An analysis of geographical concentration of productivity: the case of manufacture firms in the Ebro Valley

En este trabajo se analiza la concentración espacial de las empresas de manufacturas ubicadas en el Valle del Ebro, atendiendo a sus niveles de productividad. El periodo que utilizamos es 1996 a 2009. Los resultados obtenidos nos permiten valorar el impacto del entorno socioeconómico y geográfico del Valle del Ebro en la tendencia a la concentración de la productividad, lo que se conoce como externalidades espaciales. Estos resultados muestran una fuerte correlación entre tamaño del municipio, densidad y productividad. A nivel provincial, destacan las concentraciones de alta productividad en Barcelona, La Rioja, Girona y Navarra. Otros factores que ejercen un efecto positivo sobre la concentración de la productividad son: i) el atractivo del emplazamiento con preferencia por la litoralidad; ii) la cercanía a infraestructuras de comunicaciones como la autopista A2; iii) la diversidad de empresas entendida como existencia, en el entorno de una empresa, de otras empresas de sectores complementarios. Entre los aspectos que influyen negativamente sobre los datos de productividad destacan las dificultades de comunicación con el exterior, la falta de presión demográfica y la desventaja tecnológica.In this work we analyse the spatial concentration of manufacture firms in the Ebro Valley, in relation to their productivity level. We use data for the period 1996 to 2009. The results allow to evaluate the impact of socio-economic and geographic aspects of the Ebro Valley on productivity concentration, known as spatial externalities. Results show a positive strong correlation among size of municipality, density and productivity. Among provinces, it is remarkable the high concentration of productivity in Barcelona, La Rioja, Girona and Navarra. Other factors with a positive effect on productivity concentration are the following: i) the environment attractiveness, with a strong preference for the coast; ii) the accessibility to communication infrastructures such as the A2 highway; iii) diversity, understood as the existence, in the proximity, of other firms belonging to different and complementary activity sectors. Factors that negatively affect the concentration of productivity are accessibility difficulties, low demographic pressure and technological disadvantages.Fil: Angulo, Ana M.. Universidad de Zaragoza; España;Fil: Herrera Gomez, Marcos Hernan. Universidad Nacional de Salta. Facultad de Ciencias Económicas, Jurídicas y Sociales. Instituto de Estudios Laborales y del Desarrollo Económico; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Salta; ArgentinaFil: Atwi , Majed. Universidad de Zaragoza; España

BASIS FOR TARGETING MET ACTIVATION MEDIATED RESISTANCE TO PI3K INHIBITION IN BREAST CANCER

The identification of resistance mechanisms to emerging therapies, such as those targeting the PI3K pathway and the MET receptor, has the potential to benefit a significant number of patients with breast cancer. In this study we hypothesized that concurrent aberrations in PI3K and MET will render breast cancers resistant to therapies targeting each pathway, and that combination therapy targeting the PI3K and MET pathway will optimize therapy-effect by preventing the acquisition of resistance. We analyzed cMET and phospho-cMET levels in 257 breast cancer samples and found that high levels of both the proteins were seen in all breast cancer subtypes, which correlated with poor prognosis.(1) We also analyzed DNA from 971 FFPE early breast tumors, and showed that MET and PIK3CA are frequently co-amplified, and a high copy number of either gene is associated with poorer prognostic features and the triple negative disease.(2) Additionally, we determined the effect of MET-T1010I, MET-Y1253D and MET overexpression, found in breast cancers, on the activity of the two most common breast cancer PIK3CA mutations (E545K and H1047R), in a model of breast epithelial cells (MCF-10A) and a cell line breast cancer model (HCC1954). Our results suggest that tumors with concurrent aberrations in MET and PIK3CA are likely to be more aggressive and resistant to therapies targeting each pathway, and that combinatorial therapy (with MET and PI3K pathway inhibitors) could circumvent this resistance. This is the first study to investigate the significance of differential expression of cMET and p-cMET in different breast cancer subtypes, to report p-cMET levels as a prognostic factor in breast cancer, and also, the first to report MET gene copy number, its distribution by tumor subtype, and correlation with patient outcome.(2) Our study is also unique for showing that the presence of MET aberrations enhances the tumorigenic effects induced by the PIK3CA mutations in breast cancer/epithelial cells; results from our tumor xenograft models corroborate with these in vitro findings. Moreover, we are the first to provide evidence for the potential activity of combinatorial therapy using MET and PI3K pathway inhibitors against breast cancer

