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Leibniz Institute for Farm Animal Biology | FBN · Bioinformatics and Biomathematics

Key points: Maximal endurance performance is greater in the early daytime. Timed exercise differentially alters the muscle transcriptome and (phospho)-proteome. Early daytime exercise triggers energy provisioning and tissue regeneration. Early night-time exercise activates stress-related and catabolic pathways. Scheduled training has limited effec...

Timed physical activity might potentiate the health benefits of training. The underlying signaling events triggered by exercise at different times of the day are, however, poorly understood. Here, we found that time-dependent variations in maximal treadmill exercise capacity of naïve mice were associated with energy stores, mostly hepatic glycogen...

Background: Statistical analyses of biological problems in life sciences often lead to high-dimensional linear models. To solve the corresponding system of equations, penalization approaches are often the methods of choice. They are especially useful in case of multicollinearity, which appears if the number of explanatory variables exceeds the num...

Statistical analyses of biological problems in life sciences often lead to high-dimensional linear models. To solve the corresponding system of equations, penalisation approaches are often the methods of choice. They are especially useful in case of multicollinearity which appears if the number of explanatory variables exceeds the number of observa...

Periodicity in nematode egg excretion may be of evolutionary origin as it can favour dispersal of the eggs in the environment. We investigated whether egg excretion by Heterakis gallinarum shows a repeatable pattern of periodicity. The faecal egg concentration and total number of eggs excreted within 4-h intervals were significantly affected by the...

Significance Rhythms in gene expression propelled by the circadian clock and environmental signals are ubiquitous across cells and tissues. In particular, in mouse tissues, thousands of transcripts show oscillations with a period of 24 hours. Keys question are how such rhythms propagate and eventually exert functions, but also how these are generat...

Genome biology approaches have made enormous contributions to our understanding of biological rhythms, particularly in identifying outputs of the clock, including RNAs, proteins, and metabolites, whose abundance oscillates throughout the day. These methods hold significant promise for future discovery, particularly when combined with computational...

troponin; kidney diseases

Significance Circadian (24-h) rhythms influence the behavior and physiology of many organisms. These rhythms are generated at the gene expression level, causing the waxing and waning of protein abundances. Metabolic enzymes are affected, but the principles for the propagation of enzyme rhythmicity to cellular metabolism as quantified by fluxes thro...

Author Circadian rhythms switch gene expression on and off with a daily rhythm in most tissues in mammals and other animals. Typically, thousands of genes are affected, and the functions of these rhythms include preparing and adjusting various physiological functions in tissues to meet time-of-day dependent requirements optimally. The controllers...

Motivation: Biological rhythms, such as rhythms in gene expression controlled by the cell cycle or the circadian clock, are important in cell physiology. A common type of experiment compares rhythmicity in tissues or cells either kept under different conditions or having different genotypes. Such investigations provide insights into underlying mec...

Circadian clocks synchronize organisms to the 24 h rhythms of the environment. These clocks persist under constant conditions, have their origin at the cellular level, and produce an output of rhythmic mRNA expression affecting thousands of transcripts in many mammalian cell types. Here, we review the charting of circadian output rhythms in mRNA ex...

The rich mammalian cellular circadian output affects thousands of genes in many cell types and has been the subject of genome-wide transcriptome and proteome studies. The results have been enigmatic because transcript peak abundances do not always follow the peaks of gene-expression activity in time. We posited that circadian degradation of mRNAs a...

A fundamental problem in research on biological rhythms is that of detecting and assessing the significance of rhythms in large sets of data. Classic methods based on Fourier theory are often hampered by the complex and unpredictable characteristics of experimental and biological noise. Robust nonparametric methods are available but are limited to...

Circadian clocks are autonomous oscillators entrained by external Zeitgebers such as light-dark and temperature cycles. On the cellular level, rhythms are generated by negative transcriptional feedback loops. In mammals, the suprachiasmatic nucleus (SCN) in the anterior part of the hypothalamus plays the role of the central circadian pacemaker. Cou...

In addition to the well-known circadian rhythms in animal behavior, cell biology, and gene expression, there are also 12 hr rhythms. The mechanism giving rise to these 12 hr rhythms is not clear. We worked with the hypothesis that observed 12 hr rhythms in gene expression are the results of an interplay between components of the circadian clock. An...

