Caveolin-1 Modulates Mechanotransduction Responses to Substrate Stiffness through Actin-Dependent Control of YAP

The transcriptional regulator YAP orchestrates many cellular functions, including tissue homeostasis, organ growth control, and tumorigenesis. Mechanical stimuli are a key input to YAP activity, but the mechanisms controlling this regulation remain largely uncharacterized. We show that CAV1 positively modulates the YAP mechanoresponse to substrate stiffness through actin-cytoskeleton-dependent and Hippo-kinase-independent mechanisms. RHO activity is necessary, but not sufficient, for CAV1-dependent mechanoregulation of YAP activity. Systematic quantitative interactomic studies and image-based small interfering RNA (siRNA) screens provide evidence that this actin-dependent regulation is determined by YAP interaction with the 14-3-3 protein YWHAH. Constitutive YAP activation rescued phenotypes associated with CAV1 loss, including defective extracellular matrix (ECM) remodeling. CAV1-mediated control of YAP activity was validated in vivo in a model of pancreatitis-driven acinar-to-ductal metaplasia. We propose that this CAV1-YAP mechanotransduction system controls a significant share of cell programs linked to these two pivotal regulators, with potentially broad physiological and pathological implications. Moreno-Vicente et al. report that CAV1, a key component of PM mechanosensing caveolae, mediates adaptation to ECM rigidity by modulating YAP activity through the control of actin dynamics and phosphorylation-dependent interaction of YAP with the 14-3-3-domain protein YWHAH. Cav1-dependent YAP regulation drives two pathophysiological processes: ECM remodeling and pancreatic ADM. © 2018 The Author

Spatial Bayesian Modeling Applied to the Surveys of Xylella fastidiosa in Alicante (Spain) and Apulia (Italy)

The plant-pathogenic bacterium Xylella fastidiosa was first reported in Europe in 2013, in the province of Lecce, Italy, where extensive areas were affected by the olive quick decline syndrome, caused by the subsp. pauca. In Alicante, Spain, almond leaf scorch, caused by X. fastidiosa subsp. multiplex, was detected in 2017. The effects of climatic and spatial factors on the geographic distribution of X. fastidiosa in these two infested regions in Europe were studied. The presence/absence data of X. fastidiosa in the official surveys were analyzed using Bayesian hierarchical models through the integrated nested Laplace approximation (INLA) methodology. Climatic covariates were obtained from the WorldClim v.2 database. A categorical variable was also included according to Purcell’s minimum winter temperature thresholds for the risk of occurrence of Pierce’s disease of grapevine, caused by X. fastidiosa subsp. fastidiosa. In Alicante, data were presented aggregated on a 1 km grid (lattice data), where the spatial effect was included in the model through a conditional autoregressive structure. In Lecce, data were observed at continuous locations occurring within a defined spatial domain (geostatistical data). Therefore, the spatial effect was included via the stochastic partial differential equation approach. In Alicante, the pathogen was detected in all four of Purcell’s categories, illustrating the environmental plasticity of the subsp. multiplex. Here, none of the climatic covariates were retained in the selected model. Only two of Purcell’s categories were represented in Lecce. The mean diurnal range (bio2) and the mean temperature of the wettest quarter (bio8) were retained in the selected model, with a negative relationship with the presence of the pathogen. However, this may be due to the heterogeneous sampling distribution having a confounding effect with the climatic covariates. In both regions, the spatial structure had a strong influence on the models, but not the climatic covariates. Therefore, pathogen distribution was largely defined by the spatial relationship between geographic locations

Criteria for efficient prevention of dissemination and successful eradication of Erwinia amylovora (the cause of fire blight) in Aragon, Spain

Erwinia amylovora was detected on pome fruits in the Aragon region (North-Eastern Spain), in a ca. 5 km radius area located in the mid Jalon river (mid Ebro Valley) in the province of Zaragoza, during 2000-2003. Eight years have now passed since this pathogen was last detected, without new infections being reported in the same area. The bases for surveys and rapid eradication performed have been analyzed in detail to understand the reasons for the success in removing fireblight. The results demonstrate that intensive surveillance, risk assessment, plant analyses using accurate identification methods, and, especially, rapid total or selective eradication of infected trees in the plots have been very effective in preventing the generalized spread of fireblight and in delaying economic losses associated with this disease. Eradication and compensation to growers, estimated to cost approx. (sic) 467,000, were clearly counterbalanced by the economic value of apple and pear production in the 2000-2003 period (approx. (sic) 368 million). Fire blight risk-assessment, using the MARYBLYT system, showed that climatic conditions in the studied area were favourable to infections during the analyzed period (1997-2006). Molecular characterization of E. amylovora strains had revealed their homogeneity, suggesting that these fire blight episodes could have been caused by just one inoculum source, supporting the hypothesis that there was a unique introduction of E. amylovora in the studied area. Spatial spread of E. amylovora to trees was analyzed within six orchards, indicating an aggregated distribution model. This Spanish experience demonstrates the success of scientifically-based prevention methods that lead to the deployment of a fast and strict containment strategy, useful for other Mediterranean areas

Criteria for efficient prevention of dissemination and successful eradication of Erwinia amylovora (the cause of fire blight) in Aragon, Spain

