Suchergebnisse

Squamous cell lung cancer (SCC) and adenocarcinoma are the most common histological subtypes of non-small cell lung cancer (NSCLC), and have been traditionally managed in the clinic as a single entity. Increasing evidence, however, illustrates the biological diversity of these two histological subgroups of lung cancer, and supports the need to improve our understanding of the molecular basis beyond the different phenotypes if we aim to develop more specific and individualized targeted therapy. The purpose of this study was to identify microRNA (miRNA)-dependent transcriptional regulation differences between SCC and adenocarcinoma histological lung cancer subtypes. In this work, paired miRNA (667 miRNAs by TaqMan Low Density Arrays (TLDA)) and mRNA profiling (Whole Genome 44 K array G112A, Agilent) was performed in tumor samples of 44 NSCLC patients. Nine miRNAs and 56 mRNAs were found to be differentially expressed in SCC versus adenocarcinoma samples. Eleven of these 56 mRNA were predicted as targets of the miRNAs identified to be differently expressed in these two histological conditions. Of them, 6 miRNAs (miR-149, miR-205, miR-375, miR-378, miR-422a and miR-708) and 9 target genes (CEACAM6, CGN, CLDN3, ABCC3, MLPH, ACSL5, TMEM45B, MUC1) were validated by quantitative PCR in an independent cohort of 41 lung cancer patients. Furthermore, the inverse correlation between mRNAs and microRNAs expression was also validated. These results suggest miRNA-dependent transcriptional regulation differences play an important role in determining key hallmarks of NSCLC, and may provide new biomarkers for personalized treatment strategies ; LPA is funded by Fondo de Investigación Sanitaria (PI081156, PI1102688 and R12/0036/0028), Proyecto de Excelencia de la Consejería de Innovación, Ciencia y Empresa, Junta de Andalucía (P08-CVI-04090), and the Roche Fellowship in 75th Anniversary, Spain. SMP is funded by Fondo de Investigación Sanitaria (CD1100153), Fundación Científica de la Asociación Española Contra el Cáncer, Consejería de Salud, Servicio Andaluz de Salud (PI-0224/2009 and PI-0046/2012), and Fundación Mutua Madrileña (2009). MDP is funded by Fondo de Investigación Sanitaria (CD0900148). RGC is funded by Fondo de Investigación Sanitaria (PI10/02164). GMB is funded by SAF2010-20175 and Madrid Regional Government (S2010/BMD-2303). AC lab was supported by grants to from the Spanish Ministry of Economy and Competitivity, ISCIII (PI12/00137, RTICC: RD12/0036/0028), Consejeria de Ciencia e Innovacion (CTS-6844) and Consejeria de Salud of the Junta de Andalucia (PI-0135-2010 and PI-0306-2012)

Different microRNAs (miRNAs), including miR-29 family, may play a role in the development of heart failure (HF), but the underlying molecular mechanisms in HF pathogenesis remain unclear. We aimed at characterizing mice deficient in miR-29 in order to address the functional relevance of this family of miRNAs in the cardiovascular system and its contribution to heart disease. In this work, we show that mice deficient in miR-29a/b1 develop vascular remodeling and systemic hypertension, as well as HF with preserved ejection fraction (HFpEF) characterized by myocardial fibrosis, diastolic dysfunction, and pulmonary congestion, and die prematurely. We also found evidence that the absence of miR-29 triggers the up-regulation of its target, the master metabolic regulator PGC1α, which in turn generates profound alterations in mitochondrial biogenesis, leading to a pathological accumulation of small mitochondria in mutant animals that contribute to cardiac disease. Notably, we demonstrate that systemic hypertension and HFpEF caused by miR-29 deficiency can be rescued by PGC1α haploinsufficiency, which reduces cardiac mitochondrial accumulation and extends longevity of miR-29-mutant mice. In addition, PGC1α is overexpressed in hearts from patients with HF. Collectively, our findings demonstrate the in vivo role of miR-29 in cardiovascular homeostasis and unveil a novel miR-29/PGC1α regulatory circuitry of functional relevance for cell metabolism under normal and pathological conditions. ; ERC-Advanced Grant, DeAge - European Union (grant number 742067). Received by CL-O. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Ministerio de Economı´a y Competitividad. Received by CL-O. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Instituto de Salud Carlos III. Received by CL-O. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Centro de Investigacion Biomedica en Red de Cancer CIBERONC. Received by CL-O. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Plan Feder. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Progeria Research Foundation. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The Instituto Universitario de Oncologı´a is supported by Fundacio´n Bancaria Caja de Ahorros de Asturias. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The Centro Nacional de Investigaciones Cardiovasculares (CNIC) is supported by the Ministry of Economy, Industry and Competitiveness (MINECO), and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence. (grant number SEV-2015-0505). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. APU is supported by the Human Frontier Science Program. (grant numberLT000640/2013). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. EO is supported by the 'Talent Attraction program' of Comunidad de Madrid. (grant number 2017-T1/ BMD-5185). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ; Sí

