La influencia de la metrópolis futurista y la ciudad tecnologizada en el cine de animación japonés. Metrópolis de Rintaro como escenario de poder narrativo frenético y fascinante

Abstract: On the basis of the japanese animation model, with its consequent features and symbolisms and its cultural idiosyncrasies, a research will be carried out on the power that the city imposes on the animated film narrative. It will be approached from the perspective of a mainly qualitative analysis based on a method of studying the content of two concepts: post-apocalyptic and cybersociety in Rintaro's film Metropolis.  The city, as the main character of the story, will allow us to examine the visual, aesthetic and thematic concepts that define and constitute the film. The case study of the influence of the futuristic metropolis and the technologised city in japanese animated film subjects brings the selected feature film to a procedure of narrative and visual references that, two decades after its release, has positioned Metropolis as one of the main anime products of cinematic exploration indispensable in the advancement of popular film culture.  Resumen: A partir del modelo de animación nipón, con sus consecuentes rasgos y simbolismos y su idiosincrasia cultural, se llevará a cabo una investigación sobre el poder que la ciudad impone en la narrativa cinematográfica animada. Se abordará desde la exposición de un análisis principalmente cualitativo partiendo de un método de estudio del contenido de dos conceptos: post-apocalíptico y cibersociedad en la película Metrópolis (Metropolis, Rintaro, 2001). La ciudad, como personaje principal del relato, permitirá examinar los conceptos visuales, estéticos y temáticos que definen y constituyen el film. El estudio del caso que representa la influencia de la metrópolis futurista y la ciudad tecnologizada en el cine de animación japonés somete al largometraje seleccionado a un procedimiento de referencias narrativas y visuales que, transcurridas dos décadas desde su estreno, lo ha posicionado como uno de los principales productos anime de exploración cinematográfica indispensable en el avance de la cultura popular cinematográfica. &nbsp

La introducción de la práctica química en la Real Botica Española

The introduction of Chemist in the elaboration of medicines in the Spanish Royal Pharmacy will finally be done effective at the same time that the proclamation of King Philipe V.Los intentos de introducir la aplicación de la química en la elaboración de medicamentos en la Real Botica española se harán realidad definitivamente, coincidiendo con la llegada a la corte de Felipe V y de su equipo de sanitarios: médicos, cirujanos y boticarios

miR-28 regulates the germinal center reaction and blocks tumor growth in preclinical models of non-Hodgkin lymphoma

Non-Hodgkin lymphoma comprises a variety of neoplasms, many of which arise from germinal center (GC)-experienced B cells. microRNA-28 (miR-28) is a GC-specific miRNA whose expression is lost in numerous mature B-cell neoplasms. Here we show that miR-28 regulates the GC reaction in primary B cells by impairing class switch recombination and memory B and plasma cell differentiation. Deep quantitative proteomics combined with transcriptome analysis identified miR-28 targets involved in cell-cycle and B-cell receptor signaling. Accordingly, we found that miR-28 expression diminished proliferation in primary and lymphoma cells in vitro. Importantly, miR-28 reexpression in human Burkitt (BL) and diffuse large B-cell lymphoma (DLBCL) xenografts blocked tumor growth, both when delivered in viral vectors or as synthetic, clinically amenable, molecules. Further, the antitumoral effect of miR-28 is conserved in a primary murine in vivo model of BL. Thus, miR-28 replacement is uncovered as a novel therapeutic strategy for DLBCL and BL treatment.This work was supported by a Ministerio de Economia y Competitividad's research training program (Formacion de Personal Investigador [FPI]) fellowship (N.B.-I.); the Ramon y Cajal program (RYC-2009-04503) funded by the Ministerio de Educacion, Cultura y Deporte and the European Research Council Proof of Concept program (HEAL-BY-MIRNA 713728) (V.G.d.Y.); the Centro Nacional de Investigaciones Cardiovaculares (CNIC) (A.F.A.-P., S.M.M., A.R.R.); the Ministerio de Economia y Competitividad (SAF2010-21394, SAF2013-42767-R), the European Research Council Starting Grant program (BCLYM-207844), and Proof of Concept program (HEAL-BY-MIRNA 713728) (A.R.R.); the People Programme-Marie Curie Actions (FP7-PIIF-2012-328177), Spanish Ministry of Economy and Competitiveness (MINECO; SAF2013-45787-R), and Gobierno de Navarra (GN-106/2014) (S.R.); and the Ministerio de Economia y Competitividad (BIO2012-37926 and BIO2015-67580-P), Instituto de Salud Carlos III (Fondo de Investigacion Sanitaria [FIS] grants PRB2 [IPT13/0001, Proteo-Red], the Fundacion La Marato TV3, and Redes tematicas de investigacion cooperativa en salud [RETICS] [RD12/0042/00056, RIC]) (J.V.). This work has been cofunded by Fondo Europeo de Desarrollo Regional (FEDER) funds. The CNIC is supported by the and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (MINECO award SEV-2015-0505).S

Impact of non-invasive mechanical ventilation (niv) in critical patients with influenza (H1N1) PDM09

The use of non-invasive mechanical ventilation (NIV) in patients with influenza A (H1N1)pdm09 admitted to intensive care units (ICU) has been controversial

miR-217 is an oncogene that enhances the germinal center reaction.

