Frequency of elemental events of intracellular Ca²⁺ dynamics

The dynamics of intracellular Ca²⁺ is driven by random events called Ca²⁺ puffs, in which Ca²⁺ is liberated from intracellular stores. We show that the emergence of Ca²⁺ puffs can be mapped to an escape process. The mean first passage times that correspond to the stochastic fraction of puff periods are computed from a novel master equation and two Fokker-Planck equations. Our results demonstrate that the mathematical modeling of Ca²⁺ puffs has to account for the discrete character of the Ca²⁺ release sites and does not permit a continuous description of the number of open channels.

Sensitisation waves in a bidomain fire-diffuse-fire model of intracellular Ca²⁺ dynamics

We present a bidomain threshold model of intracellular calcium (Ca²⁺) dynamics in which, as suggested by recent experiments, the cytosolic threshold for Ca²⁺ liberation is modulated by the Ca²⁺ concentration in the releasing compartment. We explicitly construct stationary fronts and determine their stability using an Evans function approach. Our results show that a biologically motivated choice of a dynamic threshold, as opposed to a constant threshold, can pin stationary fronts that would otherwise be unstable. This illustrates a novel mechanism to stabilise pinned interfaces in continuous excitable systems. Our framework also allows us to compute travelling pulse solutions in closed form and systematically probe the wave speed as a function of physiologically important parameters. We find that the existence of travelling wave solutions depends on the time scale of the threshold dynamics, and that facilitating release by lowering the cytosolic threshold increases the wave speed. The construction of the Evans function for a travelling pulse shows that of the co-existing fast and slow solutions the slow one is always unstable.

Sostenibilidad de los servicios de salud en el área No. 6, Centro de Salud Hospital de Baba, Los Ríos, año 2001

El proceso de investigación buscará determinar si los servicios de salud brindados a la población que pertenecen al área n. 6, Centro de Salud Hospital Baba, de la provincia de Los Ríos, tiene una sustentación económica y pueden seguir siendo entregados a la población geográfica de la zona, determinando además los problemas que sobre acceso a los servicios d salud tenga la comunidad del área.-au

El agua en la tradición lírica manierista: ríos y mares en las "Flores" de Pedro Espinosa (1605)

El presente trabajo aborda el recorrido del agua como imagen poética en sus dos principales manifestaciones —aguas dulces y saladas— en las "Flores de poetas ilustres de España" (1605), antología lírica ordenada por el antequerano Pedro Espinosa paradigmática del manierismo literario español. Desde la cita erudita hasta el símbolo, pasando por el particular tratamiento de la tópica clásica y petrarquista que le sirve de sustancia en un contexto contrarreformista, así como por la característica personificación de ríos y mares que distingue a la obra, se hace patente el protagonismo otorgado a este elemento tanto en la selección de textos como en su disposición y en la particular elocución de la retórica del movimiento. Como sucede con los juegos de agua del jardín manierista, integrando el agua de modo sustancial en su estética intelectualizante y preciosista y en sus diseños geométricos, el libro ofrece la oportunidad como ninguna otra de nuestra literatura áurea de apreciar la innovadora significación y versatilidad de este elemento como motivo poético.

Phosphodiesterase 6 generates intracellular cGMP microdomains in the native endothelium

Endothelial cells (EC) are essential regulator of vascular homeostasis through the generation and release of various bioactive agents, including nitric oxide (NO). NO modulates several vascular functions such as vascular tone and permeability, through the stimulation of soluble guanylate cyclase (sGC) leading to the production of cGMP. Conversely, phosphodiesterases (PDEs) are enzymes metabolizing cyclic nucleotides (cGMP and cAMP) and are therefore major regulatory players for cGMP and cAMP signalling pathways. Although ECs are the main source of NO, little is known on the endothelial NO-cGMP signalling pathway and cellular outcomes. It was then hypothesized that a specific population of cGMP-phosphodiesterases allows ECs to stabilize cGMP levels despite the elevated production of NO. Expression of cGMP-phosphodiesterases was initially studied in resistance mesenteric arteries from mice. PDE5 and PDE6 were both found at mRNA and protein levels in native arteries but PDE6 is not found in cultured ECs. Interestingly, subcellular distributions of both enzymes were distinct. PDE5 appeared to be homogeneously distributed whilst PDE6 catalytic subunits (PDE6 and PDE6) showed a preferential staining in the perinuclear region. These results suggest that PDE6 might be involved in the regulation of cGMP microdomains. Based on these findings, a mathematical model was developed. Simulations of dynamic cGMP levels in ECs support the notion of cGMP microdomains dependent on PDE6 expression and localization. In the absence of PDE6, application of NO either as a single bolus or repetitive pulses led to a homogeneous increase in cGMP levels in ECs despite PDE5 homogeneous distribution. However, PDE6 subcellular targeting to the perinuclear membrane generated a cGMP-depleted perinuclear space. The findings from this study provide the first evidence of the expression and specific intracellular distribution of PDE6 in native endothelial cells that strongly support their involvement in the generation of cGMP microdomains

