CTCF orchestrates the germinal centre transcriptional program and prevents premature plasma cell differentiation

In germinal centres (GC) mature B cells undergo intense proliferation and immunoglobulin gene modification before they differentiate into memory B cells or long-lived plasma cells (PC). GC B-cell-to-PC transition involves a major transcriptional switch that promotes a halt in cell proliferation and the production of secreted immunoglobulins. Here we show that the CCCTC-binding factor (CTCF) is required for the GC reaction in vivo, whereas in vitro the requirement for CTCF is not universal and instead depends on the pathways used for B-cell activation. CTCF maintains the GC transcriptional programme, allows a high proliferation rate, and represses the expression of Blimp-1, the master regulator of PC differentiation. Restoration of Blimp-1 levels partially rescues the proliferation defect of CTCF-deficient B cells. Thus, our data reveal an essential function of CTCF in maintaining the GC transcriptional programme and preventing premature PC differentiation

Range extension to Santo Domingo de los Tsáchilas province and revised distribution of Platyrrhinus chocoensis (Phyllostomidae: Chiroptera) in western Ecuador

We report the first record of the Choco broad-nosed bat (Plathyrrhinus chocoensis Alberico & Velazco, 1991) in Santo Domingo de los Tsáchilas province in northwestern Ecuador. This voucher specimen represents the southernmost record of the species and expands its distribution ca. 120 km south. The animal was caught at a farm, specifically in a live fence consisting of several tree species. Preservation of bat species occurring in agricultural landscapes requires local policies and environmental education

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

CTCF orchestrates the germinal centre transcriptional program and prevents premature plasma cell differentiation

In germinal centres (GC) mature B cells undergo intense proliferation and immunoglobulin gene modification before they differentiate into memory B cells or long-lived plasma cells (PC). GC B-cell-to-PC transition involves a major transcriptional switch that promotes a halt in cell proliferation and the production of secreted immunoglobulins. Here we show that the CCCTC-binding factor (CTCF) is required for the GC reaction in vivo, whereas in vitro the requirement for CTCF is not universal and instead depends on the pathways used for B-cell activation. CTCF maintains the GC transcriptional programme, allows a high proliferation rate, and represses the expression of Blimp-1, the master regulator of PC differentiation. Restoration of Blimp-1 levels partially rescues the proliferation defect of CTCF-deficient B cells. Thus, our data reveal an essential function of CTCF in maintaining the GC transcriptional programme and preventing premature PC differentiation

HERMENÉUTICA DE LA OBSERVACIÓN MEDIANTE EVALUACIONES ESCRITAS PARA EL PLANTEAMIENTO DEL PROBLEMA DE INVESTIGACIÓN Y LA FORMULACIÓN AL PROBLEMA CIENTÍFICO

El propósito del estudio fue la hermenéutica de la observación mediante evaluaciones escritas para el planteamiento del  problema de investigación y la formulación al problema científico. El estudio se realizó durante febrero y marzo del 2020 en la Universidad Nacional ¨San Luis Gonzaga¨ Ica, Perú. Se aplicó, 15 preguntas escritas a los docentes con referencias a los módulos: 1ro) investigación científica con enfoque cualimétrico y producción intelectual, y 2do) gnoseología y epistemología: argumentos en la investigación científica. Mediante un muestreo probabilístico aleatorio se seleccionó, 10 resultados individuales calificándose de 13 puntos como valor mínimo y 20 puntos el valor máximo donde 15 puntos fue el promedio que se alcanzó. En el contraste de hipótesis, el valor de t tabulado fue -2,262 siendo menor a la t calculada (-7,67) rechazándose la hipótesis nula que, no hay dificultad en el reconocimiento del problema de investigación y el problema científico (µ≥17). El error en el planteamiento del problema de investigación fue de 60% mientras que, el 38% fue para la formulación al problema científico. Las principales razones de análisis fueron: 1ro) la no sistematicidad (objeto de investigación), 2do) examen no crítico (heurística) y; 3ro) las pocas verificaciones (comprobación de hipótesis). Finalmente, las evaluaciones escritas indicaron la inconsecuente descripción del objeto de investigación y su influencia negativa para el planteamiento del problema de investigación y la formulación al problema científico

Casas de infinitas privaciones: ¿Germen de ciudades para todos?

