Epithelial-to-mesenchymal transition involves triacylglycerol accumulation in DU145 prostate cancer cells

Epithelial to mesenchymal transition (EMT) is a biological process that plays a crucial role in cancer metastasis. Although studies regarding the EMT mechanisms are usual in terms of gene expression and protein functions, little is known about the involvement of lipids in EMT. In this work, an untargeted lipidomic analysis was performed to reveal which lipids are involved in the EMT process. DU145 prostate cancer cells were treated with TNFα, a well-known EMT inducer. After 6 hours of treatment, a decrease of cell membrane E-cadherin as well as a reduction in its gene expression were observed. Also, the mesenchymal markers Vimentin and Snail were up-regulated, suggesting that EMT started below 6 hours of treatment. Lipid extracts of untreated and TNFα-treated cells at short times were analyzed using ultra-performance liquid chromatography coupled to high-resolution mass spectrometry (UPLC-MS). Multivariate data analysis methods were applied to decipher which lipids presented significant changes after EMT induction. Among the results obtained, a significant increase of twelve unsaturated triacylglycerides (TAGs) was observed. This increase of TAGs was also observed for cells treated with TGFβ (another EMT inducer), suggesting that this feature is a common mechanism in the EMT process. In conclusion, this work reported for the first time a TAG accumulation through EMT induction. These TAG lipids could play a key role in providing cells with the energy, cell membrane components and signaling lipids necessary to guarantee the enhanced cell migration and proliferation of metastatic cells.This work was supported by the European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement 320737. J.J acknowledges a CSIC JAE-Doc contract cofounded by FSE.Peer reviewe

Urban data and urban design: A data mining approach to architecture education

The configuration of urban projects using Information and Communication Technologies is an essential aspect in the education of future architects. Students must know the technologies that will facilitate their academic and professional development, as well as anticipating the needs of the citizens and the requirements of their designs. In this paper, a data mining approach was used to outline the strategic requirements for an urban design project in an architecture course using a Project-Based Learning strategy. Informal data related to an award-winning public space (Gillett Square in London, UK) was retrieved from two social networks (Flickr and Twitter), and from its official website. The analysis focused on semantic, temporal and spatial patterns, aspects generally overlooked in traditional approaches. Text-mining techniques were used to relate semantic and temporal data, focusing on seasonal and weekly (work-leisure) cycles, and the geographic patterns were extracted both from geotagged pictures and by geocoding user locations. The results showed that it is possible to obtain and extract valuable data and information in order to determine the different uses and architectural requirements of an urban space, but such data and information can be challenging to retrieve, structure, analyze and visualize. The main goal of the paper is to outline a strategy and present a visualization of the results, in a way designed to be attractive and informative for both students and professionals - even without a technical background - so the conducted analysis may be reproducible in other urban data contexts.Postprint (author's final draft

Aproximació a les condicions del moviment de l'aigua en una conca experimental de Torre Marimon

Peer Reviewe

Cómo implementar el modelo centrado en la familia en la intervención temprana

A partir de los resultados de una investigación encaminada a la mejora de la calidad de vida de las familias con un hijo o hija con discapacidad intelectual, el objetivo del presente trabajo es ofrecer una propuesta metodológica para la implementación del modelo centrado en la familia en los centros de atención temprana de nuestro país. Los análisis cuantitativos y cualitativos de los datos recogidos nos permiten sistematizar los pasos o fases que sería necesario seguir con el fin de proporcionar herramientas útiles a los profesionales y a las familias de los centros de atención temprana para promover el desarrollo de los niños y el empoderamiento de las familias. El artículo supone un paso adelante respecto a las propuestas realizadas por otros investigadores de otros países con tradiciones y cultura diferentes en el ámbito de la atención temprana y trata de recoger las características y la idiosincrasia de nuestro país en cuanto a la historia y la trayectoria de la atención temprana en las últimas década

