Precise transcriptional control of cellular quiescence by BRAVO/WOX5 complex in Arabidopsis roots.

Understanding stem cell regulatory circuits is the next challenge in plant biology, as these cells are essential for tissue growth and organ regeneration in response to stress. In the Arabidopsis primary root apex, stem cell-specific transcription factors BRAVO and WOX5 co-localize in the quiescent centre (QC) cells, where they commonly repress cell division so that these cells can act as a reservoir to replenish surrounding stem cells, yet their molecular connection remains unknown. Genetic and biochemical analysis indicates that BRAVO and WOX5 form a transcription factor complex that modulates gene expression in the QC cells to preserve overall root growth and architecture. Furthermore, by using mathematical modelling we establish that BRAVO uses the WOX5/BRAVO complex to promote WOX5 activity in the stem cells. Our results unveil the importance of transcriptional regulatory circuits in plant stem cell development.

Methods for Modeling Brassinosteroid-Mediated Signaling in Plant Development.

Mathematical modeling of biological processes is a useful tool to draw conclusions that are contained in the data, but not directly reachable, as well as to make predictions and select the most efficient follow-up experiments. Here we outline a method to model systems of a few proteins that interact transcriptionally and/or posttranscriptionally, by representing the system as Ordinary Differential Equations and to study the model dynamics and stationary states. We exemplify this method by focusing on the regulation by the brassinosteroid (BR) signaling component BRASSINOSTEROID INSENSITIVE1 ETHYL METHYL SULFONATE SUPPRESSOR1 (BES1) of BRAVO, a quiescence-regulating transcription factor expressed in the quiescent cells of Arabidopsis thaliana roots. The method to extract the stationary states and the dynamics is provided as a Mathematica code and requires basic knowledge of the Mathematica software to be executed.

Regulation of plant stem cell quiescence by a brassinosteroid signaling module.

The quiescent center (QC) maintains the activity of the surrounding stem cells within the root stem cell niche, yet specific molecular players sustaining the low rate of QC cell division remain poorly understood. Here, we identified a R2R3-MYB transcription factor, BRAVO (BRASSINOSTEROIDS AT VASCULAR AND ORGANIZING CENTER), acting as a cell-specific repressor of QC divisions in the primary root of Arabidopsis. Ectopic BRAVO expression restricts overall root growth and ceases root regeneration upon damage of the stem cells, demonstrating the role of BRAVO in counteracting Brassinosteroid (BR)-mediated cell division in the QC cells. Interestingly, BR-regulated transcription factor BES1 (BRI1-EMS SUPRESSOR 1) directly represses and physically interacts with BRAVO in vivo, creating a switch that modulates QC divisions at the root stem cell niche. Together, our results define a mechanism for BR-mediated regulation of stem cell quiescence in plants.

Asymmetric stochastic switching driven by intrinsic molecular noise.

Low-copy-number molecules are involved in many functions in cells. The intrinsic fluctuations of these numbers can enable stochastic switching between multiple steady states, inducing phenotypic variability. Herein we present a theoretical and computational study based on Master Equations and Fokker-Planck and Langevin descriptions of stochastic switching for a genetic circuit of autoactivation. We show that in this circuit the intrinsic fluctuations arising from low-copy numbers, which are inherently state-dependent, drive asymmetric switching. These theoretical results are consistent with experimental data that have been reported for the bistable system of the gallactose signaling network in yeast. Our study unravels that intrinsic fluctuations, while not required to describe bistability, are fundamental to understand stochastic switching and the dynamical relative stability of multiple states.

Utilización de servicios de salud y flujos asistenciales / Health services provision and geographic accessibility

Este estudio describe la oferta de servicios de salud de Cataluña como parte del análisis de la situación del Mapa Sanitario, fijando un punto de partida para el proceso de adaptación de los servicios a las necesidades de la población. Incluye también un análisis de la accesibilidad geográfica a los centros sanitarios del sistema público de salud mediante la utilización de un sistema de información geográfica (SIG), con variables de georreferenciación y cálculos de distancia y tiempo de desplazamiento, y se exponen sus principales resultados, de los cuales se constata, por un lado, la adecuación de la red asistencial catalana a la distribución de la población, con una elevada proximidad geográfica de los servicios a la población y un alto grado de capilaridad, principalmente en la atención primaria. Por otro lado, se pone de manifiesto la importancia que pueden adquirir las herramientas y procedimientos SIG en la planificación sanitaria

