An Approach to the Engineering of Cellular Models Based on P Systems

Living cells assembled into colonies or tissues communicate using complex systems. These systems consist in the interaction between many molecular species distributed over many compartments. Among the different cellular processes used by cells to monitor their environment and respond accordingly, gene regulatory networks, rather than individual genes, are responsible for the information processing and orchestration of the appropriate response [16]. In this respect, synthetic biology has emerged recently as a novel discipline aiming at unravelling the design principles in gene regulatory systems by synthetically engineering transcriptional networks which perform a specific and prefixed task [2]. Formal modelling and analysis are key methodologies used in the field to engineer, assess and compare different genetic designs or devices. In order to model cellular systems in colonies or tissues one requires a formalism able to represent the following relevant features: – Single cells should be described as the elementary units in the system. Nevertheless, they cannot be represented as homogeneous points as they exhibit complex structures containing different compartments where specific molecular species interact according to particular reactions. – The molecular interactions taking place in cellular systems are inherently discrete and stochastic processes. This is a key feature of cellular systems that needs to be taken into account when describing their dynamics [9]. – It has been postulated that gene regulatory networks are organised in a modular manner in such a way that cellular processes arise from the orchestrated interactions between different genetic transcriptional units that can be considered separable modules [1]. – Spatial and geometric information must be represented in the system in order to describe processes involving pattern formation. In this work we review recent advances in the use of the computational paradigm membrane computing or P systems as a formal methodology in synthetic biology for the specification and analysis on cellular system models according to the previously presented points

Membrane Computing as a Modeling Framework. Cellular Systems Case Studies

Membrane computing is a branch of natural computing aiming to abstract computing models from the structure and functioning of the living cell, and from the way cells cooperate in tissues, organs, or other populations of cells. This research area developed very fast, both at the theoretical level and in what concerns the applications. After a very short description of the domain, we mention here the main areas where membrane computing was used as a framework for devising models (biology and bio-medicine, linguistics, economics, computer science, etc.), then we discuss in a certain detail the possibility of using membrane computing as a high level computational modeling framework for addressing structural and dynamical aspects of cellular systems. We close with a comprehensive bibliography of membrane computing applications

Evolution of Daily Gene Co-expression Patterns from Algae to Plants

Daily rhythms play a key role in transcriptome regulation in plants and microalgae orchestrating responses that, among other processes, anticipate light transitions that are essential for their metabolism and development. The recent accumulation of genome-wide transcriptomic data generated under alternating light:dark periods from plants and microalgae has made possible integrative and comparative analysis that could contribute to shed light on the evolution of daily rhythms in the green lineage. In this work, RNA-seq and microarray data generated over 24 h periods in different light regimes from the eudicot Arabidopsis thaliana and the microalgae Chlamydomonas reinhardtii and Ostreococcus tauri have been integrated and analyzed using gene co-expression networks. This analysis revealed a reduction in the size of the daily rhythmic transcriptome from around 90% in Ostreococcus, being heavily influenced by light transitions, to around 40% in Arabidopsis, where a certain independence from light transitions can be observed. A novel Multiple Bidirectional Best Hit (MBBH) algorithm was applied to associate single genes with a family of potential orthologues from evolutionary distant species. Gene duplication, amplification and divergence of rhythmic expression profiles seems to have played a central role in the evolution of gene families in the green lineage such as Pseudo Response Regulators (PRRs), CONSTANS-Likes (COLs), and DNA-binding with One Finger (DOFs). Gene clustering and functional enrichment have been used to identify groups of genes with similar rhythmic gene expression patterns. The comparison of gene clusters between species based on potential orthologous relationships has unveiled a low to moderate level of conservation of daily rhythmic expression patterns. However, a strikingly high conservation was found for the gene clusters exhibiting their highest and/or lowest expression value during the light transitions

