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

Leptospira interrogans activation of peripheral blood monocyte glycolipoprotein demonstrated in whole blood by the release of IL-6

Glycolipoprotein (GLP) from pathogenic serovars of Leptospira has been implicated in the pathogenesis of leptospirosis by its presence in tissues of experimental animals with leptospirosis, the inhibition of the Na,K-ATPase pump activity, and induced production of cytokines. The aims of the present study were to investigate the induction of IL-6 by GLP in peripheral blood mononuclear cells (PBMC) and to demonstrate monocyte stimulation at the cellular level in whole blood from healthy volunteers. PBMC were stimulated with increasing concentrations (5 to 2500 ng/ml) of GLP extracted from the pathogenic L. interrogans serovar Copenhageni, lipopolysaccharide (positive control) or medium (negative control), and supernatants were collected after 6, 20/24, and 48 h, and kept at -80ºC until use. Whole blood was diluted 1:1 in RPMI medium and cultivated for 6 h, with medium, GLP and lipopolysaccharide as described above. Monensin was added after the first hour of culture. Supernatant cytokine levels from PBMC were measured by ELISA and intracellular IL-6 was detected in monocytes in whole blood cultures by flow-cytometry. Monocytes were identified in whole blood on the basis of forward versus side scatter parameters and positive reactions with CD45 and CD14 antibodies. GLP ( > or = 50 ng/ml)-induced IL-6 levels in supernatants were detected after 6-h incubation, reaching a peak after 20/24 h. The percentage of monocytes staining for IL-6 increased with increasing GLP concentration. Thus, our findings show a GLP-induced cellular activation by demonstrating the ability of GLP to induce IL-6 and the occurrence of monocyte activation in whole blood at the cellular level

Technological Trends in the Sport Field: Which Application Areas and Challenges?

This paper investigates the application of new technologies in the sport field. Technology, mainly information technology (IT) and internet, is deeply changing the overall picture of the sport sector. New technologies facilitate the knowledge transfer in the sporting event management process, such as the Olympic Games; at the same time, the innovative techniques can significantly affect the athletes’ performance and the social integration of disabled persons. There is an explosion of technology applications in the sport field in different sub-organizational areas, but this phenomenon is still underrepresented in the literature. This paper aims to identify and evidence the main application areas and challenges faced by technology in the sport setting. This study, through a review of the literature, represents a research starting point that allows us to systematize and clarify the main contributions on this topic and to identify new research perspective

Dynamic evolution of the alpha (a) and beta (ß) keratins has accompanied integument diversification and the adaptation of birds into novel lifestyles

Background: Vertebrate skin appendages are constructed of keratins produced by multigene families. Alpha (a) keratins are found in all vertebrates, while beta (ß) keratins are found exclusively in reptiles and birds. We have studied the molecular evolution of these gene families in the genomes of 48 phylogenetically diverse birds and their expression in the scales and feathers of the chicken.Results: We found that the total number of a-keratins is lower in birds than mammals and non-avian reptiles, yet two a-keratin genes (KRT42 and KRT75) have expanded in birds. The ß-keratins, however, demonstrate a dynamic evolution associated with avian lifestyle. The avian specific feather ß-keratins comprise a large majority of the total number of ß-keratins, but independently derived lineages of aquatic and predatory birds have smaller proportions of feather ß-keratin genes and larger proportions of keratinocyte ß-keratin genes. Additionally, birds of prey have a larger proportion of claw ß-keratins. Analysis of a- and ß-keratin expression during development of chicken scales and feathers demonstrates that while a-keratins are expressed in these tissues, the number and magnitude of expressed ß-keratin genes far exceeds that of a-keratins.Conclusions: These results support the view that the number of a- and ß-keratin genes expressed, the proportion of the ß-keratin subfamily genes expressed and the diversification of the ß-keratin genes have been important for the evolution of the feather and the adaptation of birds into multiple ecological niches

First measurement of Xi(0)(c) production in pp collisions at root s=7 TeV

The production of the charm-strange baryon Xi(0)(c) is measured for the first time at the LHC via its semileptonic decay into e(+) Xi(-) nu(e) in ppcollisions at root s = 7 TeV with the ALICE detector. The transverse momentum ( p(T)) differential cross section multiplied by the branching ratio is presented in the interval 1 < p(T)< 8 GeV/c at mid-rapidity, vertical bar y vertical bar < 0.5. The transverse momentum dependence of the Xi(0)(c) baryon production relative to the D-0 meson production is compared to predictions of event generators with various tunes of the hadronisation mechanism, which are found to underestimate the measured cross-section ratio. (C) 2018 The Author(s). Published by Elsevier B.V