. Short transmission opportunities of cercariae are often compensated by periodic daily rhythms in the cercarial release. However, there are virtually no data on the cercarial emergence of bird schistosomes from freshwater ecosystems in northern latitudes. We investigated the daily cercarial emergence rhythms of the bird schistosome Trichobilharzia sp. “peregra” from the snail host Radix balthica in a subarctic lake under both natural and laboratory seasonal conditions. We demonstrated a circadian rhythm with the highest emergence during the morning hours, being seasonally independent of the photo- and thermo-period regimes of subarctic summer and autumn, as well as relatively high production of cercariae at low temperatures typical of northern environments. These patterns were consistent under both field and laboratory conditions. While light intensity triggered and prolonged cercarial emergence, the temperature had little effect on cercarial rhythms but regulated seasonal output rates. This suggests an adaptive strategy of bird schistosomes to compensate for the narrow transmission window. Our results fill a gap in our knowledge of the transmission dynamics and success of bird schistosomes under high latitude conditions that may serve as a basis for elucidating future potential risks and implementing control measures related to the spread of cercarial dermatitis due to global warming.