Information theoretical study of cross-talk mediated signal transduction in MAPK pathways

Biochemical networks related to similar functional pathways are often correlated due to cross-talk among the homologous proteins in the different networks. Using a stochastic framework, we address the functional significance of the cross-talk between two pathways. Our theoretical analysis on generic MAPK pathways reveals cross-talk is responsible for developing coordinated fluctuations between the pathways. The extent of correlation evaluated in terms of the information theoretic measure provides directionality to net information propagation. Stochastic time series and scattered plot suggest that the cross-talk generates synchronization within a cell as well as in a cellular population. Depending on the number of input and output, we identify signal integration and signal bifurcation motif that arise due to inter-pathway connectivity in the composite network. Analysis using partial information decomposition quantifies the net synergy in the information propagation through these branched pathways.Comment: Revised version, 17 pages, 5 figure

Role of relaxation time scale in noisy signal transduction

Intracellular fluctuations, mainly triggered by gene expression, are an inevitable phenomenon observed in living cells. It influences generation of phenotypic diversity in genetically identical cells. Such variation of cellular components is beneficial in some contexts but detrimental in others. To quantify the fluctuations in a gene product, we undertake an analytical scheme for studying few naturally abundant linear as well as branched chain network motifs. We solve the Langevin equations associated with each motif under the purview of linear noise approximation and quantify Fano factor and mutual information. Both quantifiable expressions exclusively depend on the relaxation time (decay rate constant) and steady state population of the network components. We investigate the effect of relaxation time constraints on Fano factor and mutual information to indentify a time scale domain where a network can recognize the fluctuations associated with the input signal more reliably. We also show how input population affects both quantities. We extend our calculation to long chain linear motif and show that with increasing chain length, the Fano factor value increases but the mutual information processing capability decreases. In this type of motif, the intermediate components are shown to act as a noise filter that tune up input fluctuations and maintain optimum fluctuations in the output. For branched chain motifs, both quantities vary within a large scale due to their network architecture and facilitate survival of living system in diverse environmental conditions.Comment: 14 pages, 6 figure

Influence of Needle-punching Parameters for the Preparation of Polypyrrole-coated Non-woven Composites for Heat Generation

This work deals with the preparation and characterization of electrically conductive needle-punched non-woven composites for heat generation. Electro-conductive non-woven composites were prepared through the in situ chemical polymerization of pyrrole with FeCl3 (oxidant) and p-toluene sulfonic acid (dopant). A two-stage double-bath process was adopted for the in situ chemical polymerization of pyrrole. The effect of parameters such as fibre fineness, needle-punching density and depth of needle punching on a polypyrrole add-on, and surface resistivity were studied by employing the Box-Behnken response surface design. It was observed that fibre fineness was the most influential parameter of the polypyrrole add-on. The lowest surface resistivity of the polypyrrole coated sample (200 g/m2, prepared with a punch density of 200 punch/cm2, a punching depth of 6 mm and fibre fineness of 2.78 dtex) was found to be 9.32 kΩ/□ with a polypyrrole add-on of 47.93%. This non-woven composite demonstrated good electrical conductivity and exhibited Joule’s effect of heat generation. Due to the application of a 30 V DC power supply, the surface temperature of the non-woven composite rose to 55 ºC from a room temperature of 37 ºC. Optical and electron microscopy images of the non-woven composites showed that PPy molecules formed a uniform coating on the non-woven surface. FTIR studies evidenced the coating of PPy on a polyester surface. These coated non-woven composites were highly electrically conductive and practically useful for the fabrication of heating pads for therapeutic use

HPLC OF PHENOLIC COMPOUNDS, ANTIOXIDANT AND ANTIMICROBIAL ACTIVITY OF BULBS FROM THREE ORNITHOGALUM SPECIES AVAILABLE IN INDIA

Objective: The aim of the study was to analyze phenolic compounds of three species of Ornithogalum viz Ornithogalum virens, Ornithogalum thyrsoides, Ornithogalum dubium and to assess their bioactivity in terms of antimicrobial and antioxidant potential.Methods: Extracts were prepared in 20% aqueous methanol. Each extract was subjected to phenolic and flavonoid estimation. Antioxidant activity was tested using DPPH method, and their antimicrobial activity was tested on six pathogenic strains namely Enterobacter cloacae, Serratia marcescens, Escherichia coli, Shigella dysenteriae, Staphylococcus aureus and Pseudomonas aeruginosa. The extracts were subjected to HPLC analysis with different standards namely gallic acid, caffeic acid, p-coumaric acid, syringic acid, sinapic acid, ferulic acid, methyl gallate, catechin, rutin, apigenin, quercetin, myricetin, and kaempherol.Results: O. dubium was found to have highest antioxidant activity (IC50 311 µg/g extract). Inhibition zone was minimum in S. marcescens and E. coli on the application of extracts of O. virens, and the consequent MIC was 670 µg and 650µg/g dry weight respectively. None of the three extracts was found to have any effect either on S. aureus or P. aeruginosa. HPLC analyses have shown that myricetin was the primary flavonoid constituent of the extract of O. dubium and gallic acid of O. virens.Conclusion: O. dubium shows maximum antioxidant and antimicrobial activity. Extracts of O. virens also shows maximum polyphenol content. From the HPLC results, it is evident that the flavonoids present in O. dubium are myricetin, rutin, p-coumaric acid along with some phenolic compounds, which confers bioactivity to the extract.Keywords: Ornithogalum, Phenolic acid, Flavonoids, HPLC, Antioxidant activity, Antimicrobial activit

