Resultados de investigación

Here, we use single cell sequencing to delineate the heterogeneity of tumours from the genetically engineered MMTV-PyMT mouse model of breast cancer (MMTV-PyMT::K14Cre::Rosa-tdTomato mice) upon Prrx1 knock out (both heterozygous and homozygous), Disseminated cancer cells rarely succeed in forming macrometastases, yet they continue to be the most life-threatening cause of patient mortality. The determinants driving metastatic competence, however, are still poorly understood. Using data from human breast cancer patients and genetic mouse models, we uncover a non-linear relationship between the expression of the EMT transcription factor Prrx1 in the primary tumor and metastatic outcome. Multi-omics analyses in mouse tumors reveal that Prrx1 functions as a dual regulator, promoting invasive behavior while simultaneously inducing dormancy. Cells with intermediate Prrx1 levels exhibit the highest metastatic fitness, whereas extreme levels (negative or too high) lead to less metastasis, typical of a hormetic behavior, and respectively due to insufficient invasiveness or to dormancy. These findings provide mechanistic insight into the regulation of dormancy and its link to metastatic potential. Additionally, we propose that combined signatures of invasion and proliferation allow robust prognosis prediction in breast cancer patients. Our study further highlights Prrx1-driven heterogeneity, established in the primary tumor, as a key determinant of metastatic competence., Peer reviewed

Experiment type: Genome binding/occupancy profiling by high throughput sequencing. -- Here, we use single cell sequencing to delineate the chromatin heterogeneity of tumours from the genetically engineered MMTV-PyMT mouse model of breast cancer (MMTV-PyMT::K14Cre::Rosa-tdTomato mice), Disseminated cancer cells rarely succeed in forming macrometastases, yet they continue to be the most life-threatening cause of patient mortality. The determinants driving metastatic competence, however, are still poorly understood. Using data from human breast cancer patients and genetic mouse models, we uncover a non-linear relationship between the expression of the EMT transcription factor Prrx1 in the primary tumor and metastatic outcome. Multi-omics analyses in mouse tumors reveal that Prrx1 functions as a dual regulator, promoting invasive behavior while simultaneously inducing dormancy. Cells with intermediate Prrx1 levels exhibit the highest metastatic fitness, whereas extreme levels (negative or too high) lead to less metastasis, typical of a hormetic behavior, and respectively due to insufficient invasiveness or to dormancy. These findings provide mechanistic insight into the regulation of dormancy and its link to metastatic potential. Additionally, we propose that combined signatures of invasion and proliferation allow robust prognosis prediction in breast cancer patients. Our study further highlights Prrx1-driven heterogeneity, established in the primary tumor, as a key determinant of metastatic competence., Peer reviewed

Acute myeloid leukemia (AML) is a disease with poor outcome but patients harbouring certain chromosomal rearrangements or complex karyotypes have particularly adverse prognosis. For these patients, targeted therapies have not yet made a significant clinical impact. To understand the molecular landscape of poor risk AML we profiled 55 poor risk AML patients using a multiomics approach that included transcriptomics (n=39), proteomics (n=55), phosphoproteomics (n=55) and an ex vivo drug sensitivity screening (482 compounds tested in at least 30 patients). We identified a phosphoproteomics signature that define two biologically distinct groups of KMT2A rearranged leukaemia, which we term MLLGA and MLLGB. MLLGA presented increased DOT1L phosphorylation, HOXA gene expression, CDK1 activity and phosphorylation of proteins involved in RNA metabolism, replication and DNA damage when compared to MLLGB and no KMT2A rearranged samples. MLLGA was particularly sensitive to 15 compounds including genotoxic drugs and inhibitors of mitotic kinases and IMPDH relative to other cases. The expression of IMPDH2 and multiple nucleolar proteins was higher in MLLGA and correlated with the response to IMPDH inhibition in KMT2A rearranged leukaemia, suggesting a role of the nucleolar activity in sensitivity to IMPDH inhibition. In summary, our multilayer molecular profiling of poor risk AML matched to the response to hundreds of compounds identified a phosphoproteomics signature that define two biologically and phenotypically distinct groups of KMT2A rearranged leukaemia. These data provide a rationale for the development of specific therapies for KMT2A subgroups characterised by the MLLGA phosphoproteomics signature identified in this study., El dataset se puede consultar y descargar en el siguiente enlace: https://dx.doi.org/10.6019/PXD032980, The raw mass spectrometry proteomics, phosphoproteomics, mRNA sequencing, DNA sequencing data and associated clinical data generated during this study are available for non-commercial research purposes only, through an Attribution CC-BY-NC-ND license (Anyone can share this material, provided it remains unaltered in any way, this is not done for commercial purposes, and the original authors are credited and cited). Access to additional clinical data and omics data can granted upon review of a project proposal that will be evaluated by a data access committee and entering into an appropriate data access agreement subject to any applicable ethical approvals. The raw mass spectrometry phosphoproteomics data generated during this study have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository (https://www.ebi.ac.uk/pride/), Peer reviewed

