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Van Beek J.H.G.M.,VU University Amsterdam | Supandi F.,VU University Amsterdam | Gavai A.K.,Netherlands Consortium for Systems Biology | Gavai A.K.,VU University Amsterdam | And 4 more authors.
Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences | Year: 2011

The human physiological system is stressed to its limits during endurance sports competition events.We describe a whole body computational model for energy conversion during bicycle racing. About 23 per cent of the metabolic energy is used for muscle work, the rest is converted to heat. We calculated heat transfer by conduction and blood flow inside the body, and heat transfer from the skin by radiation, convection and sweat evaporation, resulting in temperature changes in 25 body compartments. We simulated a mountain time trial to Alpe d'Huez during the Tour de France. To approach the time realized by Lance Armstrong in 2004, very high oxygen uptake must be sustained by the simulated cyclist. Temperature was predicted to reach 39°C in the brain, and 39.7°C in leg muscle. In addition to the macroscopic simulation, we analysed the buffering of bursts of high adenosine triphosphate hydrolysis by creatine kinase during cyclical muscle activity at the biochemical pathway level. To investigate the low oxygen to carbohydrate ratio for the brain, which takes up lactate during exercise, we calculated the flux distribution in cerebral energy metabolism. Computational modelling of the human body, describing heat exchange and energy metabolism, makes simulation of endurance sports events feasible. This journal is © 2011 The Royal Society. Source


Schmitz J.P.J.,TU Eindhoven | Vanlier J.,TU Eindhoven | van Riel N.A.W.,TU Eindhoven | Jeneson J.A.L.,Netherlands Consortium for Systems Biology | And 2 more authors.
Critical Reviews in Biomedical Engineering | Year: 2011

Mitochondria are the power plant of the heart, burning fat and sugars to supply the muscle with the adenosine triphosphate (ATP) free energy that drives contraction and relaxation during each heart beat. This function was first captured in a mathematical model in 1967. Today, interest in such a model has been rekindled by ongoing in silico integrative physiology efforts such as the Cardiac Physiome project. Here, the status of the field of computational modeling of mitochondrial ATP synthetic function is reviewed. © 2011 by Begell House, Inc. Source


Astola L.,Wageningen University | Stigter H.,Wageningen University | Van Dijk A.D.J.,Wageningen University | Van Daelen R.,Netherlands Consortium for Systems Biology | And 2 more authors.
PLoS ONE | Year: 2014

The architecture of tomato inflorescence strongly affects flower production and subsequent crop yield. To understand the genetic activities involved, insight into the underlying network of genes that initiate and control the sympodial growth in the tomato is essential. In this paper, we show how the structure of this network can be derived from available data of the expressions of the involved genes. Our approach starts from employing biological expert knowledge to select the most probable gene candidates behind branching behavior. To find how these genes interact, we develop a stepwise procedure for computational inference of the network structure. Our data consists of expression levels from primary shoot meristems, measured at different developmental stages on three different genotypes of tomato. With the network inferred by our algorithm, we can explain the dynamics corresponding to all three genotypes simultaneously, despite their apparent dissimilarities. We also correctly predict the chronological order of expression peaks for the main hubs in the network. Based on the inferred network, using optimal experimental design criteria, we are able to suggest an informative set of experiments for further investigation of the mechanisms underlying branching behavior. © 2014 Astola et al. Source


Lange K.,Wageningen University | Hugenholtz F.,Wageningen University | Jonathan M.C.,Wageningen University | Schols H.A.,Wageningen University | And 6 more authors.
Molecular Nutrition and Food Research | Year: 2015

Scope: The aim of our study was to investigate and compare the effects of five fibers on the mucosal transcriptome, together with alterations in the luminal microbiota composition and SCFA concentrations in the colon. Methods and results: Mice were fed fibers that differed in carbohydrate composition or a control diet for 10 days. Colonic gene expression profiles and luminal microbiota composition were determined by microarray techniques, and integrated using multivariate statistics. Our data showed a distinct reaction of the host and microbiota to resistant starch, a fiber that was not completely fermented in the colon, whereas the other fibers induced similar responses on gene expression and microbiota. Consistent associations were revealed between fiber-induced enrichment of Clostridium cluster IV and XIVa representatives, and changes in mucosal expression of genes related to energy metabolism. The nuclear receptor PPAR-γ was predicted to be an important regulator of the mucosal responses. Conclusion: Results of this exploratory study suggest that despite different sources and composition, fermentable fibers induce a highly similar mucosal response that may at least be partially governed by PPAR-γ. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source


de Jong J.,Netherlands Cancer Institute | Akhtar W.,Netherlands Consortium for Systems Biology | Akhtar W.,Netherlands Cancer Institute | Badhai J.,Netherlands Cancer Institute | And 9 more authors.
PLoS Genetics | Year: 2014

The ability of retroviruses and transposons to insert their genetic material into host DNA makes them widely used tools in molecular biology, cancer research and gene therapy. However, these systems have biases that may strongly affect research outcomes. To address this issue, we generated very large datasets consisting of ~120000 to ~180000 unselected integrations in the mouse genome for the Sleeping Beauty (SB) and piggyBac (PB) transposons, and the Mouse Mammary Tumor Virus (MMTV). We analyzed ~80 (epi)genomic features to generate bias maps at both local and genome-wide scales. MMTV showed a remarkably uniform distribution of integrations across the genome. More distinct preferences were observed for the two transposons, with PB showing remarkable resemblance to bias profiles of the Murine Leukemia Virus. Furthermore, we present a model where target site selection is directed at multiple scales. At a large scale, target site selection is similar across systems, and defined by domain-oriented features, namely expression of proximal genes, proximity to CpG islands and to genic features, chromatin compaction and replication timing. Notable differences between the systems are mainly observed at smaller scales, and are directed by a diverse range of features. To study the effect of these biases on integration sites occupied under selective pressure, we turned to insertional mutagenesis (IM) screens. In IM screens, putative cancer genes are identified by finding frequently targeted genomic regions, or Common Integration Sites (CISs). Within three recently completed IM screens, we identified 7%-33% putative false positive CISs, which are likely not the result of the oncogenic selection process. Moreover, results indicate that PB, compared to SB, is more suited to tag oncogenes. © 2014 de Jong et al. Source

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