Fat1 deletion promotes hybrid EMT state, tumour stemness and metastasis

FAT1, which encodes a protocadherin, is one of the most frequently mutated genes in human cancers1–5. However, the role and the molecular mechanisms by which FAT1 mutations control tumour initiation and progression are poorly understood. Here, using mouse models of skin squamous cell carcinoma and lung tumours, we found that deletion of Fat1 accelerates tumour initiation and malignant progression and promotes a hybrid epithelial-to-mesenchymal transition (EMT) phenotype. We also found this hybrid EMT state in FAT1-mutated human squamous cell carcinomas. Skin squamous cell carcinomas in which Fat1 was deleted presented increased tumour stemness and spontaneous metastasis. We performed transcriptional and chromatin profiling combined with proteomic analyses and mechanistic studies, which revealed that loss of function of FAT1 activates a CAMK2–CD44–SRC axis that promotes YAP1 nuclear translocation and ZEB1 expression that stimulates the mesenchymal state. This loss of function also inactivates EZH2, promoting SOX2 expression, which sustains the epithelial state. Our comprehensive analysis identified drug resistance and vulnerabilities in FAT1-deficient tumours, which have important implications for cancer therapy. Our studies reveal that, in mouse and human squamous cell carcinoma, loss of function of FAT1 promotes tumour initiation, progression, invasiveness, stemness and metastasis through the induction of a hybrid EMT state

Diagnostic accuracy of a clinical diagnosis of idiopathic pulmonary fibrosis: An international case-cohort study

We conducted an international study of idiopathic pulmonary fibrosis (IPF) diagnosis among a large group of physicians and compared their diagnostic performance to a panel of IPF experts. A total of 1141 respiratory physicians and 34 IPF experts participated. Participants evaluated 60 cases of interstitial lung disease (ILD) without interdisciplinary consultation. Diagnostic agreement was measured using the weighted kappa coefficient (\u3baw). Prognostic discrimination between IPF and other ILDs was used to validate diagnostic accuracy for first-choice diagnoses of IPF and were compared using the Cindex. A total of 404 physicians completed the study. Agreement for IPF diagnosis was higher among expert physicians (\u3baw=0.65, IQR 0.53-0.72, p20 years of experience (C-index=0.72, IQR 0.0-0.73, p=0.229) and non-university hospital physicians with more than 20 years of experience, attending weekly MDT meetings (C-index=0.72, IQR 0.70-0.72, p=0.052), did not differ significantly (p=0.229 and p=0.052 respectively) from the expert panel (C-index=0.74 IQR 0.72-0.75). Experienced respiratory physicians at university-based institutions diagnose IPF with similar prognostic accuracy to IPF experts. Regular MDT meeting attendance improves the prognostic accuracy of experienced non-university practitioners to levels achieved by IPF experts

Tecnologías de membranas líquidas soportadas en la eliminación de metales de efluentes líquidos

The generation of liquid effluents containing organic and inorganic residues from industries present a potential hazardousness for environment and human health, being mandatory the elimination of these pollutants from the respective solutions containing them. In order to achieve this goal, several techniques are being used and among them, supported liquid membranes technologies are showing their potential for their application in the removal of metals contained in liquid effluents. Supported liquid membranes are a combination between conventional polymeric membranes and solvent extraction. Several configurations are used: flat-sheet supported liquid membranes, spiral wounds and hollow fiber modules. In order to improve their effectiveness, smart operations have been developed: non-dispersive solvent extraction, non-dispersive solvent extraction with strip phase dispersion and hollow fiber renewal liquid membrane. This paper overviewed some of these supported liquid membranes technologies and their applications to the treatment of metal-bearing liquid effluents.La generación, por parte de las industrias, de efluentes líquidos conteniendo sustancias orgánicas e inorgánicas, es un peligro potencial tanto para los humanos como para el medio ambiente, siendo necesaria la eliminación de estos elementos tóxicos de las disoluciones que los contienen. Para conseguir este fin, se están aplicando diversas técnicas y entre ellas las tecnologías de membranas líquidas soportadas, están demostrando sus aptitudes para la eliminación de metales contenidos en efluentes líquidos. Las membranas líquidas soportadas, resultan de la unión de las membranas poliméricas y de la tecnología de extracción líquido-líquido. Este tipo de membranas se pueden utilizar en diversas configuraciones: plana, módulo en fibra hueca y módulo en espiral y para aumentar su efectividad se están desarrollando las llamadas operaciones avanzadas: extracción no dispersiva, extracción no dispersiva con dispersión de la fase de reextracción y empleo del módulo de fibra hueca, con renovación de la membrana líquida. En este trabajo se revisan estas operaciones de membranas líquidas soportadas y algunas de las aplicaciones de las mismas, en el tratamiento de efluentes líquidos conteniendo metales.To the CENIM (CSIC) for support and Dra I. García-Díaz the contract JAEDoc_09_00893, CSIC.Peer reviewe

The sustainability of the Barcelona port enlargement works

In the Barcelona Port enlargement, currently under construction, part of the new quays are being backfilled with re-used materials such as tunneling waste, rubble from demolitions and dredged soils with poor geotechnical properties. This has resulted in a cost-effective and sustainable construction process that is one of the main goals of the Barcelona Port Authority (APB). A series of control tests have been carried out on the mentioned materials. In addition, dredged soils have been improved by preloading, a procedure that has been closely monitored by instrumentation. Very satisfactory results have been achieved by this re-use program both in terms of cost and of sustainability.Postprint (published version

The sustainability of the Barcelona port enlargement works

In the Barcelona Port enlargement, currently under construction, part of the new quays are being backfilled with re-used materials such as tunneling waste, rubble from demolitions and dredged soils with poor geotechnical properties. This has resulted in a cost-effective and sustainable construction process that is one of the main goals of the Barcelona Port Authority (APB). A series of control tests have been carried out on the mentioned materials. In addition, dredged soils have been improved by preloading, a procedure that has been closely monitored by instrumentation. Very satisfactory results have been achieved by this re-use program both in terms of cost and of sustainability