A new model of glucocorticoid-induced metanephric maldevelopment

Summary A new experimental model of glucocortocoid-induced tubular cyst formation has been developed in metanephric organ culture. The addition of cortisol (1.4×10^–5 M) to chemically defined serum-free culture medium produces cystic changes during in vitro nephrogenesis. The model isolates the role of glucocorticoids in experimental cyst formation.Acknowledgment. This work has been supported by Basil O'Connor Starter Research Grant No.5-349 from the March of Dimes Birth Defects Foundation.     

Dark matter maps reveal cosmic scaffolding

Ordinary baryonic particles (such as protons and neutrons) account for only one-sixth of the total matter in the Universe. The remainder is a mysterious 'dark matter' component, which does not interact via electromagnetism and thus neither emits nor reflects light. As dark matter cannot be seen directly using traditional observations, very little is currently known about its properties. It does interact via gravity, and is most effectively probed through gravitational lensing: the deflection of light from distant galaxies by the gravitational attraction of foreground mass concentrations. This is a purely geometrical effect that is free of astrophysical assumptions and sensitive to all matter--whether baryonic or dark. Here we show high-fidelity maps of the large-scale distribution of dark matter, resolved in both angle and depth. We find a loose network of filaments, growing over time, which intersect in massive structures at the locations of clusters of galaxies. Our results are consistent with predictions of gravitationally induced structure formation, in which the initial, smooth distribution of dark matter collapses into filaments then into clusters, forming a gravitational scaffold into which gas can accumulate, and stars can be built.     

Whole-genome analysis informs breast cancer response to aromatase inhibition

To correlate the variable clinical features of oestrogen-receptor-positive breast cancer with somatic alterations, we studied pretreatment tumour biopsies accrued from patients in two studies of neoadjuvant aromatase inhibitor therapy by massively parallel sequencing and analysis. Eighteen significantly mutated genes were identified, including five genes (RUNX1, CBFB, MYH9, MLL3 and SF3B1) previously linked to haematopoietic disorders. Mutant MAP3K1 was associated with luminal A status, low-grade histology and low proliferation rates, whereas mutant TP53 was associated with the opposite pattern. Moreover, mutant GATA3 correlated with suppression of proliferation upon aromatase inhibitor treatment. Pathway analysis demonstrated that mutations in MAP2K4, a MAP3K1 substrate, produced similar perturbations as MAP3K1 loss. Distinct phenotypes in oestrogen-receptor-positive breast cancer are associated with specific patterns of somatic mutations that map into cellular pathways linked to tumour biology, but most recurrent mutations are relatively infrequent. Prospective clinical trials based on these findings will require comprehensive genome sequencing.     

Early star-forming galaxies and the reionization of the Universe

Star-forming galaxies trace cosmic history. Recent observational progress with the NASA Hubble Space Telescope has led to the discovery and study of the earliest known galaxies, which correspond to a period when the Universe was only ～800 million years old. Intense ultraviolet radiation from these early galaxies probably induced a major event in cosmic history: the reionization of intergalactic hydrogen.     

Common variants at 11p13 are associated with susceptibility to tuberculosis

After imputation of data from the 1000 Genomes Project into a genome-wide dataset of Ghanaian individuals with tuberculosis and controls, we identified a resistance locus on chromosome 11p13 downstream of the WT1 gene (encoding Wilms tumor 1). The strongest signal was obtained at the rs2057178 SNP (P = 2.63 × 10(-9)). Replication in Gambian, Indonesian and Russian tuberculosis case-control study cohorts increased the significance level for the association with this SNP to P = 2.57 × 10(-11).     

The defensive function of cyanogenesis in natural populations

Summary Detailed ecological studies of some maritime populations of Lotus corniculatus L. have shown that the distribution of the cyanogenic form of this plant is directly related to the distribution and density of molluscs which graze selectively the acyanogenic form. This work, on a genetic polymorphism, is interpreted as giving direct evidence of chemical defence in natural populations.Acknowledgment. We are most grateful to the Science Research Council (B/RG/3539, W.M.E. and D.A.J.) and to the Natural Environment Research Council and the Sir Philip Reckitt Educational Trust (research studentship, R.J.K.) for the financial support of this work.