34 research outputs found

    Plan local de empleo municipio de Medellín

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    RESUMEN: La formulación del Plan Local de Empleo para la ciudad de Medellín significa la materialización de los compromisos en materia de promoción de la Política Pública de Trabajo Decente, a través de un componente estratégico que ponga en marcha medidas integrales, acciones, programas y proyectos que creen y mantegan el trabajo decente. En adición, el PLE se artícula con la política de desarrollo económico, eje rector del crecimiento económico y empresarial, con el que cuenta la ciudad. El PLE presenta cuatro capítulos en los cuales se describe la información compilada de los actores del mercado de trabajo. El primer capítulo presenta los elementos fundamentales de la política pública de trabajo decente y el plan local de empleo. El segundo capítulo da cuenta del componente estratégico, en el cual se describen los principales elementos metodológicos del PLE. El tercer capítulo relaciona el PLE con los Objetivos del Desarrollo Sostenible (ODS). Finalmente, el último apartado señala los lineamientos estratégicos del Plan Local de Empleo, diferenciando cada uno de los ejes o categorias fundamentales del trabajo decente en Medellín.1. Introducción 2. Regulación jurídica del trabajo decente 3. La política pública del trabajo decente y el plan local de empleo 4. Componente estratégico del plan local de empleo 5. El plan local de empleo y los ODS 6. Lineamientos estratégicos del plan local de emple

    First evidence of paleoearthquakes along the Carboneras Fault Zone (SE Iberian Peninsula) : Los Trances site

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    Seismogenic faults that have not produced historical large earthquakes remain unnoticed and, thus, are dangerously left out from seismic hazard analyses. The seismogenic nature of the Carboneras Fault Zone, a left-lateral strikeslip fault in the Eastern Betic Shear Zone (southeastern Spain), has not been fully explored to date in spite of having a morphological expression equivalent to the Alhama de Murcia Fault, a seismogenic fault in the same tectonic system. This study provides the first paleoseismic evidence of the seismogenic nature of the CarbonerasFault Zone, based on the analysis of 3 trenches at Los Trances site, on the northwestern edge of the La Serrata Range. Cross cutting relationships and numerical dating, based on radiocarbon, thermoluminescence and U-series, reveal a minimum of 4 paleoearthquakes: Paleoearthquake1 (the oldest) and Paleoearthquake2 took place after 133ka, Paleoearthquake3 occurred between 83-73ka and Paleoearthquake4 happened after 42.5ka (probably after 30.8ka), resulting in a maximum possible average recurrence of 33ka. This value, based on a minimum amount of paleoearthquakes, is probably overestimated, as it does not scale well with published slip-rates derived from offset channels or GPS geodetical data. The characterization of this fault as seismogenic, implies that it should be considered in the seismic hazard analyses of the SE Iberian Peninsula

    The European Reference Genome Atlas: piloting a decentralised approach to equitable biodiversity genomics.

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    ABSTRACT: A global genome database of all of Earth’s species diversity could be a treasure trove of scientific discoveries. However, regardless of the major advances in genome sequencing technologies, only a tiny fraction of species have genomic information available. To contribute to a more complete planetary genomic database, scientists and institutions across the world have united under the Earth BioGenome Project (EBP), which plans to sequence and assemble high-quality reference genomes for all ∼1.5 million recognized eukaryotic species through a stepwise phased approach. As the initiative transitions into Phase II, where 150,000 species are to be sequenced in just four years, worldwide participation in the project will be fundamental to success. As the European node of the EBP, the European Reference Genome Atlas (ERGA) seeks to implement a new decentralised, accessible, equitable and inclusive model for producing high-quality reference genomes, which will inform EBP as it scales. To embark on this mission, ERGA launched a Pilot Project to establish a network across Europe to develop and test the first infrastructure of its kind for the coordinated and distributed reference genome production on 98 European eukaryotic species from sample providers across 33 European countries. Here we outline the process and challenges faced during the development of a pilot infrastructure for the production of reference genome resources, and explore the effectiveness of this approach in terms of high-quality reference genome production, considering also equity and inclusion. The outcomes and lessons learned during this pilot provide a solid foundation for ERGA while offering key learnings to other transnational and national genomic resource projects.info:eu-repo/semantics/publishedVersio

    Biocontrol Potential of Forest Tree Endophytes

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    O31 Integrative analysis reveals a molecular stratification of systemic autoimmune diseases

