Therapeutic targeting of HER2–CB2R heteromers in HER2-positive breast cancer

There is a subtype of breast cancer characterized by the overexpression of the oncogene HER2. Although most patients with this diagnosis benefit from HER2-targeted treatments, some do not respond to these therapies and others develop resistance with time. New tools are therefore warranted for the treatment of this patient population, and for early identification of those individuals at a higher risk of developing innate or acquired resistance to current treatments. Here, we show that HER2 forms heteromer complexes with the cannabinoid receptor CB2R, the expression of these structures correlates with poor patient prognosis, and their disruption promotes antitumor responses. Collectively, our results support HER2–CB2R heteromers as new therapeutic targets and prognostic tools in HER2+ breast cancer

Association of a single nucleotide polymorphism combination pattern of the Klotho gene with non-cardiovascular death in patients with chronic kidney disease

Chronic kidney disease (CKD) is associated with an elevated risk of all-cause mortality, with cardiovascular death being extensively investigated. However, non-cardiovascular mortality represents the biggest percentage, showing an evident increase in recent years. Klotho is a gene highly expressed in the kidney, with a clear influence on lifespan. Low levels of Klotho have been linked to CKD progression and adverse outcomes. Single nucleotide polymorphisms (SNPs) of the Klotho gene have been associated with several diseases, but studies investigating the association of Klotho SNPs with noncardiovascular death in CKD populations are lacking. The main aim of this study was to assess whether 11 Klotho SNPs were associated with non-cardiovascular death in a subpopulation of the National Observatory of Atherosclerosis in Nephrology (NEFRONA) study (n ¼ 2185 CKD patients). After 48 months of follow-up, 62 cardiovascular deaths and 108 non-cardiovascular deaths were recorded. We identified a high non-cardiovascular death risk combination of SNPs corresponding to individuals carrying the most frequent allele (G) at rs562020, the rare allele (C) at rs2283368 and homozygotes for the rare allele (G) at rs2320762 (rs562020 GG/AG þ rs2283368 CC/CT þ rs2320762 GG). Among the patients with the three SNPs genotyped (n ¼ 1016), 75 (7.4%) showed this combination. Furthermore, 95 (9.3%) patients showed a low-risk combination carrying all the opposite genotypes (rs562020 AA þ rs2283368 TT þ rs2320762 GT/TT). All the other combinations [n ¼ 846 (83.3%)] were considered as normal risk. Using competing risk regression analysis, we confirmed that the proposed combinations are independently associated with a higher fhazard ratio [HR] 3.28 [confidence interval (CI) 1.51-7.12]g and lower [HR 6 × 10- (95% CI 3.3 × 10--1.1 × 10-)] risk of suffering a non-cardiovascular death in the CKD population of the NEFRONA cohort compared with patients with the normal-risk combination. Determination of three SNPs of the Klotho gene could help in the prediction of non-cardiovascular death in CKD

Servicios ecosistémicos como soporte para la gestión de sistemas socioecológicos: aplicación en agroecosistemas

With the purpose to answer question the new interdisciplinary approaches to ecosystem services and socio-ecological systems are relevant for the sustainable management of both natural systems as agroecosystem?, A review of the evolving concepts of ecosystem services and socio-ecological systems is made, and thematic developments with critical analysis in greater detail in studies on agro made in Colombia. Disputes and differential approaches are examined from ecology and economics to synthesize in delimiting three core to develop work with local emphasis: understanding and managing uncertainty and methods to identify, qualify and quantify ecosystem services and their relationship with biodiversity (trades - offs, dis- service, synergies) and the particular analysis and adjusted to the context of cultural ecosystem services.A fim de responder à pergunta as novas abordagens interdisciplinares de serviços ecossistemicos e de sistemas sócioecológicos são relevantes para a gestão sustentável de ambos os sistemas naturais e agrossistemas?, se faz avaliação da evolução dos conceitos serviços ecossistêmicos é sistemas socio ecologicos, dos avancos tematicos com análise crítica, e em maior detalhe nos estudos sobre agro ecossistemas feitos na Colômbia. Se discute abordagens diferenciais de ecologia e economia para sintetizar na delimitação de três eixos centrais para desenvolver trabalhos com ênfase nas áreas locais de compreensão e manejo da incerteza, os métodos para identificar, qualificar e quantificar os serviços dos ecossistemas e suas relações biodiversidade (comércios-offs, sinergias, dis-service) e a análise especial e adaptadas ao contexto dos serviços ecossistemicos culturais.Con el propósito de responder a la pregunta ¿los nuevos enfoques interdisciplinares de servicios ecosistémicos y de sistemas socioecológicos son pertinentes para la gestión sostenible tanto de sistemas naturales como de agroecosistemas?, se hace una revisión de la evolución de los conceptos servicios ecosistémicos y sistemas socioecológicos, de los avances temáticos con análisis crítico, y con mayor detalle en los estudios sobre agroecosistemas realizados en Colombia. Se examinan controversias y enfoques diferenciales desde la ecología y economía para sintetizar en la delimitación de tres ejes centrales a desarrollar en trabajos con énfasis local: la comprensión y manejo de la incertidumbre, los métodos para identificar, cualificar y cuantificar los servicios ecosistémicos y sus relaciones con la biodiversidad (trades-offs, dis-servicios, sinergias) y el análisis particular y ajustado al contexto de los servicios ecosistémicos culturales