Information Theoretical Study of Cross-Talk Mediated Signal Transduction in MAPK Pathways

Biochemical networks having similar functional pathways are often correlated due to cross-talk among the homologous proteins in the different networks. Using a stochastic framework, we address the functional significance of the cross-talk between two pathways. A theoretical analysis on generic MAPK pathways reveals cross-talk is responsible for developing coordinated fluctuations between the pathways. The extent of correlation evaluated in terms of the information theoretic measure provides directionality to net information propagation. Stochastic time series suggest that the cross-talk generates synchronisation in a cell. In addition, the cross-interaction develops correlation between two different phosphorylated kinases expressed in each of the cells in a population of genetically identical cells. Depending on the number of inputs and outputs, we identify signal integration and signal bifurcation motif that arise due to inter-pathway connectivity in the composite network. Analysis using partial information decomposition, an extended formalism of multivariate information calculation, also quantifies the net synergy in the information propagation through the branched pathways. Under this formalism, signature of synergy or redundancy is observed due to the architectural difference in the branched pathways

Role of Relaxation Time Scale in Noisy Signal Transduction

<div><p>Intra-cellular fluctuations, mainly triggered by gene expression, are an inevitable phenomenon observed in living cells. It influences generation of phenotypic diversity in genetically identical cells. Such variation of cellular components is beneficial in some contexts but detrimental in others. To quantify the fluctuations in a gene product, we undertake an analytical scheme for studying few naturally abundant linear as well as branched chain network motifs. We solve the Langevin equations associated with each motif under the purview of linear noise approximation and derive the expressions for Fano factor and mutual information in close analytical form. Both quantifiable expressions exclusively depend on the relaxation time (decay rate constant) and steady state population of the network components. We investigate the effect of relaxation time constraints on Fano factor and mutual information to indentify a time scale domain where a network can recognize the fluctuations associated with the input signal more reliably. We also show how input population affects both quantities. We extend our calculation to long chain linear motif and show that with increasing chain length, the Fano factor value increases but the mutual information processing capability decreases. In this type of motif, the intermediate components act as a noise filter that tune up input fluctuations and maintain optimum fluctuations in the output. For branched chain motifs, both quantities vary within a large scale due to their network architecture and facilitate survival of living system in diverse environmental conditions.</p></div

Schematic presentation of different GTRN motifs.

<p>(a) one step cascade (OSC), (b) two step cascade (TSC), (c) multi step cascade with <i>n</i> number of intermediate nodes, (d) OR coherent feed forward loop (OCFFL), (e) AND coherent feed forward loop (ACFFL) and (f) incoherent feed forward loop (ICFFL).</p

The OCFFL.

<p>(a) Fano factor and (b) mutual information (<i>s</i>, <i>y</i>) profiles as a function of S dependent synthesis rate constant </p><p></p><p></p><p>k3′</p><p></p><p></p> of Y component. The relations <p></p><p></p><p>k1</p>/<p>τs</p><p>−1</p><p></p>=<p>k2</p>/<p>τx</p><p>−1</p><p></p>=10<p></p><p></p>, <p></p><p>(10</p><p>k3</p>+<p>k3′</p>)/<p>τy</p><p>−1</p><p></p>=10<p></p><p></p> and <p></p><p></p><p>τy</p><p>−1</p><p></p>=10<p></p><p></p> min⁻¹ are maintained so that steady state population of all the components remain unaltered. In both plots, for solid (with open circles), dashed (with open upward triangle), dotted (with open downward triangle) and dash dotted (with open diamond) lines we have used <p></p><p></p><p>τs</p><p>−1</p><p></p>=<p>τx</p><p>−1</p><p></p>=0.1<p></p><p></p> min⁻¹, <p></p><p></p><p>τs</p><p>−1</p><p></p>=<p>τx</p><p>−1</p><p></p>/10=0.1<p></p><p></p> min⁻¹, <p></p><p></p><p>τs</p><p>−1</p><p></p>/100=<p>τx</p><p>−1</p><p></p>=0.1<p></p><p></p> min⁻¹ and <p></p><p></p><p>τs</p><p>−1</p><p></p>=<p>τx</p><p>−1</p><p></p>/100=0.1<p></p><p></p> min⁻¹, respectively. The symbols are generated using stochastic simulation algorithm [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0123242#pone.0123242.ref064" target="_blank">64</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0123242#pone.0123242.ref065" target="_blank">65</a>] and the lines are due to theoretical calculation. In the plot of mutual information the red and black symbols are due to <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0123242#pone.0123242.e015" target="_blank">Eq (7)</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0123242#pone.0123242.e016" target="_blank">Eq (8)</a>, respectively.<p></p