Efectos de varios factores ambientales sobre las tasas de descomposición en encinares mediterráneos

Resumen de una presentación realizada en: I Simposio sobre Interacciones Planta-Suelo (ICA-CSIC, Madrid, 25-26 Febrero 2016)[ES] Los encinares son ecosistemas de gran valor que están sufriendo un proceso de decaimiento, lo que puede afectar a su capacidad para almacenar carbono. Se plantea este proyecto de tesis para estudiar el efecto del decaimiento de encinares sobre las tasas de descomposición de la hojarasca, las raíces y las herbáceas, y los factores medioambientales que la controlan. Los factores que se pretende estudiar son: la calidad de la materia en descomposición, el clima, la fotodegradación, y el efecto de diferentes conjuntos de fauna del suelo. El efecto de dichos factores sobre la descomposición se analizará a través de 4 experimentos con bolsas de descomposición. Experimento 1: Efecto del clima, de la fotodegradación y de la calidad de la hojarasca sobre las tasas de descomposición. Se ha diseñado un experimento factorial para el seguimiento de las tasas de descomposición de herbáceas y de hojas y raíces de encinas, situando bolsas en 8 encinares afectados distribuidos por el territorio peninsular español. Experimento 2: Efecto de la microfauna, la mesofauna y la macrofauna del suelo sobre los procesos de descomposición de hojarasca. Se estudiará mediante tratamientos de exclusión de fauna del suelo. Experimento 3: Efecto interactivo de la temperatura, precipitación y radiación solar sobre la descomposición de hojarasca. Se utilizarán mesocosmos para someter bolsas de hojarasca de herbáceas a dos niveles para cada uno de esos tres factores, con todas las interacciones entre ellos. Experimento 4: Contribución de diferentes procesos abióticos (fotodegradación y degradación térmica), bióticos (descomposición microbiana) así como su interacción en la descomposición de la materia orgánica. Se realizará con herbáceas bajo condiciones controladas de laboratorio. Estos experimentos permitirán describir de una manera mecanicista un proceso tan relevante para las interacciones planta-suelo como es la descomposición así como los factores medioambientales que la controlan.Peer reviewe

Relación entre la calidad de vida en salud y la carga física en cuidadores de personas con enfermedad de Alzheimer.

Caregivers of chronic patients are themselves potential patients, who perceive a major impact on health because of their role in the care of another individual. Objective: To describe the relationship between the quality of life in health and the physical burden in caregivers of people with Alzheimer’s disease. Methodology: A documentary review was conducted with a qualitative approach and non-experimental design, taking into account different texts such as theses, articles, blogs And news, among others, the technique of content analysis was applied. Results: It was found that the quality of life of caregivers’ health is clearly affected by the physical efforts they make in their caregiving, according to the amount of time invested and the stage of the pathology of the person with Alzheimer’s disease, as it progresses Pathology, increases physical dependence. The caregiver is limited only to perform activities on which the patient depends, neglecting his own health. Osteomuscular disorders and associated pains, cardiovascular pathologies, gastrointestinal disorders, disorders of the immune system, respiratory problems, tension headache, insomnia, daytime hypersomnia, nightmares, anemia, skin infections, decreased physical capacity, clumsy movement, less agile and unsafe, Feeling of dissatisfaction, feeling tired and exhausted. Conclusion: Caregivers have an inadequate quality of life and that at some point the consequences for them can be devastating.Los cuidadores de enfermos crónicos son en sí mismo enfermos potenciales, que perciben un gran impacto en la salud a causa de su rol en a atención de otro individuo. Objetivo: Describir la relación entre la calidad de vida en salud y la carga física en cuidadores de personas con enfermedad de Alzheimer Métodología: Se realizó una revisión documental con enfoque cualitativo y diseño no experimental, se tuvo en cuenta diferentes textos como tesis, artículos, blogs y noticias, entre otros, se aplicó la técnica de análisis de contenido. Resultados: Se encontró que la calidad de vida en salud de los cuidadores se ve claramente afectada por los esfuerzos físicos que realizan en su labor de cuidar, según la cantidad de tiempo invertido y el estadio de la patología de la persona con Alzheimer, a medida que avanza la patología, aumenta la dependencia física. El cuidador se ve limitado únicamente a realizar actividades de las que depende el enfermo, descuidando la propia salud. Se encontró trastornos osteomusculares y dolores asociados, patologías cardiovasculares, trastornos gastrointestinales, alteraciones del sistema inmunológico, problemas respiratorios, cefalea tensional, insomnio, hipersomnia diurna, pesadillas, anemia, infecciones cutáneas, disminución de la capacidad física, movimiento torpes, menos agiles e inseguros, sensación de insatisfacción, sensación de cansancio y agotamiento. Conclusión: Los cuidadores tienen una inadecuada calidad de vida y que en algún momentos las consecuencias para los mismo pueden ser devastadoras

