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

SGF-quantales and their groupoids

Engineering, Systems and ServicesTechnology, Policy and Managemen

Colorimetric sensing of copper(II) based on catalytic etching of gold nanorods

In this work, a sensitive colorimetric method for determination of copper(II) in aqueous solution was developed based on catalytic etching of gold nanorods (GNRs). CTAB stabilized GNRs were etched slowly by dissolved oxygen along the axial direction in NH3-NH4Cl (0.8/0.1 M) solution. The etching was accelerated by the addition of Cu2+ with very low concentration, leading to a dramatic decrease of the GNRs in length but little in diameter. The etching caused the longitudinal surface plasmon resonance (LSPR) absorption to decrease sharply and shift to the short-wave direction, accompanied by a color change from blue to slight red. Potential effects of relevant experimental conditions, including concentrations of NH3 and S2O32-, and incubation temperature and time were evaluated for optimization of the method. The proposed method is sensitive (LOD = 2.7 nM) and selective (by at least 100-fold over other metal ions except for Mn2+ and Pb2+) with a linear range from 7 to 50 nM. Furthermore, the cost-effective method allows rapid and simple determination of the content of copper in shellfish samples.In this work, a sensitive colorimetric method for determination of copper(II) in aqueous solution was developed based on catalytic etching of gold nanorods (GNRs). CTAB stabilized GNRs were etched slowly by dissolved oxygen along the axial direction in NH3-NH4Cl (0.8/0.1 M) solution. The etching was accelerated by the addition of Cu2+ with very low concentration, leading to a dramatic decrease of the GNRs in length but little in diameter. The etching caused the longitudinal surface plasmon resonance (LSPR) absorption to decrease sharply and shift to the short-wave direction, accompanied by a color change from blue to slight red. Potential effects of relevant experimental conditions, including concentrations of NH3 and S2O32-, and incubation temperature and time were evaluated for optimization of the method. The proposed method is sensitive (LOD = 2.7 nM) and selective (by at least 100-fold over other metal ions except for Mn2+ and Pb2+) with a linear range from 7 to 50 nM. Furthermore, the cost-effective method allows rapid and simple determination of the content of copper in shellfish samples

DEGRADATION OF POLLUTANTS BY HYDROPHOBIC FePcCl16 UNDER ULTRAVIOLET AND VISIBLE LIGHT

Metal complex perchlorinated iron-phthalocyanine (FePcCl16) was prepared and used as a photocatalyst. The heterogeneous photocatalytic degradation of rhodamine B (RhB) and salicylic acid (SA) by FePcCl16 activated by molecular oxygen (O-2) under ultraviolet light (lambda <= 387 nm) and by hydrogen peroxide (H2O2) under visible light irradiation (lambda >= 420 nm) were studied. The experimental results indicated that organic pollutants can be effectively degraded under both ultraviolet and visible light. Under ultraviolet and visible light illumination, the removal rates of total organic carbon (TOC) for RhB reached 86.24% after 180 min and 64.73% after 300 min, respectively. The degradation process was predominated by the hydroxyl radical (center dot OH), according to the results from benzoic acid fluorescence method. The hydrophobic photocatalyst FePcCl16 was stable in aqueous solution. The photocatalytic degradation system had wide pH adaptability (3-11). The heterogeneous photocatalyst can be reused to degrade toxic organic pollutants both under ultraviolet and visible light.Metal complex perchlorinated iron-phthalocyanine (FePcCl16) was prepared and used as a photocatalyst. The heterogeneous photocatalytic degradation of rhodamine B (RhB) and salicylic acid (SA) by FePcCl16 activated by molecular oxygen (O-2) under ultraviolet light (lambda = 420 nm) were studied. The experimental results indicated that organic pollutants can be effectively degraded under both ultraviolet and visible light. Under ultraviolet and visible light illumination, the removal rates of total organic carbon (TOC) for RhB reached 86.24% after 180 min and 64.73% after 300 min, respectively. The degradation process was predominated by the hydroxyl radical (center dot OH), according to the results from benzoic acid fluorescence method. The hydrophobic photocatalyst FePcCl16 was stable in aqueous solution. The photocatalytic degradation system had wide pH adaptability (3-11). The heterogeneous photocatalyst can be reused to degrade toxic organic pollutants both under ultraviolet and visible light

