Volume 510 Number 7506

Editorials

Biosafety in the balance p.443

An accident with anthrax demonstrates that pathogen research always carries a risk of release — and highlights the need for rigorous scrutiny of gain-of-function flu studies.

doi: 10.1038/510443a

Storm warning p.444

Environmentalists are divided over whether it is possible to have a ‘good’ Anthropocene.

doi: 10.1038/510444b

Metrics market p.444

Measures of research impact are improving, but universities should be wary of their limits.

doi: 10.1038/510444a

News

News Features

Close collaborators p.458

Romance often sparks between colleagues, and scientists are no different. Nature profiles four super-couples who have combined love and the lab.

doi: 10.1038/510458a

Vitamins on trial p.462

After decades of study, researchers still can't agree on whether nutritional supplements actually improve health.

doi: 10.1038/510462a

News & Views

Identifying a hidden warhead p.476

A means of verifying that nuclear warheads to be dismantled are genuine items has been proposed that potentially reveals no information to an inspector about the design of the weapons. Two experts explain the ins and outs of the method and its implications for arms-control policy. See Article p.497

doi: 10.1038/510476a

To the rescue of old drugs p.477

A naturally occurring fungal compound has been found to restore the susceptibility of bacteria to a class of antibiotic that is currently considered to be our last defence against serious infections. See Article p.503

doi: 10.1038/510477a

A cool way to measure big G p.478

Published results of the gravitational constant, a measure of the strength of gravity, have failed to converge. An approach that uses cold atoms provides a new data point in the quest to determine this fundamental constant. See Letter p.518

doi: 10.1038/nature13507

Wobble puts RNA on target p.480

Enzymes that attach amino acids to transfer RNAs during protein synthesis must recognize both substrates specifically. Crystal structures reveal a mechanism that explains the RNA specificity for one such system. See Article p.507

doi: 10.1038/nature13502

Trawling for complements p.481

A method has been invented for determining nanoscale variations in the distribution of electric charge on surfaces. It has so far been used to examine specific inorganic materials, but could find widespread applications in imaging.

doi: 10.1038/510481a

Enzyme assembly line pictured p.482

Many enzymes form 'assembly lines' containing a series of catalytic modules. Visualization of how the structure of a module shifts during catalysis provides a clearer idea of how such enzymes work. See Article p.512 & Letter p.560

doi: 10.1038/nature13505

Review

An overview of N-heterocyclic carbenes p.485

N-heterocyclic carbenes are powerful tools in organic chemistry, with many commercially important applications; this overview describes their properties and potential uses.

doi: 10.1038/nature13384

Articles

A zero-knowledge protocol for nuclear warhead verification p.497

Future rounds of nuclear arms control would ideally involve direct inspection of nuclear warheads using procedures that give inspectors high confidence about the authenticity of submitted nuclear items yet give no information about their design; this is now shown to be achievable using zero-knowledge protocols in neutron imaging of nuclear warheads.

doi: 10.1038/nature13457

Aspergillomarasmine A overcomes metallo-β-lactamase antibiotic resistance p.503

The emergence of Gram-negative pathogens resistant to carbapenem antibiotics is a global health concern and carbapenem resistance often arises through acquisition of β-lactamase enzymes; this study identifies the natural fungal product aspergillomarasmine A as a metallo-β-lactamase inhibitor and a potential treatment to tackle carbapenem resistance.

doi: 10.1038/nature13445

Structure of a modular polyketide synthase p.512

Polyketide synthases are multidomain enzymes that produce polyketides, which form the basis of many therapeutic agents; here, electron cryo-microscopy is used to establish the structure of a bacterial full-length module, and to elucidate the structural basis of both intramodule and intermodule substrate transfer.

doi: 10.1038/nature13423

Letters

Precision measurement of the Newtonian gravitational constant using cold atoms p.518

Determination of the gravitational constant G using laser-cooled atoms and quantum interferometry, a technique that gives new insight into the systematic errors that have proved elusive in previous experiments, yields a value that has a relative uncertainty of 150 parts per million and which differs from the current recommended value by 1.5 combined standard deviations.

doi: 10.1038/nature13433

South Greenland ice-sheet collapse during Marine Isotope Stage 11 p.525

The isotopic composition of glacial sediment discharged into the ocean from south Greenland is used to identify a major reduction in the amount of that sediment derived from erosion of Greenland’s Precambrian bedrock, probably indicating the cessation of subglacial erosion and sediment transport during Marine Isotope Stage 11 as a result of the almost complete deglaciation of south Greenland.

doi: 10.1038/nature13456

Purkinje-cell plasticity and cerebellar motor learning are graded by complex-spike duration p.529

Recordings from monkeys during motor learning suggest that durations of complex-spike (CS) responses to climbing-fibre inputs are meaningful signals correlated across the Purkinje-cell population during motor learning; longer climbing-fibre bursts lead to longer-duration CS responses, larger synaptic depression and stronger learning, thus forming a graded instruction.

doi: 10.1038/nature13282

Decoding the regulatory landscape of medulloblastoma using DNA methylation sequencing p.537

Medulloblastoma is a malignant childhood brain tumour presenting major clinical challenges; here, a comprehensive genome-wide DNA methylation data set from human and mouse tumours, coupled with analysis of histone modifications, RNA transcripts and genome sequencing, uncovers a wealth of alterations that provide insights into the epigenetic regulation of transcription and genome organization in medulloblastoma pathogenesis.

doi: 10.1038/nature13268

Structural rearrangements of a polyketide synthase module during its catalytic cycle p.560

The polyketide synthase (PKS) mega-enzyme assembly line uses a modular architecture to synthesize diverse and bioactive natural products that often constitute the core structures or complete chemical entities for many clinically approved therapeutic agents. The architecture of a full-length PKS module from the pikromycin pathway of Streptomyces venezuelae creates a reaction chamber for the intramodule acyl carrier protein (ACP) domain that carries building blocks and intermediates between acyltransferase, ketosynthase and ketoreductase active sites (see accompanying paper). Here we determine electron cryo-microscopy structures of a full-length pikromycin PKS module in three key biochemical states of its catalytic cycle. Each biochemical state was confirmed by bottom-up liquid chromatography/Fourier transform ion cyclotron resonance mass spectrometry. The ACP domain is differentially and precisely positioned after polyketide chain substrate loading on the active site of the ketosynthase, after extension to the β-keto intermediate, and after β-hydroxy product generation. The structures reveal the ACP dynamics for sequential interactions with catalytic domains within the reaction chamber, and for transferring the elongated and processed polyketide substrate to the next module in the PKS pathway. During the enzymatic cycle the ketoreductase domain undergoes dramatic conformational rearrangements that enable optimal positioning for reductive processing of the ACP-bound polyketide chain elongation intermediate. These findings have crucial implications for the design of functional PKS modules, and for the engineering of pathways to generate pharmacologically relevant molecules.

doi: 10.1038/nature13409