Attractor Metabolic Networks

Background The experimental observations and numerical studies with dissipative metabolic networks have shown that cellular enzymatic activity self-organizes spontaneously leading to the emergence of a Systemic Metabolic Structure in the cell, characterized by a set of different enzymatic reactions always locked into active states (metabolic core) while the rest of the catalytic processes are only intermittently active. This global metabolic structure was verified for Escherichia coli, Helicobacter pylori and Saccharomyces cerevisiae, and it seems to be a common key feature to all cellular organisms. In concordance with these observations, the cell can be considered a complex metabolic network which mainly integrates a large ensemble of self-organized multienzymatic complexes interconnected by substrate fluxes and regulatory signals, where multiple autonomous oscillatory and quasi-stationary catalytic patterns simultaneously emerge. The network adjusts the internal metabolic activities to the external change by means of flux plasticity and structural plasticityMethodology/Principal Findings In order to research the systemic mechanisms involved in the regulation of the cellular enzymatic activity we have studied different catalytic activities of a dissipative metabolic network under different external stimuli. The emergent biochemical data have been analysed using statistical mechanic tools, studying some macroscopic properties such as the global information and the energy of the system. We have also obtained an equivalent Hopfield network using a Boltzmann machine. Our main result shows that the dissipative metabolic network can behave as an attractor metabolic network.Conclusions/Significance We have found that the systemic enzymatic activities are governed by attractors with capacity to store functional metabolic patterns which can be correctly recovered from specific input stimuli. The network attractors regulate the catalytic patterns, modify the efficiency in the connection between the multienzymatic complexes, and stably retain these modifications. Here for the first time, we have introduced the general concept of attractor metabolic network, in which this dynamic behavior is observed.Funding provided by Junta de Andalucia Proyecto de Excelencia P09FQM-4682 and the University-Society grant US11/13 of the UPV/EHU. DAP acknowledges support from project TIN2011-27696-C02-01, Spanish Ministry of Economy and Competitiveness. JMC is supported by Ikerbasque, The Basque Foundation for Science

The competitive nucleation of misfit dislocation dipole and misfit extended dislocation dipole in nanocomposites

Nanocomposites have shown excellent mechanical and physical properties; however, their properties are seriously affected by the nucleation of misfit defects at the interfaces between the inclusion and the matrix. Based on the energy rule, the nucleation criteria for a misfit extended dislocation dipole (MEDD) and a misfit screw dislocation dipole (MSDD) are analytically given. Furthermore, we systematically investigate the effects of the geometrical and mechanical factors, such as the radius of the inclusion, the misfit strain, the shear modulus ratio and the stacking fault energy, on the competitive nucleation between MEDD and MSDD. It is found that the stacking fault energy has a decisive effect on the competitive nucleation of MEDD and MSDD. The critical stacking fault energy for the nucleation transferring from MSDD to MEDD increases with the increase of the shear modulus ratio and decrease of the misfit strain, while it is almost not affected by the inclusion radius

Dual delivery of hydrophilic and hydrophobic drugs from chitosan/diatomaceous earth composite membranes

Oral administration of drugs presents important limitations, which are frequently not granted the importance that they really have. For instance, hepatic metabolism means an important drug loss, while some patients have their ability to swell highly compromised (i.e. unconsciousness, cancer...). Sublingual placement of an accurate Pharmaceutical Dosage Form is an attractive alternative. This work explores the use of the beta-chitosan membranes, from marine industry residues, composed with marine sediments for dual sublingual drug delivery. As proof of concept, the membranes were loaded with a hydrophilic (gentamicin) and a hydrophobic (dexamethasone) drug. The physico-chemical and morphological characterization indicated the successful incorporated of diatomaceous earth within the chitosan membranes. Drug delivery studies showed the potential of all formulations for the immediate release of hydrophilic drugs, while diatomaceous earth improved the loading and release of the hydrophobic drug. These results highlight the interest of the herein developed membranes for dual drug delivery.The research leading to these results has received funding from Erasmus Mundus Joint Programmes, ERDF / POCTEP 2007-2013 under project 0687_NOVOMAR_1_P, from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement number REGPOT-CT2012-316331-POLARIS, and from the North Portugal Regional Operational Programme (ON.2 - O Novo Norte), within the National Strategic Reference Framework (QREN 2007-2013) under the project NORTE-01-0124-FEDER-000018. Portuguese Foundation for Science and Technology is also acknowledged for the post-doctoral fellowship SFRH/BPD/112140/2015, for the doctoral fellowship SFRH/BD/112139/2015 and for the funds provided under the program Investigador FCT 2012 (IF/00423/2012). Dr. Helder Santos (University of Helsinki) is also acknowledged for valuable discussions on the concept.The research leading to these results has received funding from Erasmus Mundus Joint Programmes, ERDF / POCTEP 2007–2013 under project 0687_NOVOMAR_1_P, from the European Union Seventh Framework Programme (FP7/2007–2013) under grant agreement number REGPOT-CT2012-316331-POLARIS, and from the North Portugal Regional Operational Programme (ON.2 – O Novo Norte), within the National Strategic Reference Framework (QREN 2007-2013) under the project NORTE-01-0124-FEDER-000018. Portuguese Foundation for Science and Technology is also acknowledged for the post-doctoral fellowship SFRH/BPD/112140/2015, for the doctoral fellowship SFRH/BD/112139/2015 and for the funds provided under the program Investigador FCT 2012 (IF/00423/2012). Dr. Hélder Santos (University of Helsinki) is also acknowledged for valuable discussions on the concept.info:eu-repo/semantics/publishedVersio