La presente colección Ciudades de la Gente representa a hombres y mujeres cuya cultura popular, producto de las mezclas de todos aquellos que vivían y otros que han llegado a nuestros territorios, han hecho de lugares declarados como no aptos, lugares donde vivir, y han creado dentro de nuestras ciudades, la extensión de lo distinto. Son hombres y mujeres cuyo trabajo, el que tienen para aportar, junto al de otros y otras de su misma condición, les ha permitido autoproducir interesantes y sin duda bellos espacios donde convivir. Los profesores e investigadores miembros del Grupo de Trabajo Hábitat Popular e Inclusión Social de CLACSO, nos unimos a todos aquellos hacedores que, superando los miedos y con deseos de avanzar, se atreven a caminar por lo desconocido y a no conformarse con lo conocido de otras realidades, buscando en conjunto afirmar, como derechos universales, las posibilidades de vidas dignas y de construcciones colectivas dentro de nuestras ciudades. Emprendemos la tarea de describir e interpretar el hábitat popular y la inclusión social, abriendo posibilidades para que, experimentados y debutantes líderes populares e investigadores, hablen sobre "las ciudades de la gente" de muy diversos modos

Global beta diversity patterns of microbial communities in the surface and deep ocean

This is contribution 1112 from AZTI Marine Research Division.-- 14 pages, 4 figures, 3 tables, supporting information https://doi.org/10.1111/geb.13572.-- Data Availability Statement: DNA sequences for surface prokaryotes are publicly available at the European Nucleotide Archive [http://www.ebi.ac.uk/ena; accession number PRJEB25224 (16S rRNA genes)], for deep prokaryotes at the National Center for Biotechnology Information (NCBI) Sequence Read Archive (http://www.ncbi.nlm.nih.gov/Traces/sra) under accession ID SRP031469, and for surface and deep picoeukaryotes at the European Nucleotide Archive with accession number PRJEB23771 (http://www.ebi.ac.uk/ena). Environmental data used in this study are available from https://github.com/ramalok/malaspina.surface.metabacoding, Giner et al. (2020) and Salazar et al. (2015). The code to analyze the data and produce the figures of this research is available from the corresponding author upon request.-- This is the pre-peer reviewed version of the following article: Ernesto Villarino, James R. Watson, Guillem Chust ,A. John Woodill, Benjamin Klempay, Bror Jonsson, Josep M. Gasol, Ramiro Logares, Ramon Massana, Caterina R. Giner, Guillem Salazar, X. Anton Alvarez-Salgado, Teresa S. Catala, Carlos M. Duarte, Susana Agusti, Francisco Mauro, Xabier Irigoien, Andrew D. Barton; Global beta diversity patterns of microbial communities in the surface and deep ocean; Global Ecology and Biogeography 31(11): 2323-2336 (2022), which has been published in final form at https://doi.org/10.1111/geb.13572. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived VersionsAim: Dispersal and environmental gradients shape marine microbial communities, yet the relative importance of these factors across taxa with distinct sizes and dispersal capacity in different ocean layers is unknown. Here, we report a comparative analysis of surface and deep ocean microbial beta diversity and examine how these patterns are tied to oceanic distance and environmental gradients. Location: Tropical and subtropical oceans (30°N–40°S). Time period: 2010-2011. Major taxa studied: Prokaryotes and picoeukaryotes (eukaryotes between 0.2 and 3 μm). Methods: Beta diversity was calculated from metabarcoding data on prokaryotic and picoeukaryotic microbes collected during the Malaspina expedition across the tropical and subtropical oceans. Mantel correlations were used to determine the relative contribution of environment and oceanic distance driving community beta diversity. Results: Mean community similarity across all sites for prokaryotes was 38.9% in the surface and 51.4% in the deep ocean, compared to mean similarity of 25.8 and 12.1% in the surface and deep ocean, respectively, for picoeukaryotes. Higher dispersal rates and smaller body sizes of prokaryotes relative to picoeukaryotes likely contributed to the significantly higher community similarity for prokaryotes compared with picoeukaryotes. The ecological mechanisms determining the biogeography of microbes varied across depth. In the surface ocean, the environmental differences in space were a more important factor driving microbial distribution compared with the oceanic distance, defined as the shortest path between two sites avoiding land. In the deep ocean, picoeukaryote communities were slightly more structured by the oceanic distance, while prokaryotes were shaped by the combined action of oceanic distance and environmental filtering. Main conclusions: Horizontal gradients in microbial community assembly differed across ocean depths, as did mechanisms shaping them. In the deep ocean, the oceanic distance and environment played significant roles driving microbial spatial distribution, while in the surface the influence of the environment was stronger than oceanic distanceData collection was funded by the Malaspina 2010 Circumnavigation Expedition project (Consolider-Ingenio 2010, CSD2008-00077) and cofunded by the Basque Government (Department Deputy of Agriculture, Fishing and Food Policy). We acknowledge funding from the Spanish Government through the “Severo Ochoa Center of Excelence” accreditation CEX2019-000928-S. [...] We also acknowledge H2020 Mission Atlantic project (Ref. Grant Agreement Number 862428). EV was supported by an international exchange post-doc scholarship to Scripps Institution of Oceanography and Oregon State University granted by the Education Department of the Basque GovernmentPeer reviewe

