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Volume 488 Issue 7411

Editorials

Safety shambles p.253

Lax management of Fukushima clean-up intensifies concerns over Japan's nuclear future.

doi: 10.1038/488253b

Repeat after me p.253

With plagiarism seemingly endemic in Romania, as well as rife among Europe's political class, a bid by academics to root out misconduct deserves widespread support.

doi: 10.1038/488253a

News

News Features

News & Views

CancerExploiting collateral damage p.284

Some mutations in tumour cells play no part in causing cancer, but they generate cellular weak spots that may allow tumour cells to be selectively killed by drugs. See Article p.337

doi: 10.1038/488284a

Applied physicsMasers made easy p.285

The technological potential of masers — the microwave equivalents of lasers — has been thwarted by their impractical operating conditions. A solid-state maser that works at room temperature may change that. See Letter p.353

doi: 10.1038/488285a

Cell biologyNeither brown nor white p.286

Fat cells are usually thought of as being either energy-storing white fat cells or food-burning brown fat cells. The identification of a third type of fat cell in mice and humans might open up new avenues for combating obesity.

doi: 10.1038/488286a

AstrophysicsOne of the first of the second stars p.288

The chemical content of a star that was born relatively shortly after the formation of the Milky Way calls into question conventional understanding of how stars formed in the early Universe.

doi: 10.1038/488288a

NeuroscienceCircuits drive cell diversity p.289

Neurons of the same type can show functional differences. It turns out that this diversity is in part the result of the cells' adaptation to their specific neural networks. See Letter p.375

doi: 10.1038/488289a

OceanographyThe trouble with the bubble p.290

Past studies have suggested that the ocean's nitrogen budget has a deficit of fixed nitrogen. This view may now change, thanks to upward revisions of the rate of nitrogen input through biological activity. See Letter p.361

doi: 10.1038/nature11481

Articles

Passenger deletions generate therapeutic vulnerabilities in cancer p.337

Inactivation of tumour-suppressor genes by homozygous deletion is a prototypic event in the cancer genome, yet such deletions often encompass neighbouring genes. We propose that homozygous deletions in such passenger genes can expose cancer-specific therapeutic vulnerabilities when the collaterally deleted gene is a member of a functionally redundant family of genes carrying out an essential function. The glycolytic gene enolase 1 (ENO1) in the 1p36 locus is deleted in glioblastoma (GBM), which is tolerated by the expression of ENO2. Here we show that short-hairpin-RNA-mediated silencing of ENO2 selectively inhibits growth, survival and the tumorigenic potential of ENO1-deleted GBM cells, and that the enolase inhibitor phosphonoacetohydroxamate is selectively toxic to ENO1-deleted GBM cells relative to ENO1-intact GBM cells or normal astrocytes. The principle of collateral vulnerability should be applicable to other passenger-deleted genes encoding functionally redundant essential activities and provide an effective treatment strategy for cancers containing such genomic events.

doi: 10.1038/nature11331

Division and subtraction by distinct cortical inhibitory networks in vivo p.343

Brain circuits process information through specialized neuronal subclasses interacting within a network. Revealing their interplay requires activating specific cells while monitoring others in a functioning circuit. Here we use a new platform for two-way light-based circuit interrogation in visual cortex in vivo to show the computational implications of modulating different subclasses of inhibitory neurons during sensory processing. We find that soma-targeting, parvalbumin-expressing (PV) neurons principally divide responses but preserve stimulus selectivity, whereas dendrite-targeting, somatostatin-expressing (SOM) neurons principally subtract from excitatory responses and sharpen selectivity. Visualized in vivo cell-attached recordings show that division by PV neurons alters response gain, whereas subtraction by SOM neurons shifts response levels. Finally, stimulating identified neurons while scanning many target cells reveals that single PV and SOM neurons functionally impact only specific subsets of neurons in their projection fields. These findings provide direct evidence that inhibitory neuronal subclasses have distinct and complementary roles in cortical computations.

doi: 10.1038/nature11347

Letters