Mechanisms of endothelial cell protection by blockade of the JAK2 pathway

10 pages, 7 figures.Inhibition of the JAK2/STAT pathway has been implicated recently in cytoprotective mechanisms in both vascular smooth muscle cells and astrocytes. The advent of JAK2-specific inhibitors provides a practical tool for the study of this pathway in different cellular types. An interest in finding methods to improve endothelial cell (EC) resistance to injury led us to examine the effect of JAK2/STAT inhibition on EC protection. Furthermore, the signaling pathways involved in JAK2/STAT inhibition-related actions were examined. Our results reveal, for the first time, that blockade of JAK2 with the tyrosine kinase inhibitor AG490 strongly protects cultured EC against cell detachment-dependent death and serum deprivation and increases reseeding efficiency. Confirmation of the specificity of the effects of JAK2 inhibition was attained by finding protective effects on transfection with a dominant negative JAK2. Furthermore, AG490 blocked serum deprivation-induced phosphorylation of JAK2. In terms of mechanism, treatment with AG490 induces several relevant responses, both in monolayer and detached cells. These mechanisms include the following: 1) Increase and nuclear translocation of the active, dephosphorylated form of beta-catenin. In functional terms, this translocation is transcriptionally active, and its protective effect is further supported by the stimulation of EC cytoprotection by transfectionally induced excess of beta-catenin. 2) Increase of platelet endothelial cell adhesion molecule (PECAM)/CD31 levels. 3) Increase in total and phosphorylated AKT. 4) Increase in phosphorylated glycogen synthase kinase (GSK)3alpha/beta. The present findings imply potential practical applications of JAK2 inhibition on EC. These applications affect not only EC in the monolayer but also circulating detached cells and involve mechanistic interactions not previously described.This study was supported by grants from the Instituto de Salud Carlos III (Red Cardiovascular), Fondo de Investigaciones Sanitarias (FIS: PI: 030888), Comunidad Autónoma de Madrid (CAM: GR/SAL/0418/2004), Sociedad Española de Nefrología and Instituto Reina Sofía de Investigación Nefrológica (IRSIN, Entrecanales Trust), the Spanish Ministry of Education, Science and Technology (SAF04-00361), Fundación Jiménez Díaz-Capio and Amgen (Barcelona, Spain). M. A. Castilla and F. R. González-Pacheco are investigators from FIS and CAM, respectively. S. Peñate is a senior research technician from Red Cardiovascular (RECAVA), and J. J. P. Deudero is a fellow from the Instituto Carlos III. F. Neria, A. J. de Solis, and R. Fernández-Sánchez are fellows from Fundación C. Rábago. H. Peinado is supported by a grant from Justesa Imagen SA.Peer reviewe

Conservation program works as an alternative irrigation districts in sustainable water management of agricultural use

Water scarcity is an issue of worldwide concern since it is already having an impact on social development. Mexico is not an exception to this problem because in several regions of the country are great difficulties in supplying water, primarily for agricultural use. In Sinaloa, it had been mentioned repeatedly by the media that in the Irrigation District 063, located in the northern of the state, there are problems of water scarcity, and yet there still exist difficulties in conserving the resource. More than 49% of the water used for agriculture is wasted. To resolve this problem, producers and government agencies spend significant resources for investment in water conservation. However, the results have not been entirely satisfactory because the waste is high, a situation that motivates them to study more deeply the main weaknesses that affect sustainable resource use. Farmer’s participation in the administration of water infrastructure is important, as well as providing financial resources for the conservation of water system; and participation in activities of construction and repaired of water infrastructure. Farmer’s should also plan and design strategies for water conservation. This situation requires an appropriate level of technology and intellectual, rather than local producers and thus no complicated sustainable resource management. That is what local producers don’t have and therefore it complicates the sustainable management of the resource

