The evolution and appearance of c3 duplications in fish originate an exclusive teleost c3 gene form with anti- inflammatory activity

12 páginas, 6 figuras, 3 tablas.-- This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedThe complement system acts as a first line of defense and promotes organism homeostasis by modulating the fates of diverse physiological processes. Multiple copies of component genes have been previously identified in fish, suggesting a key role for this system in aquatic organisms. Herein, we confirm the presence of three different previously reported complement c3 genes (c3.1, c3.2, c3.3) and identify five additional c3 genes (c3.4, c3.5, c3.6, c3.7, c3.8) in the zebrafish genome. Additionally, we evaluate the mRNA expression levels of the different c3 genes during ontogeny and in different tissues under steady-state and inflammatory conditions. Furthermore, while reconciling the phylogenetic tree with the fish species tree, we uncovered an event of c3 duplication common to all teleost fishes that gave rise to an exclusive c3 paralog (c3.7 and c3.8). These paralogs showed a distinct ability to regulate neutrophil migration in response to injury compared with the other c3 genes and may play a role in maintaining the balance between inflammatory and homeostatic processes in zebrafishThis work has been funded by the project CSD2007-00002 “Aquagenomics” from the Spanish Ministerio de Ciencia e Innovación, the ITN 289209 “FISHFORPHARMA” (EU) and project 201230E057 from the Agencia Estatal Consejo Superior de Investigaciones Científicas (CSIC).Peer reviewe

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

Dual Energy CT (DECT) monochromatic imaging: added value of Adaptive Statistical Iterative Reconstructions (ASIR) in portal venography

OBJECTIVE: To investigate the effect of the adaptive statistical iterative reconstructions (ASIR) on image quality in portal venography by dual energy CT (DECT) imaging. MATERIALS AND METHODS: DECT scans of 45 cirrhotic patients obtained in the portal venous phase were analyzed. Monochromatic images at 70keV were reconstructed with the following 4 ASIR percentages: 0%, 30%, 50%, and 70%. The image noise (IN) (standard deviation, SD) of portal vein (PV), the contrast-to-noise-ratio (CNR), and the subjective score for the sharpness of PV boundaries, and the diagnostic acceptability (DA) were obtained. The IN, CNR, and the subjective scores were compared among the four ASIR groups. RESULTS: The IN (in HU) of PV (10.05±3.14, 9.23±3.05, 8.44±2.95 and 7.83±2.90) decreased and CNR values of PV (8.04±3.32, 8.95±3.63, 9.80±4.12 and 10.74±4.73) increased with the increase in ASIR percentage (0%, 30%, 50%, and 70%, respectively), and were statistically different for the 4 ASIR groups (p<0.05). The subjective scores showed that the sharpness of portal vein boundaries (3.13±0.59, 2.82±0.44, 2.73±0.54 and 2.07±0.54) decreased with higher ASIR percentages (p<0.05). The subjective diagnostic acceptability was highest at 30% ASIR (p<0.05). CONCLUSIONS: 30% ASIR addition in DECT portal venography could improve the 70 keV monochromatic image quality

Reducing the Radiation Dose for Computed Tomography Colonography Using Model-Based Iterative Reconstruction.

Purpose To determine whether radiation doses during computed tomography (CT) colonography (CTC) can be further reduced while maintaining image quality using model-based iterative reconstruction (MBIR