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    The evolution of lung cancer and impact of subclonal selection in TRACERx

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    Lung cancer is the leading cause of cancer-associated mortality worldwide. Here we analysed 1,644 tumour regions sampled at surgery or during follow-up from the first 421 patients with non-small cell lung cancer prospectively enrolled into the TRACERx study. This project aims to decipher lung cancer evolution and address the primary study endpoint: determining the relationship between intratumour heterogeneity and clinical outcome. In lung adenocarcinoma, mutations in 22 out of 40 common cancer genes were under significant subclonal selection, including classical tumour initiators such as TP53 and KRAS. We defined evolutionary dependencies between drivers, mutational processes and whole genome doubling (WGD) events. Despite patients having a history of smoking, 8% of lung adenocarcinomas lacked evidence of tobacco-induced mutagenesis. These tumours also had similar detection rates for EGFR mutations and for RET, ROS1, ALK and MET oncogenic isoforms compared with tumours in never-smokers, which suggests that they have a similar aetiology and pathogenesis. Large subclonal expansions were associated with positive subclonal selection. Patients with tumours harbouring recent subclonal expansions, on the terminus of a phylogenetic branch, had significantly shorter disease-free survival. Subclonal WGD was detected in 19% of tumours, and 10% of tumours harboured multiple subclonal WGDs in parallel. Subclonal, but not truncal, WGD was associated with shorter disease-free survival. Copy number heterogeneity was associated with extrathoracic relapse within 1 year after surgery. These data demonstrate the importance of clonal expansion, WGD and copy number instability in determining the timing and patterns of relapse in non-small cell lung cancer and provide a comprehensive clinical cancer evolutionary data resource

    The evolution of non-small cell lung cancer metastases in TRACERx

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    Metastatic disease is responsible for the majority of cancer-related deaths. We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours. In 25% of cases, metastases diverged early, before the last clonal sweep in the primary tumour, and early divergence was enriched for patients who were smokers at the time of initial diagnosis. Simulations suggested that early metastatic divergence more frequently occurred at smaller tumour diameters (less than 8 mm). Single-region primary tumour sampling resulted in 83% of late divergence cases being misclassified as early, highlighting the importance of extensive primary tumour sampling. Polyclonal dissemination, which was associated with extrathoracic disease recurrence, was found in 32% of cases. Primary lymph node disease contributed to metastatic relapse in less than 20% of cases, representing a hallmark of metastatic potential rather than a route to subsequent recurrences/disease progression. Metastasis-seeding subclones exhibited subclonal expansions within primary tumours, probably reflecting positive selection. Our findings highlight the importance of selection in metastatic clone evolution within untreated primary tumours, the distinction between monoclonal versus polyclonal seeding in dictating site of recurrence, the limitations of current radiological screening approaches for early diverging tumours and the need to develop strategies to target metastasis-seeding subclones before relapse

    Antibodies against endogenous retroviruses promote lung cancer immunotherapy

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    B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS). Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response

    Genomic–transcriptomic evolution in lung cancer and metastasis

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    Intratumour heterogeneity (ITH) fuels lung cancer evolution, which leads to immune evasion and resistance to therapy. Here, using paired whole-exome and RNA sequencing data, we investigate intratumour transcriptomic diversity in 354 non-small cell lung cancer tumours from 347 out of the first 421 patients prospectively recruited into the TRACERx study. Analyses of 947 tumour regions, representing both primary and metastatic disease, alongside 96 tumour-adjacent normal tissue samples implicate the transcriptome as a major source of phenotypic variation. Gene expression levels and ITH relate to patterns of positive and negative selection during tumour evolution. We observe frequent copy number-independent allele-specific expression that is linked to epigenomic dysfunction. Allele-specific expression can also result in genomic–transcriptomic parallel evolution, which converges on cancer gene disruption. We extract signatures of RNA single-base substitutions and link their aetiology to the activity of the RNA-editing enzymes ADAR and APOBEC3A, thereby revealing otherwise undetected ongoing APOBEC activity in tumours. Characterizing the transcriptomes of primary–metastatic tumour pairs, we combine multiple machine-learning approaches that leverage genomic and transcriptomic variables to link metastasis-seeding potential to the evolutionary context of mutations and increased proliferation within primary tumour regions. These results highlight the interplay between the genome and transcriptome in influencing ITH, lung cancer evolution and metastasis
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