Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Anthocyanins Downregulate Lipopolysaccharide-Induced Inflammatory Responses in BV2 Microglial Cells by Suppressing the NF-κB and Akt/MAPKs Signaling Pathways

Anthocyanins are naturally occurring polyphenols that impart bright color to fruits, vegetables and plants and have a variety of protective properties, which have generally been attributed to their antioxidant capacity. However, little is known about the molecular mechanisms underlying anti-inflammatory effects of anthocyanins related to neurodegenerative diseases. Therefore, we determined whether anthocyanins isolated from black soybean seed coats would inhibit pro-inflammatory mediators and cytokines in lipopolysaccharide (LPS)-stimulated murine BV2 microglial cells. Our results showed that anthocyanins significantly inhibited LPS-induced pro-inflammatory mediators, such as nitric oxide (NO) and prostaglandin E2, and pro-inflammatory cytokines including tumor necrosis factor (TNF)-α and interleukin (IL)-1β, without significant cytotoxicity. Anthocyanins also downregulated excessive expression of inducible NO synthase, cyclooxygenase-2, TNF-α, and IL-1β in LPS-stimulated BV2 cells. Moreover, anthocyanins inhibited nuclear translocation of nuclear factor-kappa B (NF-κB) by reducing inhibitor of NF-κB alpha degradation as well as phosphorylating extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38 mitogen-activated protein kinase, and Akt. These findings suggest that anthocyanins may offer substantial therapeutic potential for treating inflammatory and neurodegenerative diseases accompanied by microglial activation

Desvelando o cotidiano dos cuidadores informais de idosos Revelando el cotidiano de los cuidadores informales de ancianos Unveiling the routine of informal caregivers for the elderly

Este artigo objetivou descrever como os cuidadores informais de idosos interpretam e constroem o seu cotidiano. Estudo qualitativo, descritivo-exploratório, tendo como orientação teórico-metodológica, a dialética. O instrumento de coleta de dados foi a entrevista individual, com cinco cuidadores de idosos dependentes em domicílios de um Programa Saúde da Família, em Montes Claros Minas Gerais. Resultados evidenciaram situações adversas enfrentadas pelos cuidadores relacionadas ao sofrimento e sacrifícios na prestação dos cuidados e a falta de assistência para atender as necessidades do ser cuidado e do ser cuidador. Porém, exercem o cuidar com amor, carinho e dedicação, utilizando a fé e a espiritualidade como busca do equilíbrio biopsicossocial. Recomenda-se que esses profissionais tenham um olhar respeitoso e cooperativo ao trabalho desses cuidadores.<br>El propósito del presente artículo ha sido describir cómo los cuidadores informales de ancianos interpretan y construyen su rutina. Se trata de un estudio cualitativo, descriptivo y exploratorio, con orientación teórico-metodológica. La recogida de datos se realizó mediante entrevistas individuales a cinco cuidadores de personas mayores dependientes que viven en domicilios incluidos en un Programa de Salud de la Familia de Montes Claros, Estado de Minas Gerais. Los resultados revelan que los cuidadores enfrentan situaciones hostiles que tienen que ver con sufrimiento y sacrificios en la prestación de los cuidados y con la falta de asistencia para atender a las necesidades del anciano y del cuidador. Pero, ejercen su tarea con amor, cariño y dedicación y, a través de la fe y de la espiritualidad, buscan su equilibrio biopsicosocial. Se aconseja que el trabajo de estos profesionales sea considerado com respecto y cooperación.<br>This article intends to describe how the informal caregivers interpret and build their daily routine. It is a qualitative study using dialectics as the theoretical-methodological framework. The instrument for data colection was individual interviews with five caregivers for elderly in homes in the Family Health Program, in Montes Claros, Minas Gerais State, Brazil. The results demonstrated adverse situations faced by caregivers in terms of suffering and sacrifice in providing care and a lack of support meeting the needs of the caregivers and those receiving care. However, they provided care with love and dedication using faith and spirituality in search of bio-psychosocial balance. It is recommended that health workers should have a respectful and cooperative approach to the work of these informal caregivers for the elderly