Novel mutations target distinct subgroups of medulloblastoma

Medulloblastoma is a malignant childhood brain tumour comprising four discrete subgroups. Here, to identify mutations that drive medulloblastoma, we sequenced the entire genomes of 37 tumours and matched normal blood. One-hundred and thirty-six genes harbouring somatic mutations in this discovery set were sequenced in an additional 56 medulloblastomas. Recurrent mutations were detected in 41 genes not yet implicated in medulloblastoma; several target distinct components of the epigenetic machinery in different disease subgroups, such as regulators of H3K27 and H3K4 trimethylation in subgroups 3 and 4 (for example, KDM6A and ZMYM3), and CTNNB1-associated chromatin re-modellers in WNT-subgroup tumours (for example, SMARCA4 and CREBBP). Modelling of mutations in mouse lower rhombic lip progenitors that generate WNT-subgroup tumours identified genes that maintain this cell lineage (DDX3X), as well as mutated genes that initiate (CDH1) or cooperate (PIK3CA) in tumorigenesis. These data provide important new insights into the pathogenesis of medulloblastoma subgroups and highlight targets for therapeutic development.     

Key issues in the quality assurance of the One Number Census

As part of the 2001 Census, the One Number Census project estimated and adjusted the Census database for underenumeration. As a result of the highly innovative One Number Census and the Quality Assurance process it encompassed, it was also ensured that robust results could be obtained for each local authority area. This article examines some of the issues and analyses that were undertaken as part of that assessment of the 2001 Census population counts for England and Wales. The article firstly highlights the key issues surrounding the implementation of the 2001 Census fieldwork. The article then explores the 2001 Census results through a series of demographic analyses to illustrate the sorts of issues investigated during the One Number Census Quality Assurance process itself. These analyses look at the patterns contained within the results, and comparisons with key alternative sources of population counts. Overall, these in-depth analyses and investigations provide further credence to the plausibility of the One Number Census results.     

Evolution,consequences and future of plant and animal domestication

Domestication interests us as the most momentous change in Holocene human history. Why did it operate on so few wild species, in so few geographic areas? Why did people adopt it at all, why did they adopt it when they did, and how did it spread? The answers to these questions determined the remaking of the modern world, as farmers spread at the expense of hunter-gatherers and of other farmers.     

The matches,achieved by natural selection,between biological capacities and their natural loads

Natural selection tends to eliminate unutilized capacities because of their costs. Hence we ask how large are the reserve capacities by which biological capacities exceed natural loads, and how closely are related biological capacities matched to each other. Measured capacities (V_max values) of small intestinal brush-border nutrient transporters are typically around twice their natural loads (dietary intakes of their substrates); the ratio is higher for a transporter of a hyperessential nutrient. Preliminary evidence suggests matching of capacities between different steps in carbohydrate metabolism, and between the intestine, liver, kidneys, and spleen. Symmorphosis — the postulated matching of capacities to each other and to loads — is a testable hypothesis of economic design, useful in detecting and explaining cases of apparently uneconomic design.