The Jak2 Pathway Is Activated In Idiopathic Pulmonary Fibrosis

Background: Idiopathic pulmonary fibrosis (IPF) is the most rapidly progressive and fatal fibrotic disorder, with no curative therapies. The signal transducer and activator of transcription 3 (STAT3) protein is activated in lung fibroblasts and alveolar type II cells (ATII), thereby contributing to lung fibrosis in IPF. Although activation of Janus kinase 2 (JAK2) has been implicated in proliferative disorders, its role in IPF is unknown. The aim of this study was to analyze JAK2 activation in IPF, and to determine whether JAK2/STAT3 inhibition is a potential therapeutic strategy for this disease. Methods and results: JAK2/p-JAK2 and STAT3/pSTAT3 expression was evaluated using quantitative real time-PCR, western blotting, and immunohistochemistry. Compared to human healthy lung tissue (n = 10) both proteins were upregulated in the lung tissue of IPF patients (n = 12). Stimulating primary ATII and lung fibroblasts with transforming growth factor beta 1 or interleukin (IL)-6/IL-13 activated JAK2 and STAT3, inducing epithelial to mesenchymal and fibroblast to myofibroblast transitions. Dual p-JAK2/p-STAT3 inhibition with JSI-124 or silencing of JAK2 and STAT3 genes suppressed ATII and the fibroblast to myofibroblast transition, with greater effects than the sum of those obtained using JAK2 or STAT3 inhibitors individually. Dual rather than single inhibition was also more effective for inhibiting fibroblast migration, preventing increases in fibroblast senescence and Bcl-2 expression, and ameliorating impaired autophagy. In rats administered JSI-124, a dual inhibitor of p-JAK2/p-STAT3, at a dose of 1 mg/kg/day, bleomycin-induced lung fibrosis was reduced and collagen deposition in the lung was inhibited, as were JAK2 and STAT3 activation and several markers of fibrosis, autophagy, senescence, and anti-apoptosis. Conclusions: JAK2 and STAT3 are activated in IPF, and their dual inhibition may be an attractive strategy for treating this disease

La Covacha del barranco de los Frailes (Mosqueruela, Teruel): una pequeña cavidad sepulcral de la Edad del Bronce

Se presentan los resultados de la excavación de una pequeña cavidad sepulcral de la Edad del Bronce en el límite entre las provincias de Teruel y Castellón. Diversos aspectos centran el interés de su estudio más allá del necesario examen antropológico y elementos de cultura material, como son la documentación de la posible estructura de cierre, la obtención de dataciones radiocarbónicas y el análisis detallado de la fauna. Los resultados refuerzan la necesidad de efectuar este tipo de intervenciones para avanzar en el conocimiento de las prácticas funerarias del III y II milenio a. C. en el este de la península ibérica. This paper presents the results of the excavation of a small Bronze Age burial chamber located on the border between the provinces of Teruel and Castelló. Beyond the simple necessary anthropological study and analysis of material remains, various other aspects have been addressed such as the documentation of the possible enclosing structure, the fixing of radiocarbon dates and the detailed analysis of the faunal remains. The results further confirm the need for this type of excavation and research in order to advance our knowledge of funerary practices during the 3rd and 2nd millennium BC in the eastern part of the Iberian Peninsula

Loss of microRNA-135b Enhances Bone Metastasis in Prostate Cancer and Predicts Aggressiveness in Human Prostate Samples

About 70% of advanced-stage prostate cancer (PCa) patients will experience bone metastasis, which severely affects patients' quality of life and progresses to lethal PCa in most cases. Hence, understanding the molecular heterogeneity of PCa cell populations and the signaling pathways associated with bone tropism is crucial. For this purpose, we generated an animal model with high penetrance to metastasize to bone using an intracardiac percutaneous injection of PC3 cells to identify PCa metastasis-promoting factors. Using genomic high-throughput analysis we identified a miRNA signature involved in bone metastasis that also presents potential as a biomarker of PCa progression in human samples. In particular, the downregulation of miR-135b favored the incidence of bone metastases by significantly increasing PCa cells' migratory capacity. Moreover, the PLAG1, JAKMIP2, PDGFA, and VTI1b target genes were identified as potential mediators of miR-135b's role in the dissemination to bone. In this study, we provide a genomic signature involved in PCa bone growth, contributing to a better understanding of the mechanisms responsible for this process. In the future, our results could ultimately translate into promising new therapeutic targets for the treatment of lethal PCa