Estudio descriptivo de un modelo de orientación universitario

ABSTRACTThis study aims at describing the most relevant variables concerning the intervention carried out in the Personal Counseling Service at Faculty of Psicologia i Ciencies de l’Educació Blanquerna since 1997, and conducting a detailed analysis of the last two academic years in order to get to know the current situation. This is a descriptive and inferential cross-sectional study, with participation of 1,528 university students that have been attended to in the last 15 years. With regard to the first objective, the most outstanding results are the number of follow-up visits, which were 2,368, with a total number of in-person visits of 3,896, and an average number of visits per student of 2.54. Besides, 50% of attended students were followed up via email. With regard to the second objective, concerning the results of context of demand, 47.36% were academic, whereas 31.58% were at a personal level. Regarding the reason of demand, remarkably, 33.67% of undergraduates had learning difficulties. In conclusion, the opportunity that the European Higher Education Area (EHEA) offers us and our results give support to the sense of these services in the university setting, where it is transcendent to start or keep a healthy lifestyle at an integral level, bearing in mind academic, social and personal issues.RESUMENLos objetivos de este estudio son describir las variables más relevantes de la intervención realizada en el Servicio de Orientación Personal de la Facultad de Psicologia i Ciencies de l’Educació Blanquerna desde 1997 y realizar un análisis pormenorizado de los dos últimos cursos para conocer la situación actual. Se trata de un estudio descriptivo e inferencial de corte transversal, en el que participaron 1.528 estudiantes universitarios que fueron atendidos en los últimos 15 años. Respecto al primer objetivo, los resultados más destacados son el número de visitas de seguimiento, que fueron de 2.368, con un total de visitas presenciales de 3.896, por lo que el promedio de visitas por estudiante fue de 2.54. Además, el 50% de los alumnos atendidos realizaron seguimiento mediante el correo electrónico. Respecto al segundo objetivo, y en relación al contexto en el que se realizó la demanda, se destaca que un 47.36% fue académico frente el 31.58% que fue a nivel personal. En lo referente al motivo de demanda, destacar que el 33.67% de los estudiantes presentaron dificultades de aprendizaje. En conclusión, la oportunidad que nos ofrece el Espacio Europeo de Educación Superior (EEES) como los resultados obtenidos avalan el sentido de estos servicios en el marco universitario, donde es trascendente el inicio o el mantenimiento de un estilo de vida saludable a nivel psico-social, teniendo presentes tanto el ámbito académico como el personal y el social.ABSTRACTThis study aims at describing the most relevant variables concerning the intervention carried out in the Personal Counseling Service at Faculty of Psicologia i Ciencies de l’Educació Blanquerna since 1997, and conducting a detailed analysis of the last two academic years in order to get to know the current situation. This is a descriptive and inferential cross-sectional study, with participation of 1,528 university students that have been attended to in the last 15 years. With regard to the first objective, the most outstanding results are the number of follow-up visits, which were 2,368, with a total number of in-person visits of 3,896, and an average number of visits per student of 2.54. Besides, 50% of attended students were followed up via email. With regard to the second objective, concerning the results of context of demand, 47.36% were academic, whereas 31.58% were at a personal level. Regarding the reason of demand, remarkably, 33.67% of undergraduates had learning difficulties. In conclusion, the opportunity that the European Higher Education Area (EHEA) offers us and our results give support to the sense of these services in the university setting, where it is transcendent to start or keep a healthy lifestyle at an integral level, bearing in mind academic, social and personal issues.