Erwinia amylovora was detected on pome fruits in the Aragon region (North-Eastern Spain), in a ca. 5 km radius area located in the mid Jalon river (mid Ebro Valley) in the province of Zaragoza, during 2000-2003. Eight years have now passed since this pathogen was last detected, without new infections being reported in the same area. The bases for surveys and rapid eradication performed have been analyzed in detail to understand the reasons for the success in removing fireblight. The results demonstrate that intensive surveillance, risk assessment, plant analyses using accurate identification methods, and, especially, rapid total or selective eradication of infected trees in the plots have been very effective in preventing the generalized spread of fireblight and in delaying economic losses associated with this disease. Eradication and compensation to growers, estimated to cost approx. (sic) 467,000, were clearly counterbalanced by the economic value of apple and pear production in the 2000-2003 period (approx. (sic) 368 million). Fire blight risk-assessment, using the MARYBLYT system, showed that climatic conditions in the studied area were favourable to infections during the analyzed period (1997-2006). Molecular characterization of E. amylovora strains had revealed their homogeneity, suggesting that these fire blight episodes could have been caused by just one inoculum source, supporting the hypothesis that there was a unique introduction of E. amylovora in the studied area. Spatial spread of E. amylovora to trees was analyzed within six orchards, indicating an aggregated distribution model. This Spanish experience demonstrates the success of scientifically-based prevention methods that lead to the deployment of a fast and strict containment strategy, useful for other Mediterranean areas

L'Encefalopatia Espongiforme Bovina a Galícia

Galícia ha estat una de les zones d'Espanya on l'Encefalopatia Espongiforme Bovina (EEB) ha tingut més incidència. Va ser a Galícia on es va donar el primer cas d'una vaca afectada per aquesta malaltia, l'any 2000. Un investigador del CRESA ha analitzat la distribució geogràfica dels casos d'EEB i del risc d'infecció a aquesta comunitat autònoma.Galicia is one of the Spanish regions where the Bovine Spongiforme Encephalopathy (BSE) has more impact. The first case of a cow with BSE took place in 2000 in Galicia. Now, a group of researchers has analysed the geographic distribution of BSE cases and the infection risk in this Spanish autonomous community

Identifying the best fishing-suitable areas under the new European discard ban

The spatial management of fisheries has been repeatedly proposed as a discard mitigation measure. A number of studies have assessed the fishing suitability of an area based on units of by-catch or discard per unit effort. However, correct identification of fishing-suitable areas should assess biomass loss with respect to the benefits. This study therefore, proposes the analysis of by-catch ratios, which do represent benefit vs. loss and are standardized to a wide range of effort characteristics. Furthermore, our study proposes the use of two ratios: the proportion of total unwanted biomass out of the total catch as an indicator of the overall ecological impact, and the proportion of unwanted but regulated species biomass as a proxy for the economic impact on fishers resulting from the new European discard ban that prohibits the discard of regulated species. These discard ratios are modelled by means of a Bayesian hierarchical model, specifically, a spatio-temporal beta regression model, which has several advantages over the traditional arcsine transformation. Results confirm the standardizing capacity of by-catch ratios across vessels and identify at least two economically fishing-suitable areas where discards ratios are minimized by reducing unwanted catch

Spatial Analysis of the Relationship between Mortality from Cardiovascular and Cerebrovascular Disease and Drinking Water Hardness

Previously published scientific papers have reported a negative correlation between drinking water hardness and cardiovascular mortality. Some ecologic and case–control studies suggest the protective effect of calcium and magnesium concentration in drinking water. In this article we present an analysis of this protective relationship in 538 municipalities of Comunidad Valenciana (Spain) from 1991–1998. We used the Spanish version of the Rapid Inquiry Facility (RIF) developed under the European Environment and Health Information System (EUROHEIS) research project. The strategy of analysis used in our study conforms to the exploratory nature of the RIF that is used as a tool to obtain quick and flexible insight into epidemiologic surveillance problems. This article describes the use of the RIF to explore possible associations between disease indicators and environmental factors. We used exposure analysis to assess the effect of both protective factors—calcium and magnesium—on mortality from cerebrovascular (ICD-9 430–438) and ischemic heart (ICD-9 410–414) diseases. This study provides statistical evidence of the relationship between mortality from cardiovascular diseases and hardness of drinking water. This relationship is stronger in cerebrovascular disease than in ischemic heart disease, is more pronounced for women than for men, and is more apparent with magnesium than with calcium concentration levels. Nevertheless, the protective nature of these two factors is not clearly established. Our results suggest the possibility of protectiveness but cannot be claimed as conclusive. The weak effects of these covariates make it difficult to separate them from the influence of socioeconomic and environmental factors. We have also performed disease mapping of standardized mortality ratios to detect clusters of municipalities with high risk. Further standardization by levels of calcium and magnesium in drinking water shows changes in the maps when we remove the effect of these covariates

El regadío del Ebro en Aragón: clasificación, contaminación y gobernanza

Grupo operativo Partenariado del Agua del Ebro-Aragó

The forward physics facility at the high-luminosity LHC

High energy collisions at the High-Luminosity Large Hadron Collider (LHC) produce a large number of particles along the beam collision axis, outside of the acceptance of existing LHC experiments. The proposed Forward Physics Facility (FPF), to be located several hundred meters from the ATLAS interaction point and shielded by concrete and rock, will host a suite of experiments to probe standard model (SM) processes and search for physics beyond the standard model (BSM). In this report, we review the status of the civil engineering plans and the experiments to explore the diverse physics signals that can be uniquely probed in the forward region. FPF experiments will be sensitive to a broad range of BSM physics through searches for new particle scattering or decay signatures and deviations from SM expectations in high statistics analyses with TeV neutrinos in this low-background environment. High statistics neutrino detection will also provide valuable data for fundamental topics in perturbative and non-perturbative QCD and in weak interactions. Experiments at the FPF will enable synergies between forward particle production at the LHC and astroparticle physics to be exploited. We report here on these physics topics, on infrastructure, detector, and simulation studies, and on future directions to realize the FPF's physics potential