DNMT1-interacting RNAs block gene specific DNA methylation

Summary DNA methylation was described almost a century ago. However, the rules governing its establishment and maintenance remain elusive. Here, we present data demonstrating that active transcription regulates levels of genomic methylation. We identified a novel RNA arising from the CEBPA gene locus critical in regulating the local DNA methylation profile. This RNA binds to DNMT1 and prevents CEBPA gene locus methylation. Deep sequencing of transcripts associated with DNMT1 combined with genome-scale methylation and expression profiling extended the generality of this finding to numerous gene loci. Collectively, these results delineate the nature of DNMT1-RNA interactions and suggest strategies for gene selective demethylation of therapeutic targets in disease

Reseñas de libros

[EN] García Bueno, Antonio. Dibujando la Alhambra y su Entorno (por Antonio J. Gómez-Blanco Pontes) pp. 4.-- Pozo, José M.; García-Diego, Hector y García, Izaskun ( por Carlos Montes Serrano) pp. 5.-- Laura Carlevaris, Mónica Filippa (coordinadoras)(por Antonio Álvaro Tordesillas) pp. 5 y 6.-- Esteve Secall, Carlos E. La ciencia gnomónica en la España del siglo de Oro (por Joaquín Casado de Amezúa Vázquez ) pp. 6 y 7.-- Franco Taboada, José Antonio. Geometría descriptiva para la representación arquitectónica (por Lluís Villanueva Bartrina) pp. 7 y 8.--Raposo Grau, Javier Fco; Butragueño Díaz-Guerra y Paredes Maldonado, Miguel. La ciudad como espacio de relaciones dinámicas (por Margarita de Luxán García de Diego) pp. 8 y 9.-- Castellanos Gómez, Raúl. Plan Poché (por Daniel García-Escudero) pp. 9 y 10.-- Gutiérrez Mozo, María Alia; Castilla Pascual, Francisco Javier y Real Tomás, María del Carmen. 70 años de arquitectura en Albacete: 1936-2006 ( por Javier Poyatos Sebastián) pp. 10 y 11.-- García Sánchez, María Teresa. De la ciudad en vibración al ser resonante: una investigación a propósito de los conciertos de campanas de Llorenç Barber ( por Fernando Ochoa Gómez) pp. 11.-- Pernas Alonso, Inés. Escaleras de piedra en los conjuntos monásticos de la provincia de Ourense entre los siglos xVI y xVIII. Análisis gráfico (por José Antonio Franco Taboada) pp. 12 y 13.-- Rodríguez Moreno, Dª Concepción. El palacio de Pedro I en los Reales Alcázares de Sevilla: estudio y análisis (por Joaquín Casado de Amezúa) pp. 13 y 14.—Jeremías, Pablo y Gutierrez, Juan. Tiempo de arquitectura ( por Carlos L. Marcos) pp. 14 y 15.-- Domingo Gresa, Jorge. El dibujo de arquitectura en la formación de la ciudad de Alicante: Fondo Documental del Archivo Municipal (1691-1860)(por Gaspar Jaén i Urbàn)pp.15.-- García-Solera, Javier. Dibujos y palabras en la habitación tranquila (por Gaspar Jaen) pp. 16 y 17.—Anne Griswold Tyng (1920-2011)( por Noelia Galván Desvaux)pp. 18 y 19 .-- Oscar Niemeyer Un adiós al último maestro del siglo XX(por Noelia Galván Desvaux)pp. 20 y 21Gómez-Blanco Pontes, AJ.; Montes Serrano, C.; Tordesillas, AÁ.; Casado De Amezúa Vázquez, J.; Villanueva Bartrina, L.; De Luxán García De Diego, M.; García-Escudero, D.... (2013). Reseñas de libros. EGA. Revista de Expresión Gráfica Arquitectónica. 18(21):4-21. https://doi.org/10.4995/ega.2013.1708SWORD421182

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Preclinical and randomized phase I studies of plitidepsin in adults hospitalized with COVID-19