Intracellular signaling and trafficking in cancer: Role of Rab5-GTPases in migration and invasion of breast cancer cells

Metastasis is characterized pathologically by uncontrolled cell invasion, proliferation, migration and angiogenesis. Steroid hormones, such as estrogen, and growth factors, which include insulin growth factor I/II (IGF-1/IGF-2) therapy has been associated with most if not all of the features of metastasis. It has been determined that IGF-1 increases cell survival of cancer cells and potentiate the effect of E2 and other ligand growth factors on breast cancer cells. However not much information is available that comprehensively expounds on the roles of insulin growth factor receptor (IGFR) and Rab GTPases may play in breast cancer. The latter, Rab GTPases, are small signaling molecules and critical in the regulation of many cellular processes including cell migration, growth via the endocytic pathway. This research involves the role of Rab GTPases, specifically Rab5 and its guanine exchange factors (GEFs), in the promotion of cancer cell migration and invasion. Two important questions abound: Are IGFR stimulation and downstream effect involved the endocytic pathway in carcinogenesis? What role does Rab5 play in cell migration and invasion of cancer cells? The hypothesis is that growth factor signaling is dependent on Rab5 activity in mediating the aggressiveness of cancer cells. The goal is to demonstrate that IGF-1 signaling is dependent on Rab5 function in breast cancer progression. Here, the results thus far, have shown that while activation of Rab5 may mediate increased cell proliferation, migration and invasion in breast cancer cells, the Rab5 GEF, RIN1 interacts with the IGFR thereby facilitating migration and invasion activities in breast cells. Furthermore, endocytosis of the IGFR in breast cancer cells seems to be caveolin dependent as the data has shown. This taken together, the data shows that IGF-1 signaling in breast cancer cells relies on IGF-1R phosphorylation, caveolae internalization and sequestration to the early endosome RIN1 function and Rab5 activation.^

Phosphodiesterase 6 generates intracellular cGMP microdomains in the native endothelium

Endothelial cells (EC) are essential regulator of vascular homeostasis through the generation and release of various bioactive agents, including nitric oxide (NO). NO modulates several vascular functions such as vascular tone and permeability, through the stimulation of soluble guanylate cyclase (sGC) leading to the production of cGMP. Conversely, phosphodiesterases (PDEs) are enzymes metabolizing cyclic nucleotides (cGMP and cAMP) and are therefore major regulatory players for cGMP and cAMP signalling pathways. Although ECs are the main source of NO, little is known on the endothelial NO-cGMP signalling pathway and cellular outcomes. It was then hypothesized that a specific population of cGMP-phosphodiesterases allows ECs to stabilize cGMP levels despite the elevated production of NO. Expression of cGMP-phosphodiesterases was initially studied in resistance mesenteric arteries from mice. PDE5 and PDE6 were both found at mRNA and protein levels in native arteries but PDE6 is not found in cultured ECs. Interestingly, subcellular distributions of both enzymes were distinct. PDE5 appeared to be homogeneously distributed whilst PDE6 catalytic subunits (PDE6 and PDE6) showed a preferential staining in the perinuclear region. These results suggest that PDE6 might be involved in the regulation of cGMP microdomains. Based on these findings, a mathematical model was developed. Simulations of dynamic cGMP levels in ECs support the notion of cGMP microdomains dependent on PDE6 expression and localization. In the absence of PDE6, application of NO either as a single bolus or repetitive pulses led to a homogeneous increase in cGMP levels in ECs despite PDE5 homogeneous distribution. However, PDE6 subcellular targeting to the perinuclear membrane generated a cGMP-depleted perinuclear space. The findings from this study provide the first evidence of the expression and specific intracellular distribution of PDE6 in native endothelial cells that strongly support their involvement in the generation of cGMP microdomains

The decrease of NAD(P)H:quinone oxidoreductase 1 activity and increase of ROS production by NADPH oxidases are early biomarkers in doxorubicin cardiotoxicity

info:eu-repo/semantics/publishedVersion

Cellular ROS imaging with hydro-Cy3 dye is strongly influenced by mitochondrial membrane potential

