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SUMMARYTristetraprolin (TTP) is a RNA binding protein that destabilizes mRNA of factors that up-regulate proliferation, invasiveness and inflammation. Here we show that TTP expression is higher in mammary progenitor cells than in other cell populations, and that reducing its levels impairs mammary gland morphogenesisin vivoand mammosphere formation in culture. Knocking down TTP in stem-like HC11 mouse mammary cell line increased inflammatory cytokine mRNAs and signaling cascades involving NFκB, STAT3 and MAPK p38 activation, which led to apoptosis. Importantly, TNFα overexpression and the consequent p38 phosphorylation would be the leading cause of progenitor cell death upon TTP expression restriction. Taken together, our results reveal the relevance of negative posttranscriptional regulation on TNFα, exerted by TTP, for the maintenance of the progenitor cell compartment in the mammary gland.

ICT has become increasingly prevalent in the development and provision of social services for children and families. ICT has enabled social innovation in children’s services and the wider social services sector through its contribution to the transformation of service management and implementation, cost-efficiency improvement and the effectiveness of service delivery. ICT-enabled social innovation (IESI) can help to address the increased demand on social welfare services, for example through improved coordination between professionals and enhanced communication with service users. These changes are presented through a number of case studies of ICT in children’s services in Europe. One of these is the development of tools for data collection by the National Child Protection Observatory in cooperation with local authorities in France. Another example is the KOMBIT standardised ICT system for the case management of children at risk in Denmark. One further example is Alborada, a shared information system in Andalucía (Spain), which facilitates data sharing and coordination between professionals from health, education and social services working with children with developmental difficulties. The analysis of the case studies has allowed the formulation of some key recommendations for the development of ICT-enabled innovation in children’s services in terms of the role that policy can play in driving forward ICT-enabled services, ICT’s role in meeting children’s needs, and professionals’ training and development for the successful introduction and implementation of ICT in children’s services.

Breast cancer (BC) is the leading cause of cancer-related mortality in women, only followed by lung cancer. Given the importance of BC in public health, it is essential to identify biomarkers to predict prognosis, predetermine drug resistance and provide treatment guidelines that include personalized targeted therapies. The Hedgehog (Hh) signaling pathway plays an essential role in embryonic development, tissue regeneration, and stem cell renewal. Several lines of evidence endorse the important role of canonical and non-canonical Hh signaling in BC. In this comprehensive review we discuss the role of Hh signaling in breast development and homeostasis and its contribution to tumorigenesis and progression of different subtypes of BC. We also examine the efficacy of agents targeting different components of the Hh pathway both in preclinical models and in clinical trials. The contribution of the Hh pathway in BC tumorigenesis and progression, its prognostic role, and its value as a therapeutic target vary according to the molecular, clinical, and histopathological characteristics of the BC patients. The evidence presented here highlights the relevance of the Hh signaling in BC, and suggest that this pathway is key for BC progression and metastasis. Fil: Riobo Del Galdo, Natalia A.. University Of Leeds.; Reino Unido Fil: Lara Montero, Angela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina Fil: Wertheimer Hermitte, Eva Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina

Resumen basado en el de la publicación Título, resumen y palabras clave en español y en inglés Se pretende hacer un recorrido por la legislación española en materia educativa, a lo largo de la etapa democrática, estudiando los antecedentes ideológicos que servirán de base para el nacimiento de las llamadas “competencias básicas” y que, a su vez, evolucionarán hacia el concepto europeo de “competencias clave”. Para ello se analizarán los preámbulos, fines, principios y objetivos de las siguientes leyes: Ley Orgánica Reguladora del Derecho a la Educación (LODE), Ley de Ordenación General del Sistema Educativo (LOGSE), Ley de Calidad de la Educación (LOCE), Ley Orgánica de Educación (LOE) y, por último, la actual Ley para la Mejora de la Calidad Educativa (LOMCE), así como las directrices europeas que orientan los sistemas educativos de los países miembros. ESP