The circadian clock is accountable for the regulation of internal rhythms in most living organisms. It allows the anticipation of environmental changes during the day and a better adaptation of physiological processes. In mammals the main clock is located in the suprachiasmatic nucleus (SCN) and synchronizes secondary clocks throughout the body. It...

Circadian clocks are endogenous oscillators driving daily rhythms in physiology and behavior. Synchronization of these timers to environmental light-dark cycles ('entrainment') is crucial for an organism's fitness. Little is known about which oscillator qualities determine entrainment, i.e., entrainment range, phase and amplitude. In a systematic t...

Author Summary Earth's 24-h-rotation around its axis is mirrored in the circadian clock that resides within each of our cells, controlling expression of ∼10% of all genes. The circadian clock is constructed as a negative feedback loop, in which clock proteins inhibit their own synthesis. During the last decade, a picture has emerged in which each c...

Adipose tissue may contain few large adipocytes (hypertrophy) or many small adipocytes (hyperplasia). We investigated factors of putative importance for adipose tissue morphology. Subcutaneous adipocyte size and total fat mass were compared in 764 subjects with BMI 18-60 kg/m(2). A morphology value was defined as the difference between the measured...

Obesity is increasing in an epidemic manner in most countries and constitutes a public health problem by enhancing the risk for cardiovascular disease and metabolic disorders such as type 2 diabetes. Owing to the increase in obesity, life expectancy may start to decrease in developed countries for the first time in recent history. The factors deter...

The liver regenerates and maintains its function and size after injury by counterbalancing cell death with compensatory cell division. During liver regeneration, injured sites release cytokines, which stimulate normally quiescent hepatocytes to re-enter cell division cycle. Using a mesoscale approach, we have implemented the first mathematical mode...

Human beings exhibit wide variation in their timing of daily behavior. We and others have suggested previously that such differences might arise because of alterations in the period length of the endogenous human circadian oscillator. Using dermal fibroblast cells from skin biopsies of 28 subjects of early and late chronotype (11 “larks” and 17 “ow...

Virtually all living organisms have evolved a circadian (~24 hour) clock that controls physiological and behavioural processes with exquisite precision throughout the day/night cycle. The suprachiasmatic nucleus (SCN), which generates these ~24 h rhythms in mammals, consists of several thousand neurons. Each neuron contains a gene-regulatory networ...

Regulated degradation of circadian clock proteins is a crucial step for rhythm generation per se but also for establishing a normal circadian period. Here, the authors show that the F-box protein beta-transducin repeat containing protein 1 (beta-TrCP1) as part of the E3 ubiquitin ligase complex is an essential component of the mammalian circadian o...

Obesity is increasing in an epidemic fashion in most countries and constitutes a public health problem by enhancing the risk for cardiovascular disease and metabolic disorders such as type 2 diabetes. Owing to the increase in obesity, life expectancy may start to decrease in developed countries for the first time in recent history. The factors dete...

The pancreatic beta-cells respond to an increased glycolytic flux by secreting insulin. The signal propagation goes via mitochondrial metabolism, which relays the signal to different routes. One route is an increased ATP production that, via ATP-sensitive K(+) (K(ATP)) channels, modulates the cell membrane potential to allow calcium influx, which t...

PERIOD (PER) proteins are central components within the mammalian circadian oscillator, and are believed to form a negative feedback complex that inhibits their own transcription at a particular circadian phase. Phosphorylation of PER proteins regulates their stability as well as their subcellular localization. In a systematic screen, we have ident...

The Pyrosequencing technology is a newly developed DNA sequencing method that monitors DNA nucleotide incorporation in real-time. A set of coupled enzymatic reactions, together with bioluminescence, detects incorporated nucleotides in the form of light pulses, yielding a characteristic light profile. In this study, a biochemical model of the Pyrose...

We have constructed a model of the upper part of the glycolysis in the pancreatic beta-cell. The model comprises the enzymatic reactions from glucokinase to glyceraldehyde-3-phosphate dehydrogenase (GAPD). Our results show, for a substantial part of the parameter space, an oscillatory behavior of the glycolysis for a large range of glucose concentr...