Background: Hydrocyanines are widely used as fluorogenic probes to monitor reactive oxygen species (ROS) generation in cells. Their brightness, stability to autoxidation and photobleaching, large signal change upon oxidation, pH independence and red/near infrared emission are particularly attractive for imaging ROS in live tissue. Methods: Using confocal fluorescence microscopy we have examined an interference of mitochondrial membrane potential (ΔΨm) with fluorescence intensity and localisation of a commercial hydro-Cy3 probe in respiring and non-respiring colon carcinoma HCT116 cells. Results: We found that the oxidised (fluorescent) form of hydro-Cy3 is highly homologous to the common ΔΨm-sensitive probe JC-1, which accumulates and aggregates only in ‘energised’ negatively charged mitochondrial matrix. Therefore, hydro-Cy3 oxidised by hydroxyl and superoxide radicals tends to accumulate in mitochondrial matrix, but dissipates and loses brightness as soon as ΔΨm is compromised. Experiments with mitochondrial inhibitor oligomycin and uncoupler FCCP, as well as a common ROS producer paraquat demonstrated that signals of the oxidised hydro-Cy3 probe rapidly and strongly decrease upon mitochondrial depolarisation, regardless of the rate of cellular ROS production. Conclusions: While analysing ROS-derived fluorescence of commercial hydrocyanine probes, an accurate control of ΔΨm is required. General significance: If not accounted for, non-specific effect of mitochondrial polarisation state on the behaviour of oxidised hydrocyanines can cause artefacts and data misinterpretation in ROS studies.

Rapamycin reverses age-related increases in mitochondrial ROS production at complex I, oxidative stress, accumulation of mtDNA fragments inside nuclear DNA, and lipofuscin level, and increases autophagy, in the liver of middle-aged mice

Rapamycin consistently increases longevity in mice although the mechanism of action of this drug is unknown. In the present investigation we studied the effect of rapamycin on mitochondrial oxidative stress at the same dose that is known to increase longevity in mice (14 mg of rapamycin/kg of diet). Middle aged mice (16 months old) showed significant age-related increases in mitochondrial ROS production at complex I, accumulation of mtDNA fragments inside nuclear DNA, mitochondrial protein lipoxidation, and lipofuscin accumulation compared to young animals (4 months old) in the liver. After 7 weeks of dietary treatment all those increases were totally or partially (lipofuscin) abolished by rapamycin, middle aged rapamycin-treated animals showing similar levels in those parameters to young animals. The decrease in mitochondrial ROS production was due to qualitative instead of quantitative changes in complex I. The decrease in mitochondrial protein lipoxidation was not due to decreases in the amount of highly oxidizable unsaturated fatty acids. Rapamycin also decreased the amount of RAPTOR (of mTOR complex) and increased the amounts of the PGC1-α and ATG13 proteins. The results are consistent with the possibility that rapamycin increases longevity in mice at least in part by lowering mitochondrial ROS production and increasing autophagy, decreasing the derived final forms of damage accumulated with age which are responsible for increased longevity. The decrease in lipofuscin accumulation induced by rapamycin adds to previous information suggesting that the increase in longevity induced by this drug can be due to a decrease in the rate of aging. © 2016 Elsevier Inc.