Anatomía foliar de especies predominantes en bosques y pastizales del Iberá

The Iberá macrosystem has several types of vegetation, where in addition to aquatic and marsh vegetation are found hydrophilic forests, savannahs with a predominance of grasses and grasslands with shrub species interspersed among the herbaceous species. Previous studies of leaf anatomy were only carried out on aquatic and marsh plants. In this work, leaf anatomy was studied in predominant or frequent species growing in grasslands and forests of the Iberá macrosystem, with the aim of detecting leaf structural characters that may represent adaptive value to these environments. Leaves of 42 species corresponding to 26 families were analyzed with optical and scanning electron microscopy. Statistical analysis was performed based on a data matrix of the anatomical characters analyzed, also including the environment types in which the species studied grow. The analyzed characters of the epidermis were: cuticle design, stomata, trichomes, design of epidermal cells of both epidermis, where a predominance of identical morphology on both sides was observed. In the mesophyll, the type, presence and form of calcium and inulin crystals, and distribution of glandular structures such as laticifers, cavities and secretory cells were evaluated. The data reported are discussed in relation to the available literature. No constant characters associated with a particular vegetation type are found. Species living in the same environment do not have similar anatomical features, as shown by clustering analysis (UPGMA).El macrosistema Iberá presenta diversos tipos de vegetación, donde además de las acuáticas y palustres hay bosques hidrófilos, sabanas con predominio de gramíneas y praderas con especies arbustivas intercaladas entre las herbáceas. Estudios previos de anatomía foliar solo fueron realizados en plantas acuáticas y palustres. En este trabajo se estudió la anatomía foliar en especies predominantes o frecuentes que crecen en pastizales y bosques del macrosistema Iberá, con el objetivo de detectar caracteres estructurales de las hojas que puedan representar valor adaptativo a estos ambientes. Se analizaron hojas de 42 especies correspondientes a 26 familias, con microscopía óptica y electrónica de barrido. Se realizó un análisis estadístico en base a una matriz de datos, compuesta por los caracteres anatómicos y el ambiente en que crecen las especies estudiadas. Los caracteres analizados de la epidermis fueron: diseño de la cutícula, estomas, tricomas, diseño de células epidérmicas de ambas epidermis, donde se observa un predominio de idéntica morfología en ambas caras. En el mesofilo se evaluó su tipo, presencia y forma de cristales de calcio e inulina, y distribución de estructuras glandulares como laticíferos, cavidades y células secretoras. Los datos reportados son discutidos en relación a la bibliografía disponible. El análisis de agrupamiento (UPGMA) muestra que las especies que habitan en los mismos ambientes no presentan características anatómicas similares

Functional consequence of the MET-T1010I polymorphism in breast cancer.