Acute myeloid leukemia (AML) is a disease with poor outcome but patients harbouring certain chromosomal rearrangements or complex karyotypes have particularly adverse prognosis. For these patients, targeted therapies have not yet made a significant clinical impact. To understand the molecular landscape of poor risk AML we profiled 55 poor risk AML patients using a multiomics approach that included transcriptomics (n=39), proteomics (n=55), phosphoproteomics (n=55) and an ex vivo drug sensitivity screening (482 compounds tested in at least 30 patients). We identified a phosphoproteomics signature that define two biologically distinct groups of KMT2A rearranged leukaemia, which we term MLLGA and MLLGB. MLLGA presented increased DOT1L phosphorylation, HOXA gene expression, CDK1 activity and phosphorylation of proteins involved in RNA metabolism, replication and DNA damage when compared to MLLGB and no KMT2A rearranged samples. MLLGA was particularly sensitive to 15 compounds including genotoxic drugs and inhibitors of mitotic kinases and IMPDH relative to other cases. The expression of IMPDH2 and multiple nucleolar proteins was higher in MLLGA and correlated with the response to IMPDH inhibition in KMT2A rearranged leukaemia, suggesting a role of the nucleolar activity in sensitivity to IMPDH inhibition. In summary, our multilayer molecular profiling of poor risk AML matched to the response to hundreds of compounds identified a phosphoproteomics signature that define two biologically and phenotypically distinct groups of KMT2A rearranged leukaemia. These data provide a rationale for the development of specific therapies for KMT2A subgroups characterised by the MLLGA phosphoproteomics signature identified in this study., The raw mass spectrometry proteomics, phosphoproteomics, mRNA sequencing, DNA sequencing data and associated clinical data generated during this study are available for non-commercial research purposes only, through an Attribution CC-BY-NC-ND license (Anyone can share this material, provided it remains unaltered in any way, this is not done for commercial purposes, and the original authors are credited and cited). Access to additional clinical data and omics data can granted upon review of a project proposal that will be evaluated by a data access committee and entering into an appropriate data access agreement subject to any applicable ethical approvals. The raw mass spectrometry phosphoproteomics data generated during this study have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository (https://www.ebi.ac.uk/pride/), El dataset se puede consultar y descargar en el siguiente enlace: https://www.ebi.ac.uk/pride/archive/projects/PXD038980, Peer reviewed

Este ítem trata de la excavación de la Cabaña ceremonial yámana de Puerto Remolino en la costa norte del Canal Beagle. En él hemos incluido la Memoria escrita, que explica el sistema de localización, excavación y registro así como las conclusiones a las que llegamos, una presentación powerpoint con un resumen ilustrado del proceso, 3 álbumes con fotografías de una selección de materiales de fauna, líticos y de vidrio y cerámica (realizadas por la técnica de la UAB Selina Delgado), 3 álbumes con fotografías históricas, de la ubicación y de la excavación y la base de datos con los análisis de los materiales recuperados., Memoria donde se describe el trabajo desarrollado en el yacimiento yamana Cabaña Remolino, fotografías y una base de datos analítica., Agencias financiadoras: CSIC, CONICET, Ministerio de Educación y Ciencia (España) y Universidad de Barcelona (España)., Sí

Este ítem recoge los documentos fruto de la excavación de un enterramiento de una mujer joven en el yacimiento de Mischiwen III en la costa norte del Canal Beagle. Corresponde a la época moderna de contacto con europeos. Se excavó ensayando un método de excavación con registro de posicionales digital, fotografiado y reconstitución fotogramétrica que se explica en los textos descriptivos adjuntos. También se incluyen álbumes de fotografías de la excavación y de los materiales recuperados, tanto antropobiológicos como de artefactos líticos, los inventarios y los informes analíticos arqueobiológicos y de la datación radiocarbónica., Resultados de la excavación de un contexto mortuorio yamana en el yacimiento Mischiwen III en la costa norte del Canal Beagle. Se presentan las fotografías y los datos analíticos obtenidos., Agencias financiadoras: CSIC, CONICET, Ministerio de Educación y Ciencia (España) y Universidad de Barcelona (España)., Sí

Centro Oceanográfico de Murcia. Instituto Español de Oceanografía. Comunidad Autónoma de la Región de Murcia. Consejería de Agricultura y Agua. Dirección General de Ganadería y Pesca. Servicio de Pesca y Agricultura. Fondo Europeo de la Pesca. CE

El texto completo del artículo en el que se han utilizado estos datos se ha publicado en la revista Economic History Review 67.3 (2014): 607-626 y está disponbile en http://dx.doi.org/10.1111/1468-0289.12047, The dataset that supports the findings of this study are archived in the Universidad Autónoma de Madrid data repository e‐cienciaDatos in https://doi.org/10.21950/5SCIIO, Datos de investigación generados por José Ignacio Andrés Ucendo (Universidad del País Vasco) y Ramón Lanza García (Universidad Autónoma de Madrid) y utilizados en la elaboración del artículo "Prices and real wages in seventeeth-century in Madrid" que se ha publicado en la revista Economic Historic Review 67.3 (2014): 607-626, Research data compiled by José Ignacio Ucendo (Universidad del País Vasco) and Ramón Lanza García (Universidad Autónoma de Madrid) and used in the article "Prices and real wages in seventeeth-century in Madrid". This article is published by the Economic History Review 67.3 (2014): 607-626, Funding for the research was provided by the Spanish Economy Ministry through the projects ‘Ciudades, gentes e intercambios en la Monarquía Hispánica: política económica, cambio institucional y desarrollo de los mercados en la Edad Moderna’ (HAR2012-39034-C03-02) and ‘Consumo, niveles de vida y desigualdad en España, 1400–1870’ (HAR 2012-35965)

Peer Reviewed

Peer reviewed, Fecha 2014-09-02.--Fujitsu ScanSnap iX500.--Unidad técnica IHMC.--Archivo depósito IHMC.--Solo se permite el uso con fines educativos y de investigación