The Scelidotheriine Proscelidodon (Xenarthra: Mylodontidae) from the Late Miocene of Maimará (Northwestern Argentina)

Xenarthra constitutes one of the most peculiar clades of the South American mammalian fauna and includes sloths (Tardigrada), anteaters (Vermilingua), and armored xenarthrans (Cingulata). Its phylogenetic affinities among placental mammals and their origins remain doubtful (Asher and Helgen, 2010). Xenarthrans first appear in the Itaboraian age (late Paleocene?early Eocene; Oliveira and Goin, 2011) represented by the Dasypodidae in the locality of Itaboraí, Brazil. Sloths are first recorded from the early Oligocene (Tinguirirican age) of Chile and became abundant during the late Oligocene (Deseadan age), mainly in Argentina and Bolivia with representation of Mylodontidae and Megalonychidae (Pujos et al., 2012).Fil: Pujos, François Roger Francis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; ArgentinaFil: Candela, Adriana Magdalena. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. División Paleontología Vertebrados; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Galli, Claudia Inés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Salta; ArgentinaFil: Coira, Beatriz Lidia Luisa. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Reguero, Marcelo Alfredo. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. División Paleontología Vertebrados; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: De los Reyes, Martín. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo; ArgentinaFil: Abello, María Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Laboratorio de Sistemática y Biología Evolutiva; Argentin

Habilidades para la vida

In 1993, the World Health Organization proposed a psychosocial development approach called life skills; Its objective was to prevent and intervene in problems related to drug use, crime, and risky sexual behaviors, among others. Since then, programs based on this approach have been implemented to address various risk situations. The book “Skills for life. Conceptual Approaches ” presents updated theoretical contributions of life skills, including cognitive, emotional, and social skills, with a perspective aimed at promoting mental health and human growth. The theoretical contributions presented can help psychosocial professionals such as psychologists, pedagogues, family therapists, and other actors who work with people at psychosocial risk. They also constitute a conceptual basis for the Life Skills approach.illustratorEn 1993, la Organización Mundial de la Salud propuso un enfoque de desarrollo psicosocial denominado Habilidades para la vida; su objetivo era prevenir e intervenir en problemas relacionados con el consumo de drogas, la delincuencia y los comportamientos sexuales de riesgo, entre otros. Desde entonces, se han implementado programas basados en este enfoque para abordar diversas situaciones de riesgo. El libro “Habilidades para la vida. Aproximaciones conceptuales” presenta aportes teóricos actualizados de las Habilidades para la vida, que incluyen las habilidades cognitivas, emocionales y sociales, con una perspectiva orientada a favorecer la salud mental y el crecimiento humano. Los aportes teóricos expuestos pueden ayudar a los profesionales psicosociales como psicólogos, pedagogos, terapeutas familiares y otros actores que trabajan con personas en riesgo psicosocial. Asimismo, constituyen una base conceptual para fundamentar el enfoque de Habilidades para la vida

FURNISH : new methodologies to intervene in public space

Descripció del recurs: 23 maig 2023FURNISH is the acronym of Fast Urban Responses for New Inclusive Spaces and Habitat, a project centred on transforming streets by repurposing them. The project was born during the COVID-19 pandemic, when the emergency triggered the need to creatively reframe the general understanding, not only of our behaviour, but also of our environment. Public spaces should evolve and become more inclusive places for everyone, especially for the most vulnerable. Under these challenging circumstances, FURNISH, a project led by CARNET, emerged to rethink the public space, while taking action in an inclusive and necessary manner. This book summarises the project since its inception in 2020, the new methodologies applied to intervene the public space, and the fantastic experimental results. Enjoy the book!