Extremely low viral reservoir in treated chronically HIV-1-infected individuals

Altres ajuts: This research was sponsored in part by Grifols and by Merck Sharp & Dohme España, S.A. (IISP 54925). The funding organizations had no input in the design of the study; in the collection, analyses, or interpretation of the data; writing of the manuscript; or in the decision to submit the study for publication. NH received a post-doctoral grant from the Jaqueline Beytout Foundation. FG received the support of "José María Segovia de Arana" contracts (2019) and MMT from the NIH (R01AI143457).Small viral reservoirs are found predominantly in HIV-1 controllers and individuals treated during acute/early HIV-1 infection. However, other HIV + individuals could naturally also harbour low viral reservoirs. We screened 451 HIV-1-infected treated-individuals with suppressed plasma viremia for at least 3 years and stored cryopreserved peripheral blood mononuclear cells (PBMCs). Total HIV-DNA was analysed in PBMCs with ddPCR. Individuals with 50 HIV-DNA copies/10 6 PBMCs) to analyse total HIV-DNA, T-cell and NK-cell populations, HIV-1 specific antibodies, and plasma inflammation markers. We found that 9.3% of the individuals screened had <50 HIV-DNA copies/10 6 PBMCs. At least 66% initiated cART during the chronic phase of HIV-1 infection (cp-LoViReT). Cp-LoViReT harboured lower levels of HIV-DNA before cART and after treatment introduction the decays were greater compared to controls. They displayed a marked decline in quantity and avidity in HIV-specific antibodies after initiation of cART. Cp-LoViReT had fewer CD8 + T and T in the absence of cART, and higher CD8 + T after 18 months on therapy. Treated chronically HIV-1-infected LoViReT represent a new phenotype of individuals characterized by an intrinsically reduced viral reservoir, less impaired CD8 + T-cell compartment before cART, and low circulating HIV-1 antigens despite being treated in the chronic phase of infection. The identification of this unique group of individuals is of great interest for the design of future eradication studies. MSD Spai

Epilepsy surgery in drug resistant temporal lobe epilepsy associated with neuronal antibodies

We assessed the outcome of patients with drug resistant epilepsy and neuronal antibodies who underwent epilepsy surgery. Retrospective study, information collected with a questionnaire sent to epilepsy surgery centers. Thirteen patients identified, with antibodies to GAD (8), Ma2 (2), Hu (1), LGI1 (1) or CASPR2 (1). Mean age at seizure onset: 23 years. Five patients had an encephalitic phase. Three had testicular tumors and five had autoimmune diseases. All had drug resistant temporal lobe epilepsy (median: 20 seizures/month). MRI showed unilateral temporal lobe abnormalities (mainly hippocampal sclerosis) in 9 patients, bilateral abnormalities in 3, and was normal in 1. Surgical procedures included anteromesial temporal lobectomy (10 patients), selective amygdalohippocampectomy (1), temporal pole resection (1) and radiofrequency ablation of mesial structures (1). Perivascular lymphocytic infiltrates were seen in 7/12 patients. One year outcome available in all patients, at 3 years in 9. At last visit 5/13 patients (38.5%) (with Ma2, Hu, LGI1, and 2 GAD antibodies) were in Engel's classes I or II. Epilepsy surgery may be an option for patients with drug resistant seizures associated with neuronal antibodies. Outcome seems to be worse than that expected in other etiologies, even in the presence of unilateral HS. Intracranial EEG may be required in some patients

Organoid cultures recapitulate esophageal adenocarcinoma heterogeneity providing a model for clonality studies and precision therapeutics

Esophageal adenocarcinoma (EAC) incidence is increasing while 5-year survival rates remain less than 15%. A lack of experimental models has hampered progress. We have generated clinically annotated EAC organoid cultures that recapitulate the morphology, genomic and transcriptomic landscape of the primary tumor including point mutations, copy number alterations and mutational signatures. Karyotyping has confirmed polyclonality reflecting the clonal architecture of the primary and subclones underwent clonal selection associated with driver gene status. Medium throughput drug sensitivity testing demonstrates the potential of targeting receptor tyrosine kinases and downstream mediators. EAC organoid cultures provide a pre-clinical tool for studies of clonal evolution and precision therapeutics