Ecosystem Services as support for the Management of socioecological systems: application in agroecosystems

Con el propósito de responder a la pregunta ¿los nuevos enfoques interdisciplinares de servicios ecosistémicos y de sistemas socioecológicos son pertinentes para la gestión sostenible tanto de sistemas naturales como de agroecosistemas?, se hace una revisión de la evolución de los conceptos servicios ecosistémicos y sistemas socioecológicos, de los avances temáticos con análisis crítico, y con mayor detalle en los estudios sobre agroecosistemas realizados en Colombia. Se examinan controversias y enfoques diferenciales desde la ecología y economía para sintetizar en la delimitación de tres ejes centrales a desarrollar en trabajos con énfasis local: la comprensión y manejo de la incertidumbre, los métodos para identificar, cualificar y cuantificar los servicios ecosistémicos y sus relaciones con la biodiversidad (trades-offs, dis-servicios, sinergias) y el análisis particular y ajustado al contexto de los servicios ecosistémicos culturales.Palabras clave: biodiversidad; Orinoquia; altillanura; compensaciones; gestión ambiental; sostenibilidadWith the purpose to answer question the new interdisciplinary approaches to ecosystem services and socio-ecological systems are relevant for the sustainable management of both natural systems as agroecosystem?, A review of the evolving concepts of ecosystem services and socio-ecological systems is made, and thematic developments with critical analysis in greater detail in studies on agro made in Colombia. Disputes and differential approaches are examined from ecology and economics to synthesize in delimiting three core to develop work with local emphasis: understanding and managing uncertainty and methods to identify, qualify and quantify ecosystem services and their relationship with biodiversity (trades - offs, dis- service, synergies) and the particular analysis and adjusted to the context of cultural ecosystem services.Key words: biodiversity; Orinoco; highthills; trades-off; environmental management; sustainabilit

Distribution of tilapia, Oreochromis mossambicus (Perciformes: Cichlidae), and water body characíeristics in Quintana Roo, Mexico