Transcription factors relevant to auxin signalling coordinate broad-spectrum metabolic shifts including sulphur metabolism

A systems approach has previously been used to follow the response behaviour of Arabidopsis thaliana plants upon sulphur limitation. A response network was reconstructed from a time series of transcript and metabolite profiles, integrating complex metabolic and transcript data in order to investigate a potential causal relationship. The resulting scale-free network allowed potential transcriptional regulators of sulphur metabolism to be identified. Here, three sulphur-starvation responsive transcription factors, IAA13, IAA28, and ARF-2 (ARF1-Binding Protein), all of which are related to auxin signalling, were selected for further investigation. IAA28 overexpressing and knock-down lines showed no major morphological changes, whereas IAA13- and ARF1-BP-overexpressing plants grew more slowly than the wild type. Steady-state metabolite levels and expression of pathway-relevant genes were monitored under normal and sulphate-depleted conditions. For all lines, changes in transcript and metabolite levels were observed, yet none of these changes could exclusively be linked to sulphur stress. Instead, up- or down-regulation of the transcription factors caused metabolic changes which in turn affected sulphur metabolism. Auxin-relevant transcription factors are thus part of a complex response pattern to nutrient starvation that serve as coordinators of the metabolic shifts driving sulphur homeostasis rather then as direct effectors of the sulphate assimilation pathway. This study provides the first evidence ever presented that correlates auxin-related transcriptional regulators with primary plant metabolism

Iniciativas de fomento de las vocaciones STEAM

Este pretende ser un directorio de iniciativas que fomentan las vocaciones STEAM (ciencia, tecnología, ingeniería, arte y matemáticas) cuyo ámbito de acción es la Comunitat Valenciana. Según el último informe PISA, existe una marcada diferencia entre la cantidad de chicas y chicos que eligen profesiones relacionadas con la ciencia y la ingeniería. Solo el 5,2% de las chicas esperan trabajar en estas áreas, mientras que el porcentaje de chicos asciende al 15,3%. En cambio, el porcentaje de chicas que eligen las ciencias de la salud es del 19,8%, mientras que solo el 6,9% de los chicos elige esta área. El estudio "Radiografía de la brecha de género en la formación STEAM" del Ministerio de Educación y Formación Profesional revela que la brecha de género se reproduce en todas las etapas educativas, desde la elección de asignaturas que puntúan en la Prueba de Acceso a la Universidad hasta la elección de programas de Formación Profesional y estudios universitarios. Por ejemplo, en los ciclos de Formación Profesional de Informática y Comunicaciones, solo el 10% de las matrículas son chicas, mientras que en los ciclos de Sanidad superan el 75%. En la universidad, solo el 25% de las mujeres elige grados STEAM, y en Ingeniería Informática ese porcentaje desciende al 12,74%. Sin embargo, en los grados de Ciencias de la Naturaleza y la Salud, las chicas representan una mayoría en áreas como Enfermería (81,75%), Biomedicina (75,08%) y Medicina (68,71%). Estos datos indican que las chicas tienden a elegir carreras relacionadas con los cuidados, mientras que los chicos se inclinan por estudios técnicos y tecnológicos. Esto no es casual, sino que refleja la influencia de estereotipos y roles de género arraigados en la sociedad, lo que crea barreras culturales y prácticas discriminatorias. La baja presencia de mujeres en los campos técnicos y tecnológicos también contribuye y es resultado de la segunda y tercera brecha digital de género. La segunda brecha digital se refiere a las diferencias en habilidades, competencias y uso de la tecnología entre hombres y mujeres. La tercera brecha digital se basa en tres deficiencias: la brecha en el uso avanzado de la tecnología, la brecha en la inclusión de las perspectivas y necesidades de las mujeres y la brecha en los sectores profesionales relacionados con las TIC. Despertar el interés de las niñas y adolescentes en las vocaciones STEAM se ha convertido en un desafío importante, ya que el mercado laboral demanda cada vez más perfiles en estas áreas. El estudio analiza 30 iniciativas de fomento de las vocaciones STEAM en la Comunitat Valenciana con el objetivo de compartir buenas prácticas y servir de inspiración para futuros proyectos. El informe incluye un decálogo de buenas prácticas para impulsar el talento científico, tecnológico, ingeniero, matemático y creativo en las chicas. Las iniciativas recopiladas se obtuvieron a través de un cuestionario enviado enviado a entidades y organizaciones involucradas en la promoción de las vocaciones STEAM, especialmente entre las mujeres. Se registraron 43 proyectos en total, pero solo se presentan las 30 iniciativas seleccionadas que se centran en el fomento de las vocaciones STEAM. Aquellas que no se incluyen tienen objetivos diferentes pero contribuyen a visibilizar las profesiones STEAM. Cabe destacar que el informe no pretende ser un catálogo exhaustivo de todas las iniciativas en la Comunitat Valenciana, pero las 30 recopiladas proporcionan una muestra representativa de las acciones realizadas y de quiénes las impulsan. El informe se estructura en cinco apartados: introducción, metodología, tabla de síntesis de las 30 iniciativas, análisis descriptivo de las iniciativas y un decálogo de buenas prácticas. También se incluye un anexo con fichas informativas sobre cada una de las 30 iniciativas seleccionadas, que contienen detalles como el tipo de actividad, el público objetivo y los indicadores de evaluación. El informe ofrece un multi-índice para facilitar la búsqueda de iniciativas según diferentes criterios, como género, provincia, etapa educativa y tipo de actividad