This article analyses the use of healthcare services in Catalonia with reference to their variability and cross-territory healthcare flows. The coefficients of variation show a lower degree of territorial dispersion in acute-care and primary-care hospitalisation, and a greater degree in social-healthcare. In the territorial analysis of the penetration indices, five large attraction poles are salient. There is no significant association among healthcare flows between the specialised healthcare given in acute healthcare hospitals, mental healthcare and social-healthcare,whereas a strong association was observed between the set of services associated to the acute-care hospital structure (hospitalisation, outpatient service and emergency care) and also among the social healthcareinternment services (medium and long-term stays). This would seem to suggest that the association between flows refers to services that are habitually rendered from one single healthcare mechanism, and not so much to a pattern of cross-territory relations

Plasmación territorial de la planificación de servicios de salud: escenarios de referencia para la toma de decisiones compartida sobre desarrollo y adecuación de servicios a escala territorial / The territorial expression of health-service planning: scenarios for shared decision-making on the development and adaptation of services on a territorial level

Para aplicar los criterios de planificación a escala territorial, con un planteamiento prospectivo y teniendo en cuenta las especificidades de cada lugar, en el Mapa Sanitario de Cataluña se han construido escenarios de desarrollo y adecuación de los servicios en el horizonte 2015. La escala territorial es la de los 37 ámbitos en que se ha dividido Cataluña con el objetivo de impulsar una nueva forma de toma de decisiones, descentralizada y participada, a través de los Gobiernos Territoriales de Salud. La nueva organización territorial sanitaria es el substrato que debe permitir articular la relación entre profesionales y servicios que comparten una misma población de referencia. En este artículo se expone la metodología para la construcción de los escenarios y se sintetizan las principales propuestas de actuación que se derivan del Mapa en los 37 territorios indicados. Asimismo, se muestra el contenido detallado de los escenarios territoriales en base a dos casos prácticos

To apply planning criteria on a territorial level, with a forward-looking approach and taking into account the specificities of each location, in the Health Map of Catalonia, scenarios have been constructed for thedevelopment and adaptation of services for the 2015 horizon. The territorial scale is that of the 37 areas into which Catalonia has been divided in order to promote a new form of decentralised, combined decision-making, through the Territorial Health Governments. The new territorial health organisation is the substrate which must enable the relationship between professionals and services that share the same reference population to be coordinated. This article deals with themethodology for constructing the scenarios, and a summary is given of the principal action proposals which arise from the map in the aforementioned 37 territories. Detailed content of the territorial scenarios is also given, based on two practical cases

[Use of health services and healthcare flows]. / Utilización de servicios de salud y flujos asistenciales.

This article analyses the use of healthcare services in Catalonia with reference to their variability and cross-territory healthcare flows. The coefficients of variation show a lower degree of territorial dispersion in acute-care and primary-care hospitalisation, and a greater degree in social-healthcare. In the territorial analysis of the penetration indices, five large attraction poles are salient. There is no significant association among healthcare flows between the specialised healthcare given in acute healthcare hospitals, mental healthcare and social-healthcare, whereas a strong association was observed between the set of services associated to the acute-care hospital structure (hospitalisation, outpatient service and emergency care) and also among the social healthcare internment services (medium and long-term stays). This would seem to suggest that the association between flows refers to services that are habitually rendered from one single healthcare mechanism, and not so much to a pattern of cross-territory relations.

[The territorial expression of health-service planning: scenarios for shared decision-making on the development and adaptation of services on a territorial level]. / Plasmación territorial de la planificación de servicios de salud: escenarios de referencia para la toma de decisiones compartida sobre desarrollo y adecuación de servicios a escala territorial.

To apply planning criteria on a territorial level, with a forward-looking approach and taking into account the specificities of each location, in the Health Map of Catalonia, scenarios have been constructed for the development and adaptation of services for the 2015 horizon. The territorial scale is that of the 37 areas into which Catalonia has been divided in order to promote a new form of decentralised, combined decision- making, through the Territorial Health Governments. The new territorial health organisation is the substrate which must enable the relationship between professionals and services that share the same reference population to be coordinated. This article deals with the methodology for constructing the scenarios, and a summary is given of the principal action proposals which arise from the map in the aforementioned 37 territories. Detailed content of the territorial scenarios is also given, based on two practical cases.