Use of tocilizumab in kidney transplant recipients with COVID-1

Acute respiratory distress syndrome associated with coronavirus infection is related to a cytokine storm with large interleukin-6 (IL-6) release. The IL-6-receptor blocker tocilizumab may control the aberrant host immune response in patients with coronavirus disease 2019 (COVID-19) . In this pandemic, kidney transplant (KT) recipients are a high-risk population for severe infection and showed poor outcomes. We present a multicenter cohort study of 80 KT patients with severe COVID-19 treated with tocilizumab during hospital admission. High mortality rate was identified (32.5%), related with older age (hazard ratio [HR] 3.12 for those older than 60 years, P = .039). IL-6 and other inflammatory markers, including lactic acid dehydrogenase, ferritin, and D-dimer increased early after tocilizumab administration and their values were higher in nonsurvivors. Instead, C-reactive protein (CRP) levels decreased after tocilizumab, and this decrease positively correlated with survival (mean 12.3 mg/L in survivors vs. 33 mg/L in nonsurvivors). Each mg/L of CRP soon after tocilizumab increased the risk of death by 1% (HR 1.01 [confidence interval 1.004-1.024], P = .003). Although patients who died presented with worse respiratory situation at admission, this was not significantly different at tocilizumab administration and did not have an impact on outcome in the multivariate analysis. Tocilizumab may be effective in controlling cytokine storm in COVID-19 but randomized trials are needed

Mutational signatures in esophageal adenocarcinoma define etiologically distinct subgroups with therapeutic relevance.

Esophageal adenocarcinoma (EAC) has a poor outcome, and targeted therapy trials have thus far been disappointing owing to a lack of robust stratification methods. Whole-genome sequencing (WGS) analysis of 129 cases demonstrated that this is a heterogeneous cancer dominated by copy number alterations with frequent large-scale rearrangements. Co-amplification of receptor tyrosine kinases (RTKs) and/or downstream mitogenic activation is almost ubiquitous; thus tailored combination RTK inhibitor (RTKi) therapy might be required, as we demonstrate in vitro. However, mutational signatures showed three distinct molecular subtypes with potential therapeutic relevance, which we verified in an independent cohort (n = 87): (i) enrichment for BRCA signature with prevalent defects in the homologous recombination pathway; (ii) dominant T>G mutational pattern associated with a high mutational load and neoantigen burden; and (iii) C>A/T mutational pattern with evidence of an aging imprint. These subtypes could be ascertained using a clinically applicable sequencing strategy (low coverage) as a basis for therapy selection.Whole-genome sequencing of esophageal adenocarcinoma samples was performed as part of the International Cancer Genome Consortium (ICGC) through the oEsophageal Cancer Clinical and Molecular Stratification (OCCAMS) Consortium and was funded by Cancer Research UK. We thank the ICGC members for their input on verification standards as part of the benchmarking exercise. We thank the Human Research Tissue Bank, which is supported by the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, from Addenbrooke’s Hospital and UCL. Also the University Hospital of Southampton Trust and the Southampton, Birmingham, Edinburgh and UCL Experimental Cancer Medicine Centres and the QEHB charities. This study was partly funded by a project grant from Cancer Research UK. R.C.F. is funded by an NIHR Professorship and receives core funding from the Medical Research Council and infrastructure support from the Biomedical Research Centre and the Experimental Cancer Medicine Centre. We acknowledge the support of The University of Cambridge, Cancer Research UK (C14303/A17197) and Hutchison Whampoa Limited. We would like to thank Dr. Peter Van Loo for providing the NGS version of ASCAT for copy number calling. We are grateful to all the patients who provided written consent for participation in this study and the staff at all participating centres. Some of the work was undertaken at UCLH/UCL who received a proportion of funding from the Department of Health’s NIHR Biomedical Research Centres funding scheme. The work at UCLH/UCL was also supported by the CRUK UCL Early Cancer Medicine Centre.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.365