Cereal yield gaps across Europe

peer-reviewedEurope accounts for around 20% of the global cereal production and is a net exporter of ca. 15% of that production. Increasing global demand for cereals justifies questions as to where and by how much Europe’s production can be increased to meet future global market demands, and how much additional nitrogen (N) crops would require. The latter is important as environmental concern and legislation are equally important as production aims in Europe. Here, we used a country-by-country, bottom-up approach to establish statistical estimates of actual grain yield, and compare these to modelled estimates of potential yields for either irrigated or rainfed conditions. In this way, we identified the yield gaps and the opportunities for increased cereal production for wheat, barley and maize, which represent 90% of the cereals grown in Europe. The combined mean annual yield gap of wheat, barley, maize was 239 Mt, or 42% of the yield potential. The national yield gaps ranged between 10 and 70%, with small gaps in many north-western European countries, and large gaps in eastern and south-western Europe. Yield gaps for rainfed and irrigated maize were consistently lower than those of wheat and barley. If the yield gaps of maize, wheat and barley would be reduced from 42% to 20% of potential yields, this would increase annual cereal production by 128 Mt (39%). Potential for higher cereal production exists predominantly in Eastern Europe, and half of Europe’s potential increase is located in Ukraine, Romania and Poland. Unlocking the identified potential for production growth requires a substantial increase of the crop N uptake of 4.8 Mt. Across Europe, the average N uptake gaps, to achieve 80% of the yield potential, were 87, 77 and 43 kg N ha−1 for wheat, barley and maize, respectively. Emphasis on increasing the N use efficiency is necessary to minimize the need for additional N inputs. Whether yield gap reduction is desirable and feasible is a matter of balancing Europe’s role in global food security, farm economic objectives and environmental targets.We received financial contributions from the strategic investment funds (IPOP) of Wageningen University & Research, Bill & Melinda Gates Foundation, MACSUR under EU FACCE-JPI which was funded through several national contributions, and TempAg (http://tempag.net/)

Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia

Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P=5.04 × 10−13), 1q42.13 (rs41271473, P=1.06 × 10−10), 4q24 (rs71597109, P=1.37 × 10−10), 4q35.1 (rs57214277, P=3.69 × 10−8), 6p21.31 (rs3800461, P=1.97 × 10−8), 11q23.2 (rs61904987, P=2.64 × 10−11), 18q21.1 (rs1036935, P=3.27 × 10−8), 19p13.3 (rs7254272, P=4.67 × 10−8) and 22q13.33 (rs140522, P=2.70 × 10−9). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for the key determinants of B-cell development and immune response