Analysis of inequality in fertility curves fitted by gamma distributions

The aim of this paper is to analyse fertility curves from a novel viewpoint, that of inequality. Through sufficient conditions that can be easily verified, we compare inequality, in the Lorenz and Generalized Lorenz sense, in fertility curves fitted by gamma distributions, thus achieving a useful complementary instrument for demographic analysis. As a practical application, we examine inequality behaviour in the distributions of specific fertility curves in Spain from 1975 to 2009.Peer Reviewe

Análisis de la secreción de endoglina en exosomas y su relación con el proceso metastásico

El melanoma cutáneo es una neoplasia que se debe al crecimiento y invasión anormal de los melanocitos de la piel, siendo una de las causas de muerte más relevantes entre los cánceres de piel. Datos previos del laboratorio del Dr. Peinado apoyan que los exosomas tumorales (pequeñas vesículas secretadas por el tumor), juegan un papel crucial en la progresión tumoral y metástasis. Datos preliminares obtenidos mediante espectrometría de masas de exosomas tumorales de melanoma demuestran que Endoglina podría ser un nuevo candidato secretado en exosomas e implicado en la colaboración tumor-microambiente.Endoglina tiene un papel muy importante en la angiogénesis y postulamos que su secreción podría contribuir a la comunicación tumor-endotelio. Datos preliminares sugieren que la expresión de endoglina en otros tipos tumorales está relacionada con la expresión de PDGFR-β (PlateletDerivedGrowth Factor Receptor Beta). En este trabajo hemos caracterizado varias líneas celulares de melanoma humano y neurofibromatosis de tipo 1 en la expresión de endoglina y PDGFR-β mediante PCR cuantitativa (qPCR) y Western Blot. Asimismo, hemos silenciado endoglina en la línea celular de melanoma SKMEL28 y se ha analizado la presencia de endoglina en los exosomas aislados de células. Nuestros datos indican que endoglina es un potencial candidato secretado en exosomas de melanoma que podría estar implicado en el proceso metastásic

Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET

El pdf del artículo es el manuscrito de autor.-- et al.Tumor-derived exosomes are emerging mediators of tumorigenesis. We explored the function of melanoma-derived exosomes in the formation of primary tumors and metastases in mice and human subjects. Exosomes from highly metastatic melanomas increased the metastatic behavior of primary tumors by permanently 'educating' bone marrow progenitors through the receptor tyrosine kinase MET. Melanoma-derived exosomes also induced vascular leakiness at pre-metastatic sites and reprogrammed bone marrow progenitors toward a pro-vasculogenic phenotype that was positive for c-Kit, the receptor tyrosine kinase Tie2 and Met. Reducing Met expression in exosomes diminished the pro-metastatic behavior of bone marrow cells. Notably, MET expression was elevated in circulating CD45(-)C-KIT(low/+)TIE2(+) bone marrow progenitors from individuals with metastatic melanoma. RAB1A, RAB5B, RAB7 and RAB27A, regulators of membrane trafficking and exosome formation, were highly expressed in melanoma cells. Rab27A RNA interference decreased exosome production, preventing bone marrow education and reducing, tumor growth and metastasis. In addition, we identified an exosome-specific melanoma signature with prognostic and therapeutic potential comprised of TYRP2, VLA-4, HSP70, an HSP90 isoform and the MET oncoprotein. Our data show that exosome production, transfer and education of bone marrow cells supports tumor growth and metastasis, has prognostic value and offers promise for new therapeutic directions in the metastatic process.Peer Reviewe

Prácticas de Responsabilidad Social Empresarial en las MiPymes del estado de Sinaloa y su impacto ambiental