VALORACIÓN ECONÓMICA DE LOS RECURSOS HÍDRICOS EN LAS CUENCAS DE LOS RÍOS BANANO Y BANANITO

Entre los meses de marzo y setiembre del 2004, el Centro Internacional en Política Económica para el Desarrollo Sostenible de la Universidad Nacional (CINPE-UNA) elaboró el estudio Valoración económica de los recursos hI’dricos en las cuencas de los rfos Banano y Bananito3 . El objetivo general de éste responde a “estimar el valor del recurso hídrico en las cuencas de los ríos Banano y Bananito, en función de los usos prioritarios, para la recomendación de mecanismos efectivos para la sostenibilidad de un sistema de compensación por los servicios hidrológicos”. Para cumplir con este objetivo se plantean los siguientes objetivos específicos: (1) identificar el método de valoración económica para el recurso hídrico más apropiado dadas las condiciones de la zona, (2) cuantificar los servicios hidrológicos en las cuencas de los ríos Banano y Bananito en función de los principales usos, y (3) recomendar un mecanismo de pago voluntario por el servicio ambiental hídrico, basado en los resultados del estudio, que provea al Área de Conservación La Amistad Caribe (ACLA-C) los elementos para el desarrollo de una experiencia concreta.Producto de una exhaustiva revisión bibliográfica y dados los objetivos del estudio se seleccionó el Análisis de Múltiples Criterios (AMC), como la metodología marco para la valoración económica. Esto implica la aplicación de un método no tradicional, que permite combinar variables cuantitativas y cualitativas. A este respecto, el uso de una metodología participativa y multisectorial hizo posible la participación de los principales grupos de actores usuarios del agua. que se clasificaron en cinco grupos: (1) Asociaciones Administradoras de Acueductos Rurales (ASADAS) y acueductos rurales, (2) ONG’s y organizaciones comunales, (3) sociedad civil, (4) empresa privada y (5) sector público.Luego de sistematizar la información recabada durante las 23 sesiones de consulta participativa. se procede al análisis de los datos, que sirven de insumos para realizar la valoración económica y, finalmente, el diseño de la propuesta de mecanismos de cobro por grupo de usuarios para el pago por servicios ambientales. Los resultados finales se presentan mediante el uso de matrices y gráficos de telaraña.Este informe presenta los avances correspondientes al primer objetivo específico. Asimismo, incluye los comentarios y las sugerencias realizadas durante y posterior al taller de discusión con representantes de PROARCA-APM, TNC y ACLA-C. El documento contiene la caracterización económica y social del área en estudio, una revisión de estudios de valoración, y métodos, así como el método de valoración seleccionado y su forma de aplicación.A bstract:Between March and September 2004, the International Center of Economic Policy for Sustainable Development of the National University (CINPE.IJNA) elaborated the study Economic Valuation of ihe Water Resources in ihe Basins of ihe rivers Banano and Bananito4. The general objcctive of it answers to “estimate the value of the water resource in the basin of the rivers Banano and Bananito, depending on the prior uses, for the recommendation of effective mechanisms for the sustainability of a system of compensation for the hydrological serv ices”.The following specific objectives appear to reach the general objective: (1) To identify the most appropriate method of economic valuation for water resource given (he conditions of the zone. (2) To quantify the hydrological services in the basins of the rivers Banano and Bananito depending on (he principal uses. And (3) to recommend a mechanism of voluntary payment for the environmental water service based on the results of the study, which provides to La Amistad Caribe Conservation Area (ACLA-C), the elements for the development of a concrete experience.Product and given of an exhaustive bibliographical review, the Analysis of Multiple Criteria (AMC) is selected as (he methodology for the economic valuation. It implies (he application of a not traditional method, which allows combining quantitative and qualitative variables. In this regard, the use of a participatory methodoiogy there made possible the participation of the principal groups of actors users of the water, who quatified ¡n five groups to knowing, (1) administrative associations of rural aqueducts (ASADAS), (2) ONG and communal organizations, (3) civil society, (4) private sector and (5) public sector.After systematizing the information obtained during 23 meetings of participatory consultation. one proceeds to the analysis of the information, which use as ¡nputs to realize the economic valuation. Finally, the design of the offer of collection mechanisms for user group for the payment for environmental services is presented. The final results appear by means of the use of counterfoils and spider web graphs.This repon includes the commentaries and suggestions realized during and later to ihe workshop of discussion with representatives of PROARCA-APM, TNC and ACLA-C. The document also contains the economic and social characterization of the area under study, a review of studies of valuation, and methods. as well as the method of valuation selected and its form of application.

