Volume 521 Number 7553

Editorials

Trading places p.393

Scientists have a valuable part to play in clarifying the impacts of a proposed trade treaty between the United States and Europe.

doi: 10.1038/521393a

Wakey wakey p.394

Sleeping-beauty papers offer hope that authors of uncited works are in good company.

doi: 10.1038/521394a

Silicon smarts p.394

A package of articles in Nature assesses the state of artificial-intelligence research.

doi: 10.1038/521394b

News

News Features

Laser weapons get real p.408

Long a staple of science fiction, laser weapons are edging closer to the battlefield — thanks to optical fibres.

doi: 10.1038/521408a

Clever fish p.412

By revealing that fish cooperate, cheat and punish, Redouan Bshary has challenged ideas about brain evolution.

doi: 10.1038/521412a

News & Views

Robots with instincts p.426

An evolutionary algorithm has been developed that allows robots to adapt to unforeseen change. The robots learn behaviours quickly and instinctively by mining the memory of their past achievements. See Letter p.503

doi: 10.1038/521426a

Polarized transport in the Golgi apparatus p.427

Proteins can be transported in either direction across a cellular organelle called the Golgi apparatus. It emerges that CDC42, a molecule that confers cell polarity, acts to control the directionality of transport in the Golgi. See Letter p.529

doi: 10.1038/nature14521

The origins of a climate oscillation p.428

An index of water-circulation strength in the North Atlantic Ocean has been derived from sea-level measurements. This provides fresh evidence of the ocean's leading role in multidecadal climate variability. See Letter p.508

doi: 10.1038/521428a

A waste of insulin interference p.430

Many people with cancer die from a wasting disorder called cancer-associated cachexia. Two studies in fruit flies show that inhibition of insulin signalling causes cachexia-like organ wasting.

doi: 10.1038/521430a

Taking the bad with the good p.431

Modelling of the interactions between antibiotic production and antibiotic degradation reveals that these opposing activities are key to maintaining diversity in microbial communities. See Letter p.516

doi: 10.1038/nature14525

The middle Pliocene gets crowded p.432

New hominin fossils discovered in Ethiopia, dated to between 3.5 million and 3.3 million years ago, suggest that species diversity may have been as high during early human evolution as in later periods. See Article p.483

doi: 10.1038/521432a

Articles

New species from Ethiopia further expands Middle Pliocene hominin diversity p.483

A new hominin species, Australopithecus deyiremeda, which lived between 3.5 and 3.3 million years ago, at around the same time as species such as Au. afarensis (‘Lucy’), is discovered in Ethiopia; its morphology suggests that some dental features traditionally associated with later genera such as Paranthropus and Homo emerged earlier than previously thought.

doi: 10.1038/nature14448

Whole–genome characterization of chemoresistant ovarian cancer p.489

Whole-genome sequencing of tumour and germline DNA samples from 92 patients with high-grade serous ovarian cancer identifies frequent gene breakages that inactivate the tumour suppressors RB1, NF1, RAD51B and PTEN, and contribute to chemotherapy resistance; acquired resistance was associated with diverse mechanisms such as reversions of germline BRCA1/2 mutations and overexpression of the drug efflux pump MDR1.

doi: 10.1038/nature14410

Letters

Extreme ultraviolet high-harmonic spectroscopy of solids p.498

Intense light interacting with a thin film of silicon dioxide is used to generate broadband extreme ultraviolet radiation; the spectra reveal detailed information on the energy dispersion of the conduction band of silicon dioxide, which is at present inaccessible by conventional photoemission spectroscopy.

doi: 10.1038/nature14456

Robots that can adapt like animals p.503

An intelligent trial-and-error learning algorithm is presented that allows robots to adapt in minutes to compensate for a wide variety of types of damage.

doi: 10.1038/nature14422

Ocean impact on decadal Atlantic climate variability revealed by sea-level observations p.508

The circulation of the North Atlantic Ocean, interpreted via the sea level gradient along the US coast, is found to respond to atmospheric drivers from the North Atlantic Oscillation, and in turn influences the oceanic temperature changes characterized by Atlantic Multidecadal Oscillation; in this way, ocean circulation acts as the intermediary between atmospheric and ocean oscillations.

doi: 10.1038/nature14491

Diverse coupling of neurons to populations in sensory cortex p.511

Exploring the relationship between population coupling and neuronal activity reveals that neighbouring neurons can differ in their coupling to the overall firing rate of the population, the circuitry of which may potentially help to explain the complex activity patterns in cortical populations.

doi: 10.1038/nature14273

Coordinated regulation of bidirectional COPI transport at the Golgi by CDC42 p.529

The COPI complex, which has a role in retrograde transport through the Golgi, is shown to also mediate anterograde tubular transport through the Golgi; in response to external stimuli, the small GTPase CDC42 acts as an essential modulator of bidirectional Golgi transport, and promotes the sorting of cargoes destined for anterograde transport into the tubules at the expense of those targeted for retrograde transport.

doi: 10.1038/nature14457

MAD2L2 controls DNA repair at telomeres and DNA breaks by inhibiting 5′ end resection p.537

Appropriate repair of DNA lesions and the inhibition of DNA repair activities at telomeres are crucial to prevent genomic instability. By fuelling the generation of genetic alterations and by compromising cell viability, genomic instability is a driving force in cancer and ageing. Here we identify MAD2L2 (also known as MAD2B or REV7) through functional genetic screening as a novel factor controlling DNA repair activities at mammalian telomeres. We show that MAD2L2 accumulates at uncapped telomeres and promotes non-homologous end-joining (NHEJ)-mediated fusion of deprotected chromosome ends and genomic instability. MAD2L2 depletion causes elongated 3′ telomeric overhangs, indicating that MAD2L2 inhibits 5′ end resection. End resection blocks NHEJ while committing to homology-directed repair, and is under the control of 53BP1, RIF1 and PTIP. Consistent with MAD2L2 promoting NHEJ-mediated telomere fusion by inhibiting 5′ end resection, knockdown of the nucleases CTIP or EXO1 partially restores telomere-driven genomic instability in MAD2L2-depleted cells. Control of DNA repair by MAD2L2 is not limited to telomeres. MAD2L2 also accumulates and inhibits end resection at irradiation-induced DNA double-strand breaks and promotes end-joining of DNA double-strand breaks in several settings, including during immunoglobulin class switch recombination. These activities of MAD2L2 depend on ATM kinase activity, RNF8, RNF168, 53BP1 and RIF1, but not on PTIP, REV1 and REV3, the latter two acting with MAD2L2 in translesion synthesis. Together, our data establish MAD2L2 as a crucial contributor to the control of DNA repair activity by 53BP1 that promotes NHEJ by inhibiting 5′ end resection downstream of RIF1.

doi: 10.1038/nature14216