Desde antes de la confirmación pontificia de la Orden de Predicadores el 22 de diciembre de 1216, lo político ha estado presente en la vida y los quehaceres de los frailes dominicos. No obstante, esa presencia no se reduce a lo que en la Ilustración y en los siglos XIX y XX concibieron por política, es decir, la ciencia y el ejercicio concernientes al gobierno de las sociedades, sobre todo de los Estados nación, tampoco se agota en el concepto griego de polis o policía, sino que parte de dos conceptos de la tradición cristiana: el de persona, entendido como sustancia individual de naturaleza racional, y el de bien común o de todo aquello que es en beneficio de todas las personas. En este libro, fruto de la contribución de una amplia red de historiadores, se estudia la participación de los dominicos en diversas disyuntivas en las que, en tanto homo politicus, los frailes han estado enfrentados al ineludible papel de tomar partido en los procesos políticos asumidos por los grupos sociales en los que han estado presentes a lo largo y ancho del mundo. ; Since before the pontifical confirmation of the Order of Preachers on December 22, 1216, the political has been present in the life and tasks of the Dominican friars. However, that presence is not limited to what the Enlightenment and the nineteenth and twentieth centuries conceived by politics, that is, the science and exercise concerning the governance of societies, especially nation-states, is not exhausted either. in the Greek concept of polis or police, but part of two concepts of the Christian tradition: the person, understood as an individual substance of a rational nature, and the common good or all that is for the benefit of all people. In this book, fruit of the contribution of a wide network of historians, the participation of the Dominicans in diverse disjunctives is studied in which, as homo politicus, the friars have been faced with the inescapable role of taking sides in the political processes assumed by the social groups in which they have been present throughout the world.

Histone H4 acetylation at Lysine 16 (H4K16ac) is a key epigenetic mark involved in gene regulation, DNA repair and chromatin remodeling, and though it is known to be essential for embryonic development, its role during adult life is still poorly understood. Here we show that this lysine is massively hyperacetylated in peripheral neutrophils. Genome-wide mapping of H4K16ac in terminally differentiated blood cells, along with functional experiments, supported a role for this histone post-translational modification in the regulation of cell differentiation and apoptosis in the hematopoietic system. Furthermore, in neutrophils, H4K16ac was enriched at specific DNA repeats. These DNA regions presented an accessible chromatin conformation and were associated with the cleavage sites that generate the 50 kb DNA fragments during the first stages of programmed cell death. Our results thus suggest that H4K16ac plays a dual role in myeloid cells as it not only regulates differentiation and apoptosis, but it also exhibits a non-canonical structural role in poising chromatin for cleavage at an early stage of neutrophil cell death. ; Plan Nacional de I+D+I co-funding FEDER [PI15/00892 and PI18/01527 to M.F.F. and A.F.F.; PI16/01318 and PI14/01244 to C.L.]; ISCIII-Subdireccion General de Evaluacion y Fomento de la Investigacion, and Plan Nacional de I+D+I 2008–2011/FEDER [CP11/00131 to A.F.F.]; IUOPA (to G.F.B. and M.I.S.); Fundacion Cientifica de la AECC (to R.G.U.); Ministry of Economy and Competitiveness Juan de la Cierva postdoctoral fellowships [FJCI-2015-26965 to J.R.T., IJCI-2015- 23316 to V.L.]; Fundacion Ramon Areces (to M.F.F); FICYT (to E.G.T., M.G.G., A.C.); Asturias Regional Government [GRUPIN14-052 to M.F.F.]; Gobierno del Principado de Asturias, PCTI-Plan de Ciencia, Tecnologia e Innovacion co-funding Fondos FEDER (grant number IDI/2018/146 to M.F.F. and IDI/2018/144 to C.L.); Deutsche Forschungsgemeinschaft (DFG) [SFB960 to A.V.G., R.D.]; European Research Council [CoG-2014-646903]; Spanish Ministry of Economy and Competitiveness [SAF-SAF2013-43065 to P.M.]; Asociacion Española Contra el Cancer [AECC-CI-2015]; FERO Foundation, and the ISCIII [PI14-01191 to C.B.]; P.M. acknowledges financial support from The Obra Social La Caixa Fundacio Josep Carreras and The Generalitat de Catalunya (SGR330). P.M. an investigator from the Spanish Cell Therapy cooperative network (TERCEL). The IUOPA is supported by the Obra Social Liberbank-Cajastur, Spain. Funding for open access charge: Plan Nacional de I+D+I co-funding FEDER [PI18/01527].