Economía y finanzas sociales: avances en la investigación

Esta obra colectiva propone un cambio de paradigma en la investigación científica, financiera y económica, cuyo centro de atención es reducir las desigualdades sociales y económicas, mejorar la sostenibilidad ambiental y la creación eficiente de valor económico. Desde un punto de vista crítico y mediante diversos enfoques teóricos, metodológicos y disciplinares, los autores analizan el esquema financiero predominante en las economías de mercado, al tiempo que abordan temas como la inclusión financiera, la banca ética o las experiencias e intervenciones en y sobre la economía social.ITESO, A.C

Artificial intelligence within the interplay between natural and artificial computation:Advances in data science, trends and applications

Artificial intelligence and all its supporting tools, e.g. machine and deep learning in computational intelligence-based systems, are rebuilding our society (economy, education, life-style, etc.) and promising a new era for the social welfare state. In this paper we summarize recent advances in data science and artificial intelligence within the interplay between natural and artificial computation. A review of recent works published in the latter field and the state the art are summarized in a comprehensive and self-contained way to provide a baseline framework for the international community in artificial intelligence. Moreover, this paper aims to provide a complete analysis and some relevant discussions of the current trends and insights within several theoretical and application fields covered in the essay, from theoretical models in artificial intelligence and machine learning to the most prospective applications in robotics, neuroscience, brain computer interfaces, medicine and society, in general.BMS - Pfizer(U01 AG024904). Spanish Ministry of Science, projects: TIN2017-85827-P, RTI2018-098913-B-I00, PSI2015-65848-R, PGC2018-098813-B-C31, PGC2018-098813-B-C32, RTI2018-101114-B-I, TIN2017-90135-R, RTI2018-098743-B-I00 and RTI2018-094645-B-I00; the FPU program (FPU15/06512, FPU17/04154) and Juan de la Cierva (FJCI-2017–33022). Autonomous Government of Andalusia (Spain) projects: UMA18-FEDERJA-084. Consellería de Cultura, Educación e Ordenación Universitaria of Galicia: ED431C2017/12, accreditation 2016–2019, ED431G/08, ED431C2018/29, Comunidad de Madrid, Y2018/EMT-5062 and grant ED431F2018/02. PPMI – a public – private partnership – is funded by The Michael J. Fox Foundation for Parkinson’s Research and funding partners, including Abbott, Biogen Idec, F. Hoffman-La Roche Ltd., GE Healthcare, Genentech and Pfizer Inc

Assessment of a New ROS1 Immunohistochemistry Clone (SP384) for the Identification of ROS1 Rearrangements in Patients with Non–Small Cell Lung Carcinoma: the ROSING Study

Introduction: The ROS1 gene rearrangement has become an important biomarker in NSCLC. The College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology testing guidelines support the use of ROS1 immunohistochemistry (IHC) as a screening test, followed by confirmation with fluorescence in situ hybridization (FISH) or a molecular test in all positive results. We have evaluated a novel anti-ROS1 IHC antibody (SP384) in a large multicenter series to obtain real-world data. Methods: A total of 43 ROS1 FISH-positive and 193 ROS1 FISH-negative NSCLC samples were studied. All specimens were screened by using two antibodies (clone D4D6 from Cell Signaling Technology and clone SP384 from Ventana Medical Systems), and the different interpretation criteria were compared with break-apart FISH (Vysis). FISH-positive samples were also analyzed with next-generation sequencing (Oncomine Dx Target Test Panel, Thermo Fisher Scientific). Results: An H-score of 150 or higher or the presence of at least 70% of tumor cells with an intensity of staining of 2+ or higher by the SP384 clone was the optimal cutoff value (both with 93% sensitivity and 100% specificity). The D4D6 clone showed similar results, with an H-score of at least 100 (91% sensitivity and 100% specificity). ROS1 expression in normal lung was more frequent with use of the SP384 clone (p < 0.0001). The ezrin gene (EZR)-ROS1 variant was associated with membranous staining and an isolated green signal FISH pattern (p = 0.001 and p = 0.017, respectively). Conclusions: The new SP384 ROS1 IHC clone showed excellent sensitivity without compromising specificity, so it is another excellent analytical option for the proposed testing algorithm