Plitidepsin, a marine-derived cyclic-peptide, inhibits SARS-CoV-2 replication at nanomolar concentrations by targeting the host protein eukaryotic translation elongation factor 1A. Here, we show that plitidepsin distributes preferentially to lung over plasma, with similar potency against across several SARS-CoV-2 variants in preclinical studies. Simultaneously, in this randomized, parallel, open-label, proof-of-concept study (NCT04382066) conducted in 10 Spanish hospitals between May and November 2020, 46 adult hospitalized patients with confirmed SARS-CoV-2 infection received either 1.5 mg (n = 15), 2.0 mg (n = 16), or 2.5 mg (n = 15) plitidepsin once daily for 3 d. The primary objective was safety; viral load kinetics, mortality, need for increased respiratory support, and dose selection were secondary end points. One patient withdrew consent before starting procedures; 45 initiated treatment; one withdrew because of hypersensitivity. Two Grade 3 treatment-related adverse events were observed (hypersensitivity and diarrhea). Treatment-related adverse events affecting more than 5% of patients were nausea (42.2%), vomiting (15.6%), and diarrhea (6.7%). Mean viral load reductions from baseline were 1.35, 2.35, 3.25, and 3.85 log10 at days 4, 7, 15, and 31. Nonmechanical invasive ventilation was required in 8 of 44 evaluable patients (16.0%); six patients required intensive care support (13.6%), and three patients (6.7%) died (COVID-19-related). Plitidepsin has a favorable safety profile in patients with COVID-19.This work was supported by grants from the Government of Spain (PIE_INTRAMURAL_ LINEA 1 - 202020E079; PIE_INTRAMURAL_CSIC-202020E043). The research of CBIG consortium (constituted by IRTA-CReSA, BSC, & IrsiCaixa) is supported by Grifols pharmaceutical. We also acknowledge the crowdfunding initiative #Yomecorono (https://www.yomecorono.com). N Izquierdo-Useros has nonrestrictive funding from PharmaMar to study the antiviral effect of Plitidepsin. NJ Krogan was funded by grants from the National Institutes of Health (P50AI150476, U19AI135990, U19AI135972, R01AI143292, R01AI120694, and P01AI063302); by the Excellence in Research Award (ERA) from the Laboratory for Genomics Research (LGR), a collaboration between the University of California, San Francisco (UCSF), University of California, Berkley (UCB), and GlaxoSmithKline (GSK) (#133122P); by the Roddenberry Foundation, and gifts from QCRG philanthropic donors. This work was supported by the Defense Advanced Research Projects Agency (DARPA) under Cooperative Agreement #HR0011-19-2-0020. The views, opinions, and/or findings contained in this material are those of the authors and should not be interpreted as representing the official views or policies of the Department of Defense or the U.S. Government. This research was partly funded by Center for Research for Influenza Pathogenesis and Transmission (CRIPT), a National Institute of Allergy and Infectious Diseases (NIAID) supported Center of Excellence for Influenza Research and Response (CEIRS, contract # 75N93021C00014), by DARPA grant HR0011-19-2-0020, by supplements to NIAID grants U19AI142733, U19AI135972, and DoD grant W81XWH-20-1-0270, and by the generous support of the JPB Foundation, the Open Philanthropy Project (research grant 2020-215611 (5384)), and anonymous donors to A García-Sastre. S Yildiz received funding from a Swiss National Foundation Early Postdoc Mobility fellowship (P2GEP3_184202).Peer reviewe

The Amazon Tall Tower Observatory (ATTO): Overview of pilot measurements on ecosystem ecology, meteorology, trace gases, and aerosols

The Amazon Basin plays key roles in the carbon and water cycles, climate change, atmospheric chemistry, and biodiversity. It has already been changed significantly by human activities, and more pervasive change is expected to occur in the coming decades. It is therefore essential to establish long-term measurement sites that provide a baseline record of present-day climatic, biogeochemical, and atmospheric conditions and that will be operated over coming decades to monitor change in the Amazon region, as human perturbations increase in the future. The Amazon Tall Tower Observatory (ATTO) has been set up in a pristine rain forest region in the central Amazon Basin, about 150 km northeast of the city of Manaus. Two 80 m towers have been operated at the site since 2012, and a 325 m tower is nearing completion in mid-2015. An ecological survey including a biodiversity assessment has been conducted in the forest region surrounding the site. Measurements of micrometeorological and atmospheric chemical variables were initiated in 2012, and their range has continued to broaden over the last few years. The meteorological and micrometeorological measurements include temperature and wind profiles, precipitation, water and energy fluxes, turbulence components, soil temperature profiles and soil heat fluxes, radiation fluxes, and visibility. A tree has been instrumented to measure stem profiles of temperature, light intensity, and water content in cryptogamic covers. The trace gas measurements comprise continuous monitoring of carbon dioxide, carbon monoxide, methane, and ozone at five to eight different heights, complemented by a variety of additional species measured during intensive campaigns (e.g., VOC, NO, NO2, and OH reactivity). Aerosol optical, microphysical, and chemical measurements are being made above the canopy as well as in the canopy space. They include aerosol light scattering and absorption, fluorescence, number and volume size distributions, chemical composition, cloud condensation nuclei (CCN) concentrations, and hygroscopicity. In this paper, we discuss the scientific context of the ATTO observatory and present an overview of results from ecological, meteorological, and chemical pilot studies at the ATTO site. © Author(s) 2015