268,439 research outputs found

    Self-organization of signal transduction

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    We propose a model of parameter learning for signal transduction, where the objective function is defined by signal transmission efficiency. We apply this to learn kinetic rates as a form of evolutionary learning, and look for parameters which satisfy the objective. This is a novel approach compared to the usual technique of adjusting parameters only on the basis of experimental data. The resulting model is self-organizing, i.e. perturbations in protein concentrations or changes in extracellular signaling will automatically lead to adaptation. We systematically perturb protein concentrations and observe the response of the system. We find compensatory or co-regulation of protein expression levels. In a novel experiment, we alter the distribution of extracellular signaling, and observe adaptation based on optimizing signal transmission. We also discuss the relationship between signaling with and without transients. Signaling by transients may involve maximization of signal transmission efficiency for the peak response, but a minimization in steady-state responses. With an appropriate objective function, this can also be achieved by concentration adjustment. Self-organizing systems may be predictive of unwanted drug interference effects, since they aim to mimic complex cellular adaptation in a unified way.Comment: updated version, 13 pages, 4 figures, 3 Tables, supplemental tabl

    Finite-State Channel Models for Signal Transduction in Neural Systems

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    Information theory provides powerful tools for understanding communication systems. This analysis can be applied to intercellular signal transduction, which is a means of chemical communication among cells and microbes. We discuss how to apply information-theoretic analysis to ligand-receptor systems, which form the signal carrier and receiver in intercellular signal transduction channels. We also discuss the applications of these results to neuroscience.Comment: Accepted for publication in 2016 IEEE International Conference on Acoustics, Speech, and Signal Processing, Shanghai, Chin

    Subsection signal transduction

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    AbstractInteractions between human platelets and human umbilical vein endothelial cells (HUVEC) were studied by monitoring changes in cytosolic [Ca2+]i in both cell types. Confluent monolayers of Fura-2-loaded HUVEC, grown on gelatin-coated coverslips, responded to repeated addition of a suspension of unstimulated platelets by transient increases in cytosolic [Ca2+]i. These platelet-evoked Ca2+ responses were not caused by products secreted from the platelets and were insensitive to inhibitors of platelet activation and/or platelet aggregation. The platelet-evoked rises in [Ca2+]i in endothelial cells, similarly as the thrombin-evoked rises, were blocked by preincubation of HUVEC with the phospholipase C inhibitor U73122 or the Ca2+ influx blocker Ni2+. In contrast, treatment with the protein tyrosine kinase inhibitor genistein was without effect. Video imaging experiments, in which the fluorescence signal was analysed from the individual cells of an endothelial monolayer, showed that only 2ÔÇô20% of the cells, scattered over the monolayer, responded to the addition of platelets by a transient increase in [Ca2+]i, whereas most of the cells responded to thrombin. This leads to the conclusion that unstimulated platelets can activate HUVEC putatively by mechanical interaction with individual endothelial cells in the monolayer

    Ras p21 protein promotes survival and fiber outgrowth of cultured embryonic neurons

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    Although evidence obtained with the PC12 cell line has suggested a role for the ras oncogene proteins in the signal transduction of nerve growth factor-mediated fiber outgrowth, little is known about the signal transduction mechanisms involved in the neuronal response to neurotrophic factors in nontransformed cells. We report here that the oncogene protein T24-ras, when introduced into the cytoplasm of freshly dissociated chick embryonic neurons, promotes the in vitro survival and neurite outgrowth of nerve growth factor-responsive dorsal root ganglion neurons, brain-derived neurotrophic factor-responsive nodose ganglion neurons, and ciliary neuronotrophic factor-responsive ciliary ganglion neurons. The proto-oncogene product c-Ha-ras also promotes neuronal survival, albeit less strongly. No effect could be observed with truncated counterparts of T24-ras and c-Ha-ras lacking the 23 C-terminal amino acids including the membrane-anchoring, palmityl-accepting cysteine. These results suggest a generalized involvement of ras or ras-like proteins in the intracellular signal transduction pathway for neurotrophic factors

