50 research outputs found

    Epigenetic loss of RNA-methyltransferase NSUN5 in glioma targets ribosomes to drive a stress adaptive translational program

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    Altres ajuts: This work was supported by the Obra Social "La Caixa" (to M. Esteller).Tumors have aberrant proteomes that often do not match their corresponding transcriptome profiles. One possible cause of this discrepancy is the existence of aberrant RNA modification landscapes in the so-called epitranscriptome. Here, we report that human glioma cells undergo DNA methylation-associated epigenetic silencing of NSUN5, a candidate RNA methyltransferase for 5-methylcytosine. In this setting, NSUN5 exhibits tumor-suppressor characteristics in vivo glioma models. We also found that NSUN5 loss generates an unmethylated status at the C3782 position of 28S rRNA that drives an overall depletion of protein synthesis, and leads to the emergence of an adaptive translational program for survival under conditions of cellular stress. Interestingly, NSUN5 epigenetic inactivation also renders these gliomas sensitive to bioactivatable substrates of the stress-related enzyme NQO1. Most importantly, NSUN5 epigenetic inactivation is a hallmark of glioma patients with long-term survival for this otherwise devastating disease

    Observation of inverse Compton emission from a long γ-ray burst.

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    Long-duration γ-ray bursts (GRBs) originate from ultra-relativistic jets launched from the collapsing cores of dying massive stars. They are characterized by an initial phase of bright and highly variable radiation in the kiloelectronvolt-to-megaelectronvolt band, which is probably produced within the jet and lasts from milliseconds to minutes, known as the prompt emission1,2. Subsequently, the interaction of the jet with the surrounding medium generates shock waves that are responsible for the afterglow emission, which lasts from days to months and occurs over a broad energy range from the radio to the gigaelectronvolt bands1-6. The afterglow emission is generally well explained as synchrotron radiation emitted by electrons accelerated by the external shock7-9. Recently, intense long-lasting emission between 0.2 and 1 teraelectronvolts was observed from GRB 190114C10,11. Here we report multi-frequency observations of GRB 190114C, and study the evolution in time of the GRB emission across 17 orders of magnitude in energy, from 5 × 10-6 to 1012 electronvolts. We find that the broadband spectral energy distribution is double-peaked, with the teraelectronvolt emission constituting a distinct spectral component with power comparable to the synchrotron component. This component is associated with the afterglow and is satisfactorily explained by inverse Compton up-scattering of synchrotron photons by high-energy electrons. We find that the conditions required to account for the observed teraelectronvolt component are typical for GRBs, supporting the possibility that inverse Compton emission is commonly produced in GRBs

    Benthic estuarine communities in Brazil: moving forward to long term studies to assess climate change impacts

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    Abstract Estuaries are unique coastal ecosystems that sustain and provide essential ecological services for mankind. Estuarine ecosystems include a variety of habitats with their own sediment-fauna dynamics, all of them globally undergoing alteration or threatened by human activities. Mangrove forests, saltmarshes, tidal flats and other confined estuarine systems are under increasing stress due to human activities leading to habitat and species loss. Combined changes in estuarine hydromorphology and in climate pose severe threats to estuarine ecosystems on a global scale. The ReBentos network is the first integrated attempt in Brazil to monitor estuarine changes in the long term to detect and assess the effects of global warming. This paper is an initial effort of ReBentos to review current knowledge on benthic estuarine ecology in Brazil. We herein present and synthesize all published work on Brazilian estuaries that has focused on the description of benthic communities and related ecological processes. We then use current data on Brazilian estuaries and present recommendations for future studies to address climate change effects, suggesting trends for possible future research and stressing the need for long-term datasets and international partnerships

    Estudo etnofarmacológico e etnobotânico de Himatanthus drasticus (Mart.) Plumel (janaguba)

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    RESUMO Himatanthus drasticus (Mart.) Plumel, janaguba, produz um látex em seu caule que é usado para o tratamento de alguns tipos de câncer, vermes intestinais, febre, menstruações irregulares, infertilidade feminina e úlceras gástricas. Estudos fitoquímicos revelaram a presença de acetato de lupeol e proteínas; e estudos farmacológicos, os efeitos antiúlcera, antitumoral, imunomodulador, analgésico e anti-inflamatório. O presente trabalho objetivou realizar levantamento etnobotânico e etnofarmacológico sobre H. drasticus como contribuição ao conhecimento científico da referida espécie. Foi elaborado um questionário, que foi aplicado em entrevista a 21 raizeiros nos mercados das cidades de Crato, Fortaleza e Pacajus do estado do Ceará (CE). Observou-se que 38,1% dos raizeiros têm mais de 10 anos de serviço e 47,6%, estão na faixa etária de 40 a 59 anos, o que representa um fator positivo quanto à experiência com plantas medicinais. Aproximadamente 85,7% dos raizeiros relataram o uso do látex da H. drasticus para tratamento de úlcera; 66,7% para inflamação; 66,7% para câncer. Verificou-se que as principais indicações terapêuticas relatadas pelos raizeiros sobre esta espécie estão de acordo com as informações científicas. Os levantamentos etnobotânicos e etnofarmacológicos exercem um papel primordial no resgate do conhecimento tradicional, nos meios rurais e urbanos, tanto por seu valor histórico-cultural, como também pela necessidade de confirmação das indicações de uso
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