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Emergence of macroscopic simplicity from the Tumor Necrosis Factor-alpha signaling dynamics Nature Precedings
Kentaro Hayashi; Vincent Piras; Masaru Tomita; Masa Tsuchiya; Kumar Selvarajoo.
The Tumor Necrosis Factor-α (TNF-α), a cytokine produced during the innate immune response to invading pathogens, is involved in numerous fundamental cellular processes. Here, to understand the temporal activation profiles of the TNF-α regulated signaling network, we developed a dynamic computational model based on the perturbation-response approach and the law of information (signaling flux) conservation. Our simulations show that the temporal average population response of the TNF-α stimulated transcription factors NF-κB and AP-1, and 3 groups of 180 downstream gene expressions follow first-order equations. Using the model, in contrast to a well-known previous study, our model suggests that the continuous...
Tipo: Manuscript Palavras-chave: Immunology; Bioinformatics.
Ano: 2011 URL: http://precedings.nature.com/documents/6495/version/1
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Signaling Flux Redistribution concept can switch survival to apoptosis in cancer cells Nature Precedings
Daiki Yamada; Kentaro Hayashi; Vincent Piras; Masaru Tomita; Masa Tsuchiya; Kumar Selvarajoo.
The tumor necrosis factor related apoptosis-inducing ligand (TRAIL) induces apoptosis in certain types of carcinoma. However, in majority of malignant tumors, it has no effect. Here we analyzed cell survival and apoptotic pathways triggered by TRAIL. A computational model based on perturbation-response approach with mass-action equations was developed. All 48 parameter values of the model were selected by genetic algorithm that minimizes deviation between experimental and simulation data for human fibrosarcoma cells. Subsequently, we show in silico knock-down of a cell survival pathway molecule could potentially enhance the activation of apoptosis through Signaling Flux Redistribution (SFR).
Tipo: Poster Palavras-chave: Cancer; Immunology; Molecular Cell Biology; Bioinformatics.
Ano: 2010 URL: http://precedings.nature.com/documents/4375/version/1
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