Background Worldwide, Breast cancer (BC) is the leading cause of cancer-related mortality in women. In Argentina, breast cancer is the second leading cause of death in women, with an incidence of 18.47%. Given the importance of breast cancer for public health, and the diversity of patients’ response to current therapies, the identification of new therapeutic targets is crucial. Rac1 is a Rho GTPase widely involved in motility, mitogenesis, transformation, and metastasis. P-Rex1 is a Rac1 activator essential for the migration of breast cancer cells. It has been reported that P-Rex1 is overexpressed in breast cancer of the luminal type and that its silencing inhibits the migration of cancer cells. In order to validate P-Rex1 as a therapeutic target and/or prognostic biomarker, we aimed to analyze its presence in samples of Argentinean patients from the Marie Curie Hospital of Buenos Aires City, and determine its relationship with clinical and histopathological parameters. Methods The levels of P-Rex1 were determined both in biopsy material and in tumor tissue (and its corresponding healthy adjacent tissue) from primary surgery of patients not undergoing neoadjuvant therapy. The levels of messenger RNA (mRNA) were analyzed by quantitative PCR and protein by western blot (WB) and immunohistochemistry. Results When the mRNA levels of the biopsies classified according to the molecular subtype were compared, elevated P-Rex1 levels were observed not only in those samples classified as ER+/PR+ breast cancer but also in 50% of the samples of triple negative breast cancer (TNBC). These data were validated by an in-silico analysis made from public access databases (Metabric and the GEO repository of NCBI). P-Rex overexpression in TNBC patients has not been previously reported. The aberrant expression of P-Rex1 was detected in all stages of the disease, and a negative correlation between the expression of P-REX1 and the proliferation marker Ki-67 was determined. P-Rex1 levels were significantly higher in tumors compared to normal breast samples, in agreement with previous reports. Conclusions These results confirm the potential of P-Rex1 as a therapeutic target not only for the treatment of luminal tumors but also for a certain population of TNBC patients. Legal entity responsible for the study Eva Wertheimer. Funding Instituto Nacional del Cancer-Ministerio de Salud-Argentina (INC, Asistencia Financiera IV, 2018). Disclosure All authors have declared no conflicts of interest.

En este artículo queremos avanzar resultados obtenidos en la intervención puntual realizada en el asentamiento calco lítico del Parque de Miraflores. La intervención consistió en la delimitación del asentamiento y en la excavación de dos estructuras siliformes con diversos procesos de colmatación bien definidos. Las dataciones por AMS obtenidas estratigráficamente aportan una amplitud cronológica para el asentamiento desde el 2937 al 2576 cal BC. In this paper we want to present some of the results obtained in the archaelogical works realised in the chalcolithic settlement of El Parque de Miraflores (Sevilla, Spain). These works consisted on the complete delimitation of the settlement and the excavation of two siloshape estructures in which different well-defined depositional processes were documented. The stratified AMS datings give a cronological range for the settlement from 2937 to 2576 cal BC.

Across Europe, when people talk about “integration” they may refer to structural re-organisation and improved governance; for instance, having a single accountable agency responsible for commissioning services. Others mean improving cooperation between professionals from different sectors working with the same client. There are yet more who refer to integrating various strands of finance by pooling budgets or creating specific integrated funds to support specific groups with complex needs. They are all important and in some form or another they are all integration, but do they improve people’s outcomes? The term 'integrated services' has come up over the years in many of the activities and projects organised by the European Social Network but we realised that the understanding of the term differs considerably across Europe. That is why we defined the term “integrated services” as the range of activities, depending on sectors, target groups and governance contexts, implemented to achieve more efficient coordination between services and improved outcomes for service users. Forms of service integration are manifold, depending on sectors, target groups, governance level -local, regional and national, the objectives and the level of integration between two or more public bodies. In this context, the European Social Network has been cooperating closely with the Dutch centre for expertise on long-term care -Vilans in a 2 year project that aimed to analyse how social services provide integrated support with other public services, namely education, employment and health. We developed a methodology through a literature and practice review and identified examples of case-management approaches that assess, plan and coordinate service delivery; one-stop-shops where services are provided by a single point of contact, and partnership arrangements where two or more organisations pool budgets or multi-professional teams (also including users) at local level. At the workshop we will highlight how changes in the care landscape may benefit service users as support becomes more holistic. We will start by reviewing how integrated support requires new skills and new ways of working; including new roles, new career paths and joint training. We will also review key enablers in the process, including technology, policy and financing mechanisms. Next, we will feature examples of practices combining several of these key enablers. These examples will help us to illustrate that integration is not only about making organisational, governance, budgetary, structural or cultural changes but most importantly the i-word is about people. We have learned from this exercise that a key requirement for social care to be part of integrated care models is the need to invest in the organisations’ learning environment, joint training, skills development and in the human side of professionals’ relationships. This may include trust-building, common understanding and common assessment having always as the ultimate aim ensuring people's social inclusion and improving their quality of life.