    Fold-Hopf Bursting in a Model for Calcium Signal Transduction

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    We study a recent model for calcium signal transduction. This model displays spiking, bursting and chaotic oscillations in accordance with experimental results. We calculate bifurcation diagrams and study the bursting behaviour in detail. This behaviour is classified according to the dynamics of separated slow and fast subsystems. It is shown to be of the Fold-Hopf type, a type which was previously only described in the context of neuronal systems, but not in the context of signal transduction in the cell.Comment: 13 pages, 5 figure

    Signal transduction protocols

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    Making Protein Immunoprecipitates Elaine A. Elion and Yunmei Wang Signal Transduction Inhibitors in Cellular Function Maofu Fu, Chenguang Wang, Xueping Zhang, and Richard G. Pestell Two-Dimensional Gel Electrophoresis for the Identification of Signaling Targets Yukihito Kabuyama, Kirsi K. Polvinen, Katheryn A. Resing, and Natalie G. Ahn A High-Throughput Mammalian Cell-Based Transient Transfection Assay Daniel J. Noonan, Kenneth Henry, and Michelle L. Twaroski Determining Protein Half-Lives Pengbo Zhou Assaying Protein Kinase Activity Jan Brabek and Steven K. Hanks Comparative Phosphorylation Site Mapping From Gel-Derived Proteins Using a Multidimensional ES/MS-Based Approach Francesca Zappacosta, Michael J. Huddleston, and Roland S. Annan Studies of Calmodulin-Dependent Regulation Paul C. Brandt and Thomas C. Vanaman Measurement of Protein-DNA Interactions In Vivo by Chromatin Immunoprecipitation Hogune Im, Jeffrey A. Grass, Kirby D. Johnson, Meghan E. Boyer, Jing Wu, and Emery H. Bresnick Characterization of Protein-DNA Association In Vivo by Chromatin Immunoprecipitation Laurent Kuras Nonradioactive Methods for Detecting Activation of Ras-Related Small G Proteins Douglas A. Andres Nucleocytoplasmic Glycosylation, O-GlcNAc: Identification and Site Mapping Natasha Elizabeth Zachara, Win Den Cheung, and Gerald Warren Hart Techniques in Protein Methylation Jaeho Lee, Donghang Cheng, and Mark T. Bedford Assaying Lipid Phosphate Phosphatase Activities Gil-Soo Han and George M. Carman Assaying Phosphoinositide Phosphatases Gregory S. Taylor and Jack E. Dixon Assaying Phospholipase A2 Activity Christina C. Leslie and Michael H. Gelb Measurement and Immunofluorescence of Cellular Phosphoinositides Hiroko Hama, Javad Torabinejad, Glenn D. Prestwich, and Daryll B. DeWald Measuring Dynamic Changes in cAMP Using Fluorescence Resonance Energy Transfer Sandrine Evellin, Marco Mongillo, Anna Terrin, Valentina Lissandron, and Manuela Zaccolo In Vivo Detection of Protein-Protein Interaction in Plant Cells Using BRET Chitra Subramanian, Yao Xu, Carl Hirschie Johnson, and Albrecht G. von Arnim Revealing Protein Dynamics by Photobleaching Techniques Frank van Drogen and Matthias Peter Assaying Cytochrome c Translocation During Apoptosis Nigel J. Waterhouse, Rohan Steel, Ruth Kluck, and Joseph A. Trapani Inde

    Non-equilibrium phase transitions in biomolecular signal transduction

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    We study a mechanism for reliable switching in biomolecular signal-transduction cascades. Steady bistable states are created by system-size cooperative effects in populations of proteins, in spite of the fact that the phosphorylation-state transitions of any molecule, by means of which the switch is implemented, are highly stochastic. The emergence of switching is a nonequilibrium phase transition in an energetically driven, dissipative system described by a master equation. We use operator and functional integral methods from reaction-diffusion theory to solve for the phase structure, noise spectrum, and escape trajectories and first-passage times of a class of minimal models of switches, showing how all critical properties for switch behavior can be computed within a unified framework
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