microRNAs are a class of regulators of gene expression that have been shown critical for a great number of biological processes; however, little is known of their role in germinal center (GC) B cells. Although the GC reaction is crucial to ensure a competent immune response, GC B cells are also the origin of most human lymphomas, presumably due to bystander effects of the immunoglobulin gene remodeling that takes place at these sites. Here we report that miR-217 is specifically upregulated in GC B cells. Gain- and loss-of-function mouse models reveal that miR-217 is a positive modulator of the GC response that increases the generation of class-switched antibodies and the frequency of somatic hypermutation. We find that miR-217 down-regulates the expression of a DNA damage response and repair gene network and in turn stabilizes Bcl-6 expression in GC B cells. Importantly, miR-217 overexpression also promotes mature B-cell lymphomagenesis; this is physiologically relevant as we find that miR-217 is overexpressed in aggressive human B-cell lymphomas. Therefore, miR-217 provides a novel molecular link between the normal GC response and B-cell transformation.S

Aging-Associated miR-217 Aggravates Atherosclerosis and Promotes Cardiovascular Dysfunction.

microRNAs are master regulators of gene expression with essential roles in virtually all biological processes. miR-217 has been associated with aging and cellular senescence, but its role in vascular disease is not understood. Approach and Results: We have used an inducible endothelium-specific knock-in mouse model to address the role of miR-217 in vascular function and atherosclerosis. miR-217 reduced NO production and promoted endothelial dysfunction, increased blood pressure, and exacerbated atherosclerosis in proatherogenic apoE-/- mice. Moreover, increased endothelial miR-217 expression led to the development of coronary artery disease and altered left ventricular heart function, inducing diastolic and systolic dysfunction. Conversely, inhibition of endogenous vascular miR-217 in apoE-/- mice improved vascular contractility and diminished atherosclerosis. Transcriptome analysis revealed that miR-217 regulates an endothelial signaling hub and downregulates a network of eNOS (endothelial NO synthase) activators, including VEGF (vascular endothelial growth factor) and apelin receptor pathways, resulting in diminished eNOS expression. Further analysis revealed that human plasma miR-217 is a biomarker of vascular aging and cardiovascular risk. Our results highlight the therapeutic potential of miR-217 inhibitors in aging-related cardiovascular disease.V.G. de Yébenes was supported by Ramón y Cajal grant RYC-2009-04503 and AECC foundation grant INVES18013GARC and by the Universidad Complutense de Madrid. S.M. Mur and A.R. Ramiro are supported by Centro Nacional de Investigaciones Cardiovasculares (CNIC) funding. A.R. Ramiro was supported by the Spanish Ministerio de Ciencia e Innovación (PID2019-107551RB-I00), the Spanish Ministerio de Economía, Industria y Competitividad (SAF2013-42767-R and SAF2016-75511-R), and the European Research Council StG BCLYM. M. Salaices was supported by the Ministerio de Ciencia e Innovación (SAF2016-80305P) and with J. Miguel Redondo by Instituto de Salud Carlos III (CIBER de Enfermedades Cardiovasculares, CB16/11/00286 and CB16/11/00264) and Comunidad de Madrid (B2017/BMD-3676). V.G. de Yébenes was supported by Ministerio de Ciencia e Innovación (PID2019-107551RB-I00). Further support was provided by the European Social Fund and the European Regional Development Fund “A Way to Build Europe.” The CNIC is supported by Ministerio de Ciencia, Innovacion y Universidades, and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505).S

In vivo conditional deletion of HDAC7 reveals its requirement to establish proper B lymphocyte identity and development

Class IIa histone deacetylase (HDAC) subfamily members are tissue-specific gene repressors with crucial roles in development and differentiation processes. A prominent example is HDAC7, a class IIa HDAC that shows a lymphoid-specific expression pattern within the hematopoietic system. In this study, we explored its potential role in B cell development by generating a conditional knockout mouse model. Our study demonstrates for the first time that HDAC7 deletion dramatically blocks early B cell development and gives rise to a severe lymphopenia in peripheral organs, while also leading to pro-B cell lineage promiscuity. We find that HDAC7 represses myeloid and T lymphocyte genes in B cell progenitors through interaction with myocyte enhancer factor 2C (MEFC2). In B cell progenitors, HDAC7 is recruited to promoters and enhancers of target genes, and its absence leads to increased enrichment of histone active marks. Our results prove that HDAC7 is a bona fide transcriptional repressor essential for B cell development

The 8.2-event record on the Alicante marine continental shelf (SE, Spain)

High resolution seismic profiles of the Alicante continental shelf have been studied identifying a seismic prism which top at about -20 m below today sea-level. The prism is covered by recent sediments and can be interpreted as formed during a short interval of stand-by in the general transgression after the last glacial maximum. The -20 m level have been compared with the holocene Mediterranean sea-level-curve to propose an age of about 8 ka BP coinciding with the «8.2 ka cooling event» that was an abrupt, widespread climate instability. The prism top is deeper in the northern seismic profiles thus indicating a more subsidence that the southern coastal shelf where an erosion surface with rocky shoals configure the sea botto