Día con día, las empresas se enfrentan a mercados cada vez más globalizados y se desenvuelven en un entorno de cambios constantes, en el cual la responsabilidad social empresarial RSE se reconoce como una estrategia de gestión fundamental para que las organizaciones descubran como crear valor para todos sus grupos de interés, mediante un nuevo concepto de creación de valor compartido, buscan el progreso social y económico. El presente trabajo de investigación tiene como objetivo analizar la incorporación de prácticas de RSE a las micros, pequeñas y medianas empresas mipymes en el estado de Sinaloa México y su impacto al medio ambient e Por lo que, se estudi aron las experiencias de em presarios propietarios o directivos de este grupo de empresas certificadas con el distintivo de empresa socialmente responsable ( en los municipios de Mazatlán, Culiacán, Ahome y Guasave del estado de Sinaloa. La investigación se desarrolló como un est udio cualitativo, de tipo exploratorio descriptivo; se aplicaron 37 encuestas y una entrevista semiestructurada dirigidas a gerentes o propietarios de mipymes que han optado por implementar prácticas socialmente responsables y que cuentan con algún tipo de distintivo o certificación como ESR. Los resultados muestran que este universo de empresas ha optado por una cultura empresarial orientada al cuidado del me dio ambiente, aplicando estrategias organizacionales para aminorar las externalidades negativas en los procesos de producción y/o comerciali zación, favoreciendo el bien común al tiempo que buscan con ello ser más competitivas

Characterization of Hydrocarbon-Contaminated Sites Based on Geoelectrical Methods of Geophysical Exploration

Electrical methods are effective tools for the characterization of oil-contaminated sites and are applied in defining the geometry of the contaminated plume and in designing the remedial process. The optimal methodology integrates geoelectric methods, data processing, and interpretation techniques. Electromagnetic profiling is a reliable and fast method used to provide the configuration of oil-contaminated plume from apparent resistivity map and used to guide the subsequent electrical resistivity tomography survey. From advanced field work methods, data processing, and interpretation procedures, electrical resistivity tomography survey provides the three-dimensional (3D) configuration of the contaminated plume, migration pathways, location of active contaminated sources, and information about lithology. For separate contaminated and clean zones, a petrophysical modeling is used for the calculation of soil resistivity based on groundwater salinity. Taking the pore-water salinity value into account, an inversion algorithm recalculates resistivity maps into maps of clay content, porosity, and cation exchange capacity, allowing a more accurate determination of the volume of contaminated soil. From clay content data, hydraulic conductivity values are calculated for determining the groundwater vulnerability due to vertical migration of contaminants from upper layers. The optimal geoelectric methodology is an efficient procedure to assess hydrocarbon-contaminated sites, with emphasis on large sites with deeper groundwater table

Aporte al desarrollo económico y bienestar social de la actividad acuícola camaronera en el municipio Guasave, Sinaloa, México

Las aportaciones del sector acuícola han hecho destacar esta actividad como un promotor de la seguridad alimentaria en el municipio de Guasave, Sinaloa, ya sea por la producción de alimentos, derrama económica y la generación de empleos, sin embargo, al ser una actividad comparativamente nueva, existe un desconocimiento desde una perspectiva administrativa de la productividad tanto interna como social, de las granjas camaroneras del municipio. Las granjas productoras de camarón blanco en el municipio han aportado a la economía familiar y regional ventajas, no obstante, la mayoría de estas no han sido documentadas de forma adecuada que permitan dimensionar ante la sociedad las atribuciones y el crecimiento sostenido de la actividad de las granjas productoras de camarón. El objetivo de esta investigación se enfoca en recolectar información de los actores principales en las actividades acuícolas, tanto personal técnico, que labora en las granjas y del mismo modo, forman parte de familias guasavenses que perciben las principales aportaciones económicas y de bienestar social producto de su trabajo. Mediante una investigación cualitativa, se obtuvo la información entre las granjas, aplicando encuestas al personal que labora en ellas, entrevistas a los órganos administrativos y fuentes de información oficial de las granjas productoras de camarón, con todo esto, se realizó la triangulación de información desde dos perspectivas: una económica y una social. Como resultado, se determinó que, las granjas camaroneras del municipio de Guasave, representan una importante fuente de trabajos (fijos y eventuales), cuyo salario va desde 3.5 a 4.1 veces más que el salario mínimo oficial al año 2017, lo que da lugar a trabajadores satisfechos con salarios competitivos con respecto a otras actividades del sector primario, traduciéndose en bienestar social para el municipio de Guasave. En cuanto a la derrama económica de las granjas productoras de camarón de la región, han mantenido su producción, a pesar de las problemáticas sociales, económicas y sanitarias por lo que se perfila como una de las actividades con un crecimiento sostenido, aunado así a las aportaciones fiscales que genera la camaronicultura, y que ha provocado un aumento de hasta un 300% del Impuesto Predial Rústico. Las contribuciones del sector acuícola, deben considerarse en función a su participación para la generación de políticas públicas, para fortalecer el desarrollo económico y bienestar social de quienes la desarrollan y se benefician de esta actividad y con ello generar infraestructura y conocimiento científico que propicien una mejora en la productividad de las granjas camaroneras