El urbanismo en Huelva: territorio y ciudad

El urbanismo en Huelva: Territorio y ciudad. Se inicia con un planteamiento general de cómo mejorar el diseño urbano de nuestras ciudades y como debemos enfocar el modelo de reflexión para conseguir una ciudad soñada, con las condiciones intrínsecas de su propio modelo de ciudad, que la hagan única y diferente, consiguiendo una ciudad mejor, con las directrices de ciudad inteligente, que beneficien a los ciudadanos y mejore su calidad de vida, haciendo la ciudad más competitiva y atractiva para su visita y descubrimiento, mediante la creación y la puesta en valor de sus espacios naturales, espacios públicos y su patrimonio histórico. Como metodología se plantean las áreas de conocimiento utilizadas para el cambio estratégico de la ciudad, de valor patrimonial cultural y territorial, encontrándose la ciudad de Huelva dentro de las ciudades que necesitan un cambo de estrategias, para su transformación en ciudades más amables y confortables para los ciudadanos que la habitan, basándose principalmente en un nuevo enfoque de los espacios colectivos. El espacio público se plantea como un motor de la regeneración urbana e influencia de aspectos concretos como lo lúdico, el deporte o la movilidad en el diseño. Para ello se plantea un marco teórico basado en la crisis del modelo urbanístico actual, de las herramientas de planificación para el diseño de nuestras ciudades, de las leyes normativas para la generación de la ordenación futura de las ciudades, con una estructura tan encorsetada que no deja libertad para el diseño de nuestras ciudades, fruto de sus condicionantes paisajísticos o de sus características históricas dentro de su patrimonio cultural obtenido en su evolución natural. Con esta crisis del urbanismo se deben de plantear nuevas ideas para construir un urbanismo alternativo, un urbanismo no basado en el crecimiento ni en la reutilización del modelo existente, mediante un nuevo enfoque de modelo en ciudades más competitivas y atractivas para su uso. Con todas estas propuestas de reflexión se intenta recuperar esta imagen perdida de ciudad, refrescando la memoria para la obtención de un futuro mejor para la ciudad de Huelva, donde encontremos oportunidades, reciclaje, mejoras y un cambio de actitud en la planificación futura de Huelva, que vaya acompañada de los nuevos aires de cambios que hagan de la ciudad un espacio más eficiente y sostenible para los ciudadanos. El conjunto arquitectónico de la ciudad de Huelva se encuentra situado entre los márgenes de los estuarios del Odiel y del Tinto, al oeste y al este de la ciudad, respectivamente. Dichos estuarios, popularmente conocidos como rías, son junto a los "cabezos" una seña de identidad propia que hace de Huelva un lugar excepcional desde el punto de vista de su patrimonio natural. La armonía del paisaje como interacción entre la Luz, la Biosfera y la Geosfera dota a la ciudad de Huelva de un recurso natural que bien merece la pena ser valorado por la sociedad del siglo XXI y por aquellas generaciones futuras.Urban planning in Huelva: Territory and city. begins with a general exposition of how to improve the urban design of our cities and as we must focus the model of reflection to obtain a dreamed city, with the intrinsic conditions of his own model of city, which make her the only and different, obtaining a better city, with the directives of intelligent city, which they benefit to the citizens and improve his quality of life, doing the most competitive and attractive city for his visit and discovery, by means of the creation and the putting in value of his natural spaces, public spaces and his historical heritage. Since methodology there appear the areas of knowledge used for the strategic change of the city, of patrimonial cultural and territorial value, being the city of Huelva inside the cities that need a cambo of strategies, for his transformation in more nice and comfortable cities for the citizens who live it, being based principally on a new approach of the collective spaces. The public space appears as an engine of the urban regeneration and influence of concrete aspects as the playful thing, the sport or the mobility in the design. For it there appears a theoretical frame based on the crisis of the urban development current model, of the tools of planning for the design of our cities, of the normative laws for the generation of the future arrangement of the cities, with a he structures so encorsetada that it does not leave freedom for the design of our cities, fruit of his determining landscape ones or of his historical characteristics inside his cultural heritage obtained in his natural evolution. With this crisis of the urbanism they must raise new ideas to construct an alternative urbanism, an urbanism not based on the growth not in the reutilization of the existing model, by means of a model new approach in more competitive and attractive cities for his use. With all these offers of reflection one tries to recover this lost image of city, refreshing the memory for the obtaining of the best future for the city of Huelva, where we find opportunities, recycling, improvements and a change of attitude in the future planning of Huelva, which is accompanied of the new airs of changes that do of the city a more efficient and sustainable space for the citizens. The architectural set of the city of Huelva is placed between the margins of the estuaries of the Odiel and of the Red wine, in the western part and to the east of the city, respectively. The above mentioned estuaries, popularly known since laugh, they are close to the "summits" a sign of own identity that does of Huelva an exceptional place from the point of view of his natural heritage. The harmony of the landscape like interaction between the Light, the Biosphere and the Geosfera provides to the city of Huelva of a natural resource that well is worth being valued by the company of the XXI century and by those future generations. This work contemplates the creation and the putting in value of a natural space inserted in the city that uses as point of meeting for the reflection inspired by the Nature and supported by a concept of architectural sustainable innovation. When there is thought about an urban development development that it can change the architectural concept of city, necessarily we have to think about actions that throughout the years, are valid and allow us to manage the use of the area, from the understanding of the natural processes that affect them. In this respect, these lines must serve to exhibit on the one hand: a) The signs of identity. b) The historical value of the city. c) The slogan of city opposite to the sea. Really, we might say that Huelva - points at different horizons and, in each of these horizons, we find the expression of the history of the city throughout the years, esculpiendo an exceptional work that is worth being put in value, to preserve it and to admire her. The city of Huelva has received as legacy of the Nature the "summits" and them "laugh", and to put them in value we have to understand and know them to be able to transmit this value to the future generations them, with the firm offer of which the city of Huelva looks to her laugh