UN PLAN PARA RECUPERAR LOS RÍOS Y ACUÍFEROS DEL VALLE CENTRAL

El mayor consumo de agua en Costa Rica ocurre en el Valle Central, pues ahíestá asentada cerca del 60% de la población del país. Sin embargo, la disponibilidad de agua está disminuyendo debido al crecimiento demográfico y al decreciente volumen de los ríos y aguas subterráneas.El Valle Central posee cerca de 57 ríos que podrían utilizarse como fuente de agua potable. pero sólo 10 de ellos tienen sus nacientes ubicadas en bosques primarios y son adecuadas para este fin. Las nacientes de la mayoría de los otros ríos se encuentran en tierras económicamente improductivas, tales como pastizales y áreas de bosques muy alterados, que pierden su volumen de agua durante la estación seca.Las proyecciones de crecimiento demográfico hasta el año 2100 permiten visualizar un marcado incremento en la demanda de agua, el cual se mantendrá durante los próximos 50 años. Consecuentemente, para proporcionar un adecuado suministro de agua para esta creciente población. es fundamental detener la contaminación de las aguas subterráneas y recobrar el volumen de agua de los ríos.En este trabajo se propone un plan sencillo para aumentar el volumen de agua de los ríos del Valle Central y para proteger nuestros acuíferos. Se mencionan también otros beneficios económicos y sociales que tendría la aplicación de esta propuesta.Abstract: About 60% of the popuiation of Costa Rica lives in the Central Valley where consequcntly occurs the highest water consumption. As a contrast water shortness is increasing in this country due to population growth and diminishing volume of river and subterranean water.There are about 57 rivers in the Central Valley that could be used as a source of water but only 10 of them have their headwaters inside primary forest and are appropriate for this purpose. The headwaters of mosi of the nvers lay in underproductive lands such as grass fields and very disturbed forest and bose their water volume during dry season.Population growth estimates until year 2100 allow foreseeing a high rate of increase in water demand for the next 50 years. In order to have an adequate supply of water for ihis expanding population it is mandatory to stop subterranean water pollution and to recovcr nver water volume.In this paper 1 propose a simple plan to augment the water volume of the headwaters of the rivers of the Central Valley and to protect our subterranean water sources. Other social and economic benefits that stem from this plan are also analyzed.

SENSORES REMOTOS FOTOGRÁFICOS: ZONIFICACIÓN POR INUNDACIONES EN LAS CUENCAS BAJAS DE LOS RÍOS PARRITA Y LIMONCITO: UNA CARACTERIZACIÓN SOCIOESPACIAL MEDIANTE FOTOS AEREAS Y MAPAS

Usando procedimientos de trabajo con fotos aéreas de diferentes años, se analiza en el caso de la ciudad de Limón el avance del poblamiento hacia áreas costeras sujetas a inundaciones. Una vez diseñado el mapa que muestra para cuatro períodos la información extraída de las fotos aéreas, se realiza-un análisis físico –social de las condiciones  que dan origen a la vulnerabilidad al riesgo por inundación. En el caso del poblado de Parrita, se reconstruyen con ayuda de fotos aéreas, los distintos cursos fluviales que el río Parrita ha formado en un período de toma fotográfica aérea para cuatro años diferentes. Una vez dibujado este documento, se efectúa un análisis sobre las áreas de mayor riesgo por inundaciones, evaluando los aspectos sociales y económicos de la población afectada.  SUMMARY Using aerial photographs of different years, we analyze in the case of the Limon city, the growth population in coastal areas affected by flooding. A map showing four periods of aerial photointerpretation, fieldwork and another sources, gives information about the physical and social conditions of some areas with vulnerability by flooding. In the case of Parrita town, the use of aerial photographs of four periods, make it possible to know the geomorphological dynamic of Parrita river. With this map, we evaluate the risk by flooding, taking into account the social and economical aspects of the affected population.

EL IMPACTO HUMANO SOBRE LAS POBLACIONES DE TRUCHAS EN LOS RÍOS DE VARA BLANCA DE HEREDIA

Este estudio es el proyecto de una investigación sobre el impacto del uso y manejo de la tierra en la región de Vara Blanca referente a las poblaciones de truchas en los ríos. Fue cumplido a través de entrevistas con 54 habitantes de la región y cuestionarios de 31 pescadores del área de San José, las cuales muestran su actitud y sus conocimientos sobre las leyes. Como una parte del estudio se analizaron las políticas relacionadas con el Ministerio de Agricultura y Ganadería en los departamentos de Acuacultura, de Vida Silvestre y de Reservas Forestales, estos dos últimos de la Dirección General Forestal. La situación actual del manejo sobre los ríos que tienen truchas, muestra una deficiencia en ciertos aspectos; sobre la divulgación de leyes hacia la gente del campo, información técnica para promulgar leyes, y educación de la guardia rural encargada de hacer cumplir las leyes de pesca. Un análisis de las aguas en relación con la temperatura, oxígeno disuelto, dióxido de carbono y acidez muestra que las aguas en los ríos tenían una calidad adecuada durante marzo y abril de 1984. Además, una observación de la condición de la tierra a lo largo de los ríos fue cumplida y los resultados demostraron una carencia de un uso apropiado de la tierra, que se debe a la falta de conocimiento o desinterés por parte de los pobladores del área para mantener la producción de truchas en los ríos

Hoja Tres Ríos: Uso de la Tierra

Proyecto de Actualización Cartográfica de usos de la Tierra a escala 1:10.000 GAM de Costa Rica. Elaboración de Cartografía digital y Ortofotos.