Estimation of Hydrological Parameters from Geoelectrical Measurements

In the coastal aquifer of the lowlands on the right side of the river Sinaloa there is need for fresh water for agricultural development since, around 15% of the water used in agricultural irrigation, is from underground sources. This situation is exacerbated in periods of drought, which promotes drilling with the risk of finding brackish water in them; besides, there is the risk of not meeting water demand due to low hydraulic transmissivity (T) of the aquifer, putting at risk the drilling costs that this implies. In this sense, the determination of T and K (hydraulic conductivity) is important for the development and management of groundwater exploitation of the study area. Generally by means of pumping tests in wells, T is obtained, with high costs, so there are few values of T. K is generally obtained by wells and laboratory test. The aim of this chapter is to establish an empirical relationship between T and K with Dar-Zarrouk parameter in porous media, transverse resistance (T R ), in addition to a characterization of the water quality through the electrical resistivity. This parameter is estimated from surface resistivity measurements, which are more economical in relation to the pumping tests; thus, T was characterized in the study area. The coefficient of correlation of the exponential adjustment is 0.79 and the relation is T=137185.7 TR0.020758−156691 and K=367.210.0548−518.813 with coefficient of correlation of 0.678

The transcription factor Slug represses E-cadherin expression and induces epithelial to mesenchymal transitions: a comparison with Snail and E47 repressors

13 pages, 7 figures.Transcriptional repression mechanisms have emerged as one of the crucial processes for the downregulation of E-cadherin expression during development and tumour progression. Recently, several E-cadherin transcriptional repressors have been characterized (Snail, E12/E47, ZEB-1 and SIP-1) and shown to act through an interaction with proximal E-boxes of the E-cadherin promoter. We have analyzed the participation of another member of the Snail family, Slug, and observed that it also behaves as a repressor of E-cadherin expression. Stable expression of Slug in MDCK cells leads to the full repression of E-cadherin at transcriptional level and triggers a complete epithelial to mesenchymal transition. Slug-induced repression of E-cadherin is mediated by its binding to proximal E-boxes, particularly to the E-pal element of the mouse promoter. Detailed analysis of the binding affinity of different repressors to the E-pal element indicates that Slug binds with lower affinity than Snail and E47 proteins. These results, together with the known expression patterns of these factors in embryonic development and carcinoma cell lines, support the idea that the in vivo action of the different factors in E-cadherin repression can be modulated by their relative concentrations as well as by specific cellular or tumour contexts.This work was supported by the Spanish Ministry of Science and Technology (SAF2001-2819), Instituto de Salud Carlos III (FIS01/1174) and the Comunidad Autónoma de Madrid (08.1/0055./2000). V.B. has been funded by predoctoral fellowships from the Fundación Científica de la Asociación Española contra el Cáncer (AECC) and Instituto de Salud Carlos III. H.P. is a predoctoral fellow of the Spanish Ministry of Education, Culture and Sports.Peer reviewe