Lipolytic enzymes and hydrolytic rancidity

Lipolysis, the enzymic hydrolysis of milk lipids to free fatty acids and partial glycerides, is a constant concern to the dairy industry because of the detrimental effcts it can have on the flvor and other properties of milk and milk products. However, free fatty acids also contribute to the desirable flavor of milk and milk products when present at low concentrations and, in some cheeses, when present at high concentrations. The enzymes responsible for the detrimental effects of lipolysis are of two main types: those indigenous to milk, and those of microbial origin. The major indigenous milk enzyme is lipoprotein lipase. It is active on the fat in natural milk fat globules only after their disruption by physical treatments or if certain blood serum lipoproteins are present. The major microbial lipases are produced by psychrotrophic bacteria. Many of these enzymes are heat stable and are particularly significant in stored products. Human milk differs from cows' milk in that it contains two lipases, a lipoprotein lipase and a bile salt-stimulated lipase. The ability of the latter to cause considerable hydrolysis of ingested milk lipids has important nutritional implications

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. 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; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation; analyses timings and patterns of tumour evolution; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity; and evaluates a range of more-specialized features of cancer genomes