Mammals evolved an endogenous timing system to coordinate their physiology and behaviour to the 24h period of the solar day. While it is well accepted that circadian rhythms are generated by intracellular transcriptional feedback loops, it is still debated which network motifs are necessary and sufficient for generating self-sustained oscillations. Here, we systematically explore a data-based circadian oscillator model with multiple negative and positive feedback loops and identify a series of three subsequent inhibitions known as “repressilator” as a core element of the mammalian circadian oscillator. The central role of the repressilator motif is consistent with time-resolved ChIP-seq experiments of circadian clock transcription factors and loss of rhythmicity in core clock gene knockouts.

Circadian rhythms govern multiple aspects of animal metabolism. Transcriptome-, proteome-and metabolome-wide measurements have revealed widespread circadian rhythms in metabolism governed by a cellular genetic oscillator, the circadian core clock. However, it remains unclear if and under which conditions transcriptional rhythms cause rhythms in particular metabolites and metabolic fluxes. Here, we analyzed the circadian orchestration of metabolic pathways by direct measurement of enzyme activities, analysis of transcriptome data, and developing a theoretical method called circadian response analysis. Contrary to a common assumption, we found that pronounced rhythms in metabolic pathways are often favored by separation rather than alignment in the times of peak activity of key enzymes. This property holds true for a set of metabolic pathway motifs (e.g., linear chains and branching points) and also under the conditions of fast kinetics typical for metabolic reactions. By circadian response analysis of pathway motifs, we determined exact timing separation constraints on rhythmic enzyme activities that allow for substantial rhythms in pathway flux and metabolite concentrations. Direct measurements of circadian enzyme activities in mouse skeletal muscle confirmed that such timing separation occurs in vivo.circadian rhythms | glucose metabolism | metabolic response analysis | mouse skeletal muscle C ircadian rhythms are ∼24-h cycles in behavior, physiology, and cellular processes that persist in the absence of external cues. In mammals, circadian rhythms in the expression of thousands of genes in various metabolic tissues ensure up-or down-regulation of important metabolic processes in anticipation of daily activity and rest periods (1, 2). Circadian gene expression in mammalian tissues depends on the circadian core clock, a genetic feedback oscillator inducing the transcription of thousands of clock-controlled genes. Additional rhythmicity in gene expression is generated by rhythmic posttranscriptional regulation (3). Circadian rhythms have been detected in mRNA and protein abundances (4-6), enzyme activities (7, 8), and concentrations of metabolites (9-11) in various mammalian tissues. Whereas the mechanisms underlying rhythmic gene expression are relatively well-studied, it remains unclear how circadian gene expression induces rhythms in the abundance of metabolites or metabolic fluxes.A naïve picture of circadian regulation (Fig. 1A) ("central dogma of molecular chronobiology") suggests that the circadian core clock drives rhythmic mRNA expression, resulting in rhythmic protein levels and directly leading to rhythmic enzyme activity (12) and thus, metabolic activity. Here, especially metabolic pathway flux (rate of conversion of substrate into product metabolites measured in concentration per time; an analogy is water flow through a floodgate) has been regarded as a crucial biological function under strong evolutionary selection pressure (13,14). However, it is unclear whether circadian abundances of enzyme trans...

Priming, an inducible stress defence strategy that prepares an organism for an impending stress event, is common in microbes and has been studied mostly in isolated organisms or populations. How the benefits of priming change in the microbial community context and, vice versa, whether priming influences competition between organisms, remain largely unknown. In this study, we grew different isolates of soil fungi that experienced heat stress in isolation and pairwise competition experiments and assessed colony extension rate as a measure of fitness under priming and non-priming conditions. Based on this data, we developed a cellular automaton model simulating the growth of the ascomycete Chaetomium angustispirale competing against other fungi and systematically varied fungal response traits to explain similarities and differences observed in the experimental data. We showed that competition changes the priming benefit compared with isolated growth and that it can even be reversed depending on the competitor's traits such as growth rate, primeability and stress susceptibility. With this study, we transfer insights on priming from studies in isolation to competition between species. This is an important step towards understanding the role of inducible defences in microbial community assembly and composition.

Organisms are prone to different stressors and have evolved various defense mechanisms. One such defense mechanism is priming, where a mild preceding stress prepares the organism toward an improved stress response. This improved response can strongly vary, and primed organisms have been found to respond with one of three response strategies: a shorter delay to stress, a faster buildup of their response or a more intense response. However, a universal comparative assessment, which response is superior under a given environmental setting, is missing. We investigate the benefits of the three improved responses for microorganisms with an ordinary differential equation model, simulating the impact of an external stress on a microbial population that is either naïve or primed. We systematically assess the resulting population performance for different costs associated with priming and stress conditions. Our results show that independent of stress type and priming costs, the stronger primed response is most beneficial for longer stress phases, while the faster and earlier responses increase population performance and survival probability under short stresses. Competition increases priming benefits and promotes the early stress response. This dependence on the ecological context highlights the importance of including primed response strategies into microbial stress ecology.

Abstract. Mosses are a major component of the arctic vegetation, particularly in wetlands. We present C ∕ N atomic ratio, δ13C and δ15N data of 400 brown-moss samples belonging to 10 species that were collected along hydrological gradients within polygonal mires located on the southern Taymyr Peninsula and the Lena River delta in northern Siberia. Additionally, n-alkane patterns of six of these species (16 samples) were investigated. The aim of the study is to see whether the inter- and intraspecific differences in C ∕ N, isotopic compositions and n-alkanes are indicative of habitat, particularly with respect to water level. Overall, we find high variability in all investigated parameters for two different moisture-related groups of moss species. The C ∕ N ratios range between 11 and 53 (median: 32) and show large variations at the intraspecific level. However, species preferring a dry habitat (xero-mesophilic mosses) show higher C ∕ N ratios than those preferring a wet habitat (meso-hygrophilic mosses). The δ13C values range between −37.0 and −22.5 ‰ (median  =  −27.8 ‰). The δ15N values range between −6.6 and +1.7 ‰ (median  =  −2.2 ‰). We find differences in δ13C and δ15N compositions between both habitat types. For some species of the meso-hygrophilic group, we suggest that a relationship between the individual habitat water level and isotopic composition can be inferred as a function of microbial symbiosis. The n-alkane distribution also shows differences primarily between xero-mesophilic and meso-hygrophilic mosses, i.e. having a dominance of n-alkanes with long (n-C29, n-C31) and intermediate (n-C25) chain lengths, respectively. Overall, our results reveal that C ∕ N ratios, isotopic signals and n-alkanes of studied brown-moss taxa from polygonal wetlands are characteristic of their habitat.