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

Consensus guidelines for the use and interpretation of angiogenesis assays

The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference

Condition-dependent sex allocation by clones of a galling aphid

Local mate competition (LMC) has been postulated to be the primary factor of female-biased sex allocation. In animals such as aphids that exhibit seasonal alternations of clonal and sexual reproduction, there is a high possibility of intra-clonal mating and LMC. This possibility is more plausible for more fecund clones, but out-breeding is predicted for less fecund clones. We hypothesize that clones that are more fecund will gain higher fitness returns by reducing investment in males because of more intense LMC among clonal males. We tested this hypothesis by elucidating the clonal sex allocation patterns of the galling aphid Kaltenbachiella japonica, in which inbreeding and LMC appear to be common. Winged mothers that emerge from a gall, belonging to the same clone, produced males and sexual females asexually on a branch, without dispersing to other trees. The heavier the gall, the more winged mothers were produced from the gall. Individual mothers produced a constant number of males and a variable number of females. The clonal sex allocation to males was 39.8%, on average, and decreased with increasing gall weight. This result showed that clones that were more fecund exhibited more female-biased sex allocation and thus supported our hypothesis. Furthermore, our results corroborated Stubblefield and Seger's hypothesis for sex allocation in patch structure rather than Yamaguchi's constant male hypothesis. We conclude that K. japonica clones are able to adjust their sex allocation patterns adaptively depending on the quality of resources in the galls

Distinct responses of Gulf of Mexico phytoplankton communities to crude oil and the dispersant corexit® Ec9500A under different nutrient regimes

This study examines the potential effects of exposure to South Louisiana sweet crude oil (LSC), Corexit(A (R)) EC9500A, and dispersed oil on enclosed phytoplankton communities under different nutrient regimes. Three distinct microcosm experiments were conducted for 10 days to assess changes to the structure of natural communities from the Gulf of Mexico as quantified by temporal changes in the biomasses of different phytoplankton groups. Concentration of NO3, Si and PO4 were 0.83, 0.99 and 0.09 mu M for the unenriched treatments and 14.07, 13.01 and 0.94 mu M for the enriched treatments, respectively. Overall, the contaminants LSC and Corexit(A (R)) EC9500A led to a decrease in the number of sensitive species and an increase in more resistant species. Phytoplankton communities showed more sensitivity to LSC under nutrient-limited conditions. The addition of nutrients to initially nutrient-limited treatments lessened the inhibitory effect of LSC in the short term. Centric diatoms benefited most from this enrichment, but pennate diatoms demonstrated considerably greater tolerance to crude oil at low crude oil concentrations in nutrient-enriched treatments. Dinoflagellates showed relatively higher tolerance in nutrient-limited treatments and high crude oil concentrations. Corexit(A (R)) EC9500A inputs significantly increased the toxicity of crude oil. Corexit(A (R)) EC9500A alone had a highly inhibitory effect at 63 ppm on phytoplankton communities. This study highlights the fact that different nutrient regimes play a major role in determining the shifts of the phytoplankton community in response to exposure to different concentrations of crude oil and dispersant. Determination of the functional equivalence of shifted phytoplankton groups could complement our research and allow for more pertinent extrapolation to real world conditions

Could digital imaging be an alternative for digital colorimeters?

This study evaluated the colour parameters of composite and ceramic shade guides determined using a colorimeter and digital imaging method with illuminants at different colour temperatures. Two different resin composite shade guides, namely Charisma (Heraeus Kulzer) and Premise (Kerr Corporation), and two different ceramic shade guides, Vita Lumin Vacuum (VITA Zahnfabrik) and Noritake (Noritake Co.), were evaluated at three different colour temperatures (2,700 K, 2,700-6,500 K, and 6500 K) of illuminants. Ten shade tabs were selected (A1, A2, A3, A3,5, A4, B1, B2, B3, C2 and C3) from each shade guide. CIE Lab values were obtained using digital imaging and a colorimeter (ShadeEye NCC Dental Chroma Meter, Shofu Inc.). The data were analysed using two-way ANOVA, and Pearson's correlation. While mean L* values of both composite and ceramic shade guides were not affected from the colour temperature, L* values obtained with the colorimeter showed significantly lower values than those of the digital imaging (p 0.05). For both composite and ceramic shade guides, L* and b* values obtained from colorimeter and digital imaging method presented a high level of correlation. High-level correlations were also acquired for a* values in all shade guides except for the Charisma composite shade guide. Digital imaging method could be an alternative for the colorimeters unless the proper object-camera distance, digital camera settings and suitable illumination conditions could be supplied. However, variations in shade guides, especially for composites, may affect the correlation