Kinetic modeling of antimony(V) adsorption-desorption and transport in soils

Antimonate [Sb(V)] adsorption-desorption and transport in an acidic red soil (Yingtan) and a calcareous soil (Huanjiang) was investigated using kinetic batch and miscible displacement experiments. Different formulations of a multi-reaction model (MRM) were evaluated for their capabilities of describing the retention and transport mechanisms of Sb(V) in soils. The experimental results showed that adsorption of Sb(V) by two soils was kinetically controlled and largely irreversible. The Sb(V) adsorption capacity and kinetic rate of the acidic red soil was much higher than that of the calcareous soil. The asymmetrical breakthrough curves indicated the strong dominance of non-equilibrium retention of Sb(V). A four step sequential extraction procedure provided evidence that majority of applied Sb(V) was irreversibly retained. A formulation of MRM with two kinetic sorption sites (reversible and irreversible) successfully described Sb(V) adsorption-desorption data. The use of kinetic batch rate coefficients for predictions of breakthrough curves (BTCs) underestimated Sb(V) retention and overestimated its mobility. In an inverse mode with optimized rate coefficients, the MRM formulation was capable of simulating Sb(V) transport in soil columns. (C) 2014 Elsevier Ltd. All rights reserved.Antimonate [Sb(V)] adsorption-desorption and transport in an acidic red soil (Yingtan) and a calcareous soil (Huanjiang) was investigated using kinetic batch and miscible displacement experiments. Different formulations of a multi-reaction model (MRM) were evaluated for their capabilities of describing the retention and transport mechanisms of Sb(V) in soils. The experimental results showed that adsorption of Sb(V) by two soils was kinetically controlled and largely irreversible. The Sb(V) adsorption capacity and kinetic rate of the acidic red soil was much higher than that of the calcareous soil. The asymmetrical breakthrough curves indicated the strong dominance of non-equilibrium retention of Sb(V). A four step sequential extraction procedure provided evidence that majority of applied Sb(V) was irreversibly retained. A formulation of MRM with two kinetic sorption sites (reversible and irreversible) successfully described Sb(V) adsorption-desorption data. The use of kinetic batch rate coefficients for predictions of breakthrough curves (BTCs) underestimated Sb(V) retention and overestimated its mobility. In an inverse mode with optimized rate coefficients, the MRM formulation was capable of simulating Sb(V) transport in soil columns. (C) 2014 Elsevier Ltd. All rights reserved

Paleo-ecological analyses to assess long-term environmental effects of pearl farming in Western Australia

Small environmental disturbances accumulating over a long period of time may cause a regime shift in marine ecosystems, particularly in sensitive oligotrophic waters. Pearl oyster aquaculture, which has a 50 yr history in Australia, has been regarded as an anthropogenic activity with low environmental risk. To assess the long-term environmental effects of pearl oyster farming, sediment cores taken in Cygnet Bay, Western Australia, were used to reconstruct environmental processes covering an approximately 90 yr period. Biogeochemical parameters in sediment cores from inside and outside a pearl farming area displayed contrasting characteristics over time. Total organic carbon, total nitrogen, biogenic silica (BSi), and fine-grained sediment at the farming site displayed significant increases with the expansion of oyster stocking. In contrast, only small variations in response to climatic signals (rainfall and temperature) occurred over time in the cores outside the farm. The variation in the C:N ratio, delta C-13 and delta N-15 ranges over time suggested that increased organic matter was mainly contributed by autochthonous sources rather than terrestrial input. The sequential t-test for a regime shift detected approximately 2-to 3-fold increases in organic matter, 1-to 5-fold increases in silt proportion and 2-to 5-fold increases in BSi concentrations after pearl oyster farming, in contrast to the control site. The rapid development of modern long-line culture since the late 1980s is presumed to have been the dominant driver of environmental changes in sediments. The results provide insight into the magnitude of environmental change which can occur over decades as a result of even minimal anthropogenic activity

Identification and mRNA expression of two 17 beta-hydroxysteroid dehydrogenase genes in the marine mussel Mytilus galloprovincialis following exposure to endocrine disrupting chemicals

17 beta-Hydroxysteroid dehydrogenases (17 beta-HSDs) are multifunctional enzymes involved in the metabolism of steroids, fatty acids, retinoids and bile acid. In this study, two novel types of 17 beta-HSDs (named as MgHsd17b10 and MgHsd17b12) were cloned from Mytilus galloprovincialis by using rapid amplification of cDNA ends (RACE) approaches. Sequence analysis showed that MgHsd17b10 and MgHsd17b12 encoded a polypeptide of 259 and 325 amino acids, respectively. Phylogenetic analysis revealed that MgHsd17b10 and MgHsd17b12 were evolutionarily clustered with other invertebrate 17 beta-HSD type 10 and 17 beta-HSD type 12 homologues. The MgHsd17b10 and MgHsd17b12 transcripts could be detected in all examined tissues with higher expression levels in digestive glands and gonad. After exposed to endocrine disrupting chemicals (Bisphenol A or 2,2',4,4'-tetrabromodiphenyl ether), the expression of MgHsd17b10 and MgHsd17b12 transcripts was both down-regulated in digestive glands. These findings suggest that MgHsd17b10 and MgHsd17b12 perhaps play an important role in the endocrine regulation of M. galloprovincialis. (C) 2014 Elsevier B.V. All rights reserved.17 beta-Hydroxysteroid dehydrogenases (17 beta-HSDs) are multifunctional enzymes involved in the metabolism of steroids, fatty acids, retinoids and bile acid. In this study, two novel types of 17 beta-HSDs (named as MgHsd17b10 and MgHsd17b12) were cloned from Mytilus galloprovincialis by using rapid amplification of cDNA ends (RACE) approaches. Sequence analysis showed that MgHsd17b10 and MgHsd17b12 encoded a polypeptide of 259 and 325 amino acids, respectively. Phylogenetic analysis revealed that MgHsd17b10 and MgHsd17b12 were evolutionarily clustered with other invertebrate 17 beta-HSD type 10 and 17 beta-HSD type 12 homologues. The MgHsd17b10 and MgHsd17b12 transcripts could be detected in all examined tissues with higher expression levels in digestive glands and gonad. After exposed to endocrine disrupting chemicals (Bisphenol A or 2,2',4,4'-tetrabromodiphenyl ether), the expression of MgHsd17b10 and MgHsd17b12 transcripts was both down-regulated in digestive glands. These findings suggest that MgHsd17b10 and MgHsd17b12 perhaps play an important role in the endocrine regulation of M. galloprovincialis. (C) 2014 Elsevier B.V. All rights reserved