An evolutionarily conserved DOF-CONSTANS module controls plant photoperiodic signaling

© 2015 American Society of Plant Biologists. All Rights Reserved. The response to daylength is a crucial process that evolved very early in plant evolution, entitling the early green eukaryote to predict seasonal variability and attune its physiological responses to the environment. The photoperiod responses evolved into the complex signaling pathways that govern the angiosperm floral transition today. The Chlamydomonas reinhardtii DNA-Binding with One Finger (CrDOF) gene controls transcription in a photoperiod-dependent manner, and its misexpression influences algal growth and viability. In short days, CrDOF enhances CrCO expression, a homolog of plant CONSTANS (CO), by direct binding to its promoter, while it reduces the expression of cell division genes in long days independently of CrCO. In Arabidopsis (Arabidopsis thaliana), transgenic plants overexpressing CrDOF show floral delay and reduced expression of the photoperiodic genes CO and FLOWERING LOCUS T. The conservation of the DOF-CO module during plant evolution could be an important clue to understanding diversification by the inheritance of conserved gene toolkits in key developmental programs.Peer Reviewe

A Study of the Robustness of the EGFR Signalling Cascade Using Continuous Membrane Systems

Many approaches to anticancer treatment have had a limited success. A fundamental hurdle to cancer therapy is the robustness of the signalling networks involved in tumourgenesis. The complexity of net- works of biological signalling pathways is such that the development of simplifying models is essential in trying to understand the wide-ranging cellular responses they can generate. In this paper a model of the epider- mal growth factor receptor signalling cascade is developed using contin- uous membrane systems. This model is used to study the robustness of this signalling cascade which is known to play a key role in tumour cell proliferation, angiogenesis and metastasis.Ministerio de Ciencia y Tecnología TIC2002-04220-C03-0

A CLIPS Simulator for Recognizer P Systems with Active Membranes

In this paper we propose a new way to represent recognizer P systems with active membranes based on Production Systems techniques. This representation allows us to express the set of rules and the configurations in each step of the evolution as facts in a knowledge base. We provide a CLIPS program to simulate the evolutions of this variant of P systems.Ministerio de Ciencia y Tecnología TIC2002-04220-C03-0

Modelling gene expression control using P systems: The Lac Operon, a case study

In this paper P systems are used as a formal framework for the specification and simulation of biological systems. In particular, we will deal with gene regulation systems consisting of protein–protein and protein–DNA interactions that take place in different compartments of the hierarchical structure of the living cell or in different individual cells from a colony. We will explicitly model transcription and translation as concurrent and discrete processes using rewriting rules on multisets of objects and strings. Our approach takes into account the discrete character of the components of the system, its random behaviour and the key role played by membranes in processes involving signalling at the cell surface and selective uptake of substances from the environment. Our systems will evolve according to an extension of Gillespie’s algorithm, called Multicompartmental Gillespie’s Algorithm. The well known gene regulation system in the Lac Operon in Escherichia coli will be modelled as a case study to benchmark our approach.Ministerio de Ciencia y Tecnología TIN2005-09345-C04-0

Attacking the Common Algorithmic Problem by Recognizer P Systems

Many NP-complete problems can be viewed as special cases of the Common Algorithmic Problem (CAP). In a precise sense, which will be defined in the paper, one may say that CAP has a property of local universality. In this paper we present an effective solution to the decision version of the CAP using a family of recognizer P systems with active membranes. The analysis of the solution presented here will be done from the point of view of complexity classes in P systems.Ministerio de Ciencia y Tecnología TIC2002-04220-C03-0

A Model of the Quorum Sensing System in Vibrio fischeri Using P Systems

Quorum sensing is a cell density dependent gene regulation system that allows an entire population of bacterial cells to communicate in order to regulate the expression of certain or specific genes in a coordinated way depending on the size of the population. In this paper we present a model of the Quorum Sensing System in Vibrio fischeri using a variant of membrane systems called P systems. In this framework each bacterium and the environment are represented by membranes and the rules are applied according to an extension of Gillespie’s Algorithm called Multicompartmental Gillespie’s Algorithm. This algorithm runs on more than one compartment and takes into account the disturbance produced when chemical substances diffuse from one compartment or region to another. Our approach allows us to examine the individual behaviour of each bacterium as an agent as well as the emergent behaviour of the colony as a whole and the processes of swarming and recruitment. Our simulations show that at low cell densities bacteria remain dark while at high cell densities some bacteria start to produce light and a recruitment process takes place that makes the whole colony of bacteria to emit light. Our computational modelling of quorum sensing could provide insights that may enable researchers to develop new applications where multiple agents need to robustly and efficiently coordinate their collective behaviour based only on a very limited information of the local environment