Based on field colIection in freshwater bodies (1992 to 1996) in the Mexican State of Quintana Roo, Yucatan Península, as well ason official reports from the former Mexican Ministry of Fisheries, this work documents the distribution of tilapia in the state, and its relative abundance as a function of water body afea. Introductions oí" tiJapia in Quintana Roo began in 1974; !hese were mainly extensíve 'cultures (direct releases) until 1982, when floating cages began to be used. The fish were coIlected with throw, seine, and hand nets, plastic bags OI hook and line, as !he local conditions allowed; each fishing gear provided a separate abundance estímate for a given site. Water body area was calculated from maps (1:50 OOO) by clipping the lake area in homogeneously !hick paper and weighing it to !he neares! 0.1 mg. Temperature, conductivity and dissolved oxygen, as well as the number of native fish species, were recorded, but these variables showed no relationship to tilapia abundance or distribution; however, tilapia was not found in the wild at water conductivities aboye 5500 mmho/cm. Escape from floating cages, perhaps caused by crocodiles or water level elevations, was found in 50% of the intensive culture sites visited. Moreover, tilápia (Oreochromis mossambicus and hybrids, probably with O. niloticus) was captured in four sites where it had not been officially introduced; two of these maybe natural invasions from nearby lakes during wetter cyc1es, the others (lakes Cobá and Makanxoc) probably are unofficial introductions. Tilapia was not frequent throughout Quintana Roo (4.2% of 237 water bodies visited), but it was dominant (>20% of !he total number of individuals) in most localities where it appeared, inc1uding lake Chichancanab, habitat of an endemic Cyprinodon species flock. The correlation between the logaritbm of water body area and tilapia re1ative abundance was significantly negative, possibly meaning that smaller sites were more vulnerable to tílapia proliferatíon.Based on field colIection in freshwater bodies (1992 to 1996) in the Mexican State of Quintana Roo, Yucatan Península, as well ason official reports from the former Mexican Ministry of Fisheries, this work documents the distribution of tilapia in the state, and its relative abundance as a function of water body afea. Introductions oí" tiJapia in Quintana Roo began in 1974; !hese were mainly extensíve 'cultures (direct releases) until 1982, when floating cages began to be used. The fish were coIlected with throw, seine, and hand nets, plastic bags OI hook and line, as !he local conditions allowed; each fishing gear provided a separate abundance estímate for a given site. Water body area was calculated from maps (1:50 OOO) by clipping the lake area in homogeneously !hick paper and weighing it to !he neares! 0.1 mg. Temperature, conductivity and dissolved oxygen, as well as the number of native fish species, were recorded, but these variables showed no relationship to tilapia abundance or distribution; however, tilapia was not found in the wild at water conductivities aboye 5500 mmho/cm. Escape from floating cages, perhaps caused by crocodiles or water level elevations, was found in 50% of the intensive culture sites visited. Moreover, tilápia (Oreochromis mossambicus and hybrids, probably with O. niloticus) was captured in four sites where it had not been officially introduced; two of these maybe natural invasions from nearby lakes during wetter cyc1es, the others (lakes Cobá and Makanxoc) probably are unofficial introductions. Tilapia was not frequent throughout Quintana Roo (4.2% of 237 water bodies visited), but it was dominant (>20% of !he total number of individuals) in most localities where it appeared, inc1uding lake Chichancanab, habitat of an endemic Cyprinodon species flock. The correlation between the logaritbm of water body area and tilapia re1ative abundance was significantly negative, possibly meaning that smaller sites were more vulnerable to tílapia proliferatíon

La cuenca del río Orotoy: conocimientos para la gestión teritorial

La investigación en adaptación a los cambios globales de la sociedad y de la biodiversidad se ha desarrollado principalmente desde dos enfoques: resiliencia y vulnerabilidad. Ambas aproximaciones parecen ser conflictivas y con desarrollos teóricos y metodológicos independientes. A partir de los aprendizajes generados en proyecto “Fortalecimiento de capacidades de adaptación social y ecológica al cambio climático en comunidades de la cuenca del río Orotoy”, se propone un esquema de articulación de estos dos enfoques conceptuales para abordar la gestión integral de la biodiversidad frente al cambio global en la práctica, usando como base el análisis de servicios ecositémicos y la gestión territorial. La primera vía de gestión territorial es aquella en la cual se parte de la información existente sobre los impactos posibles de cada motor de transformación y pérdida sobre la biodiversidad, con miras a identificar cuáles son los efectos potenciales que cada uno de estos puede tener sobre los ecosistemas, los servicios ecosistémicos y las decisiones de gestión. Un segundo enfoque surge de la construcción de resiliencia socioecológica. Para ello, se asume que el reto de la sociedad es asegurar el bienestar humano de cara a los cambios ambientales, sociales y culturales, rápidos y descontrolados, teniendo en cuenta las incertidumbres inherentes que los mismos generan. Desde este enfoque, en la gestión territorial se prioriza el fortalecimiento de capacidades de un sistema socio ecológico para continuar suministrando un conjunto de servicios ecosistémicos deseados en escenarios plausibles. Así, la gestión de la biodiversidad se convierte en una oportunidad para dirigir la transformación del territorio hacia paisajes sostenibles, que suplan de forma óptima los servicios ecosistémicos prioritarios para generar un bienestar integral a la población

Surface-enhanced stereoselectivity in Mukaiyama aldol reactions catalyzed by clay-supported bis(oxazoline)-copper complexes

Surface effects on a laponite-exchanged bis(oxazoline)-copper complex modify the stereochemical course of the Mukaiyama aldol reaction between 2-(trimethylsilyloxy)furan and α-ketoesters, leading up to 90% ee (dr 86: 14) becoming the best overall result obtained for this reaction and significantly improving the homogeneous process. © The Royal Society of Chemistry.This work was made possible thanks to the generous financial support of C.I.C.Y.T. (project CTQ2005-08016 and Consolider Ingenio 2010 CSD2006-0003 and CSD2006-0015) and the Diputación General de Aragón.Peer Reviewe