Major breast cancer predisposition genes, only account for approximately 30% of high-risk breast cancer families and only explain 15% of breast cancer familial relative risk. The HGF growth factor receptor MET is potentially functionally altered due to an uncommon germline single nucleotide polymorphism (SNP), MET-T1010I, in many cancer lineages including breast cancer where the MET-T1010I SNP is present in 2% of patients with metastatic breast cancer. Expression of MET-T1010I in the context of mammary epithelium increases colony formation, cell migration and invasion in-vitro and tumor growth and invasion in-vivo. A selective effect of MET-T1010I as compared to wild type MET on cell invasion both in-vitro and in-vivo suggests that the MET-T1010I SNP may alter tumor pathophysiology and should be considered as a potential biomarker when implementing MET targeted clinical trials

PI3K Pathway Mutations and PTEN Levels in Primary and Metastatic Breast Cancer

The purpose of this work was to determine whether there are differences in PIK3CA mutation status and PTEN protein expression between primary and matched metastatic breast tumors as this could influence patient management. Fifty-micron paraffin sections were used for DNA extraction and 3-micron slides for immunohistochemistry (IHC) and fluorescent in-situ hybridization (FISH). ER, PR and HER2 IHC were repeated in a central laboratory for both primary and metastasis. PTEN levels were assessed by IHC and PI3K pathway mutations detected by a mass spectroscopy-based approach. Median age was 48 years (range, 30 to 83 years). Tumor subtype included 72% hormone receptor-positive/HER2-negative, 20% HER2-positive, and less than 7.8% triple receptor negative. Tissues were available for PTEN IHC in 46 primary tumors and 52 metastases. PTEN was lost in 14 (30%) primary tumors and 13 (25%) metastases. There were 5 cases of PTEN loss and eight cases of PTEN gain from primary to metastasis (26% discordance). Adequate DNA was obtained on 46 primary tumors and on 50 metastases for PIK3CA analysis. PIK3CA mutations were detected in 19 (40%) of primary tumors and 21 (42%) of metastases. There were five cases of PIK3CA mutation loss, and four cases of mutation gain (18% discordance). There was an increase of the level of PIK3CA mutations in four cases, and decrease in one from primary to metastasis. There is a high level of discordance in PTEN level, PIK3CA mutations, and receptor status between primary and metastatic disease that may influence patient selection and response to PI3K-targeted therapies

Decreased and Heterogeneous Neutralizing Antibody Responses Against RBD of SARS-CoV-2 Variants After mRNA Vaccination.

The rapid spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) emerging variants raises concerns about their capacity to evade immune protection provided by natural infection or vaccination. The receptor-binding domain (RBD) of the viral spike protein is the major target of neutralizing antibodies, and viral variants accumulate mutations in this region. In this study, we determined the antibody neutralization capacity against the RBD of SARS-CoV-2 variants Alpha (B.1.1.7), Gamma (P.1), Epsilon (B.1.427), Kappa (B.1.617.1), and Delta (B.1.617.2) in a cohort of healthcare workers naturally infected or receiving COVID-19 mRNA vaccines from Moderna or Pfizer-BioNTech. We show that the five RBD variants displayed an augmented binding to ACE2 compared to the original Wuhan strain. The most significant increase was observed in variants Epsilon and Delta, containing mutation L452R. Using a flow cytometry cell-based assay, we found that SARS-CoV-2-infected subjects presented low levels of RBD-specific neutralizing antibodies against all variants analyzed, except Alpha. However, the neutralizing activity incremented considerably after a subsequent mRNA-vaccine dose, to levels significantly higher than those in naïve individuals receiving two vaccine doses. Importantly, we observed partially impaired neutralizing responses against most variants in fully vaccinated individuals. Variants Gamma and Kappa encompassing RBD E484K/Q mutations presented the highest neutralizing resistance. Furthermore, a wide heterogeneity in the magnitude of RBD-specific neutralizing responses against all tested SARS-CoV-2 variants following both mRNA vaccines was detected. Altogether, our findings provide important knowledge regarding SARS-CoV-2 vaccine-induced immunity, and should be very useful to guide future vaccination regimens and personalized vaccine approaches