Modulation of host cell processes by T3SS effectors

Two of the enteric Escherichia coli pathotypes-enteropathogenic E. coli (EPEC) and enterohaemorrhagic E. coli (EHEC)-have a conserved type 3 secretion system which is essential for virulence. The T3SS is used to translocate between 25 and 50 bacterial proteins directly into the host cytosol where they manipulate a variety of host cell processes to establish a successful infection. In this chapter, we discuss effectors from EPEC/EHEC in the context of the host proteins and processes that they target-the actin cytoskeleton, small guanosine triphosphatases and innate immune signalling pathways that regulate inflammation and cell death. Many of these translocated proteins have been extensively characterised, which has helped obtain insights into the mechanisms of pathogenesis of these bacteria and also understand the host pathways they target in more detail. With increasing knowledge of the positive and negative regulation of host signalling pathways by different effectors, a future challenge is to investigate how the specific effector repertoire of each strain cooperates over the course of an infection

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

Field trial of a genetically improved baculovirus insecticide

IMPROVEMENT of biological pesticides through genetic modification has enormous potential and the insect baculoviruses are particularly amenable to this approach1,2. A key aim of genetic engineering is to increase their speed of kill, primarily by the incorporation of genes which encode arthropod or bacterially derived insect-selective toxins3–11, insect hormones12,13 or enzymes14,15. We report here the first, to our knowledge, field trial of a genetically improved nuclear polyhedrosis virus of the alfalfa looper, Autogmpha californica (AcNPV) that expresses an insectselective toxin gene (AaHIT) derived from the venom of the scorpion Androclonus australisl6–18. Previous laboratory assays with the cabbage looper, Trichoplusia ni, demonstrated a 25% reduction in time to death compared to the wild-type virus, but unaltered pathogenicity6 and host range19. In the field, the modified baculovirus killed faster, resulting in reduced crop damage and it appeared to reduce the secondary cycle of infection compared to the wild-type virus

Water intake and digestive metabolism of broilers fed all-vegetable diets containing acidulated soybean soapstock

A study was conducted to compare live performance and digestive metabolism of broiler chickens fed all-vegetable diets (All-Veg) compared to a regular diet including animal by-products. Three feeds were formulated and provided to broilers according to the feeding program: pre-starter from 1 to 10 days, starter from 11 to 21 days, and grower from 21 to 35 days. All feeds had corn and soybean meal as major ingredients; however, two of them were all-vegetable diets having either Degummed Soybean Oil (DSO) or Acidulated Soybean Soapstock (ASS) as fat sources. The third diet included poultry by-product and poultry fat. A total number of 360 day-old broiler chicks were allocated to 1m² battery cages, 10 chicks in each, and 12 replicates per treatment. Live performance was similar between groups of birds receiving the different diets with the exception of weight gain, which was increased for birds fed the All-Veg diet with ASS. Birds fed All-Veg diets had increased water intake and produced more excreta with a concurrent reduced feed metabolizability at both ages, regardless of fat source. Metabolizable Energy was not different for the three diets