Volume 526 Issue 7573


After Asilomar p.293

Scientist-led conferences are no longer the best way to resolve debates on controversial research.

doi: 10.1038/526293b

A shift in climate p.293

The Intergovernmental Panel on Climate Change has done much to alert politicians to the effects of global warming. But to push climate change up the agenda, it will need to do the same for the public.

doi: 10.1038/526293a

The worm returns p.294

The wiring diagram of the male nematode’s nervous system is only a beginning.

doi: 10.1038/526294a


News Features

News & Views

Decrypting a brain enigma p.326

The combined neuronal activity of two seemingly opposite types of Purkinje cell in the brain's cerebellum has been found to be required to control the jerky eye movements known as saccades in monkeys. See Letter p.439

doi: 10.1038/526326a

The long future of Antarctic melting p.327

Simulations show that melting of the Antarctic ice sheet in response to climate change could raise the global sea level by up to 3 metres by the year 2300 and continue for thousands of years thereafter. See Letter p.421

doi: 10.1038/526327a

A bacterial nudge to T-cell function p.328

The epithelial cells that line the intestine have been found to sense tight attachment of bacteria, and to respond by producing proteins that shape the effector functions of the immune system's TH17 cells.

doi: 10.1038/526328a

Sometimes γ-rays come in twos p.330

Breakthrough measurements of a rare decay process in an excited barium nucleus pave the way for the development of techniques that probe the structure and decay modes of atomic nuclei. See Letter p.406

doi: 10.1038/526330a

Deep brain stimulation for Rett syndrome p.331

Mutations in the gene MECP2 cause an intellectual-disability disorder called Rett syndrome. In a mouse model, electrical stimulation of deep brain regions is found to ameliorate some of the features of the syndrome. See Letter p.430

doi: 10.1038/526331a

Microscopic friction emulators p.332

Cold ions sliding across periodic energy-potential patterns formed by lasers have been used to elucidate the physics of dry friction between crystals. Experiments with no more than six ions suffice to explore a vast domain of frictional forces.

doi: 10.1038/526332a

Visible inequality breeds more inequality p.333

Experiments suggest that when people can see wealth inequality in their social network, this propels further inequality through reduced cooperation and reduced social connectivity. See Letter p.426

doi: 10.1038/526333a


Progress and challenges in probing the human brain p.371

This Review evaluates current techniques used to investigate human brain function, discusses the successes and limitations of these techniques to test hypotheses about causal mechanisms, and looks to future directions and implementation of these techniques in real-world problems.

doi: 10.1038/nature15692


Glia-derived neurons are required for sex-specific learning in C. elegans p.385

In the worm C. elegans, a previously unidentified pair of bilateral neurons in the male (termed MCMs) are shown to arise from differentiated glial cells upon sexual maturation; these neurons are essential for a male-specific form of associative learning which balances chemotactic responses with reproductive priorities.

doi: 10.1038/nature15700

Molecular basis of ligand recognition and transport by glucose transporters p.391

The SLC2 family glucose transporters facilitate the transport of glucose and other monosaccharides across biological membranes; the X-ray crystal structure of human GLUT3 has been solved in outward-open and outward-occluded conformations and a model for how the membrane protein rearranges itself during a complete transport cycle has been proposed.

doi: 10.1038/nature14655

Structure and mechanism of the mammalian fructose transporter GLUT5 p.397

This study has determined the X-ray crystal structures of GLUT5 from Rattus norvegicus in an open, outward-facing conformation and GLUT5 from Bos taurus in an open, inward-facing conformation; comparison of these structures with previously published structures of the related Escherichia coli d-xylose:H+ symporter XylE suggests that transport in GLUT5 is controlled by both a global ‘rocker-switch’-type motion and a local ‘gated-pore’-type transport mechanism.

doi: 10.1038/nature14909


A two-qubit logic gate in silicon p.410

A high-fidelity two-qubit CNOT logic gate is presented, which is realized by combining single- and two-qubit operations with controlled phase operations in a quantum dot system using the exchange interaction.

doi: 10.1038/nature15263

Peptoid nanosheets exhibit a new secondary-structure motif p.415

Some peptoids—synthetic structural relatives of polypeptides—can assemble into two-dimensional nanometre-scale sheets; simulations and experimental measurements show that these nanosheets contain a motif unique to peptoids, namely zigzag Σ-strands, which interlock and enable the nanosheets to extend in two dimensions only.

doi: 10.1038/nature15363

The multi-millennial Antarctic commitment to future sea-level rise p.421

Despite computational and methodological uncertainties, and a wide range of potential greenhouse gas emissions, here millennial-scale simulations of the Antarctic Ice Sheet in a warming climate show that most of Antarctica’s fringing ice shelves will collapse, leading to a rise in sea level of up to 3 metres by 2300.

doi: 10.1038/nature15706

Inequality and visibility of wealth in experimental social networks p.426

Wealth inequality and wealth visibility can potentially affect overall levels of cooperation and economic success, and an online experiment was used to test how these factors interact; wealth inequality by itself did not substantially damage overall cooperation or overall wealth, but making wealth levels visible had a detrimental effect on social welfare.

doi: 10.1038/nature15392

Forniceal deep brain stimulation rescues hippocampal memory in Rett syndrome mice p.430

Deep brain stimulation (DBS) of the fimbria–fornix—a region that provides input to the hippocampus—is shown to restore hippocampus-dependent memory and hippocampal long-term potentiation and neurogenesis in a mouse model of Rett syndrome, suggesting that DBS, which is already used in the treatment of several neurological conditions, could be a viable approach to mitigating cognitive impairment in Rett syndrome and other disorders of childhood intellectual disability.

doi: 10.1038/nature15694

Encoding of action by the Purkinje cells of the cerebellum p.439

Recording from Purkinje cells in monkeys, this study found that the combined simple-spike responses of bursting and pausing Purkinje cells, but not either population alone, predicted the real-time speed of saccades; moreover, when Purkinje cells were organized according to their complex-spike field, the population responses encoded both speed and direction of the eye during saccades via a gain field.

doi: 10.1038/nature15693

η-Secretase processing of APP inhibits neuronal activity in the hippocampus p.443

Alzheimer disease (AD) is characterized by the accumulation of amyloid plaques, which are predominantly composed of amyloid-β peptide. Two principal physiological pathways either prevent or promote amyloid-β generation from its precursor, β-amyloid precursor protein (APP), in a competitive manner. Although APP processing has been studied in great detail, unknown proteolytic events seem to hinder stoichiometric analyses of APP metabolism in vivo. Here we describe a new physiological APP processing pathway, which generates proteolytic fragments capable of inhibiting neuronal activity within the hippocampus. We identify higher molecular mass carboxy-terminal fragments (CTFs) of APP, termed CTF-η, in addition to the long-known CTF-α and CTF-β fragments generated by the α- and β-secretases ADAM10 (a disintegrin and metalloproteinase 10) and BACE1 (β-site APP cleaving enzyme 1), respectively. CTF-η generation is mediated in part by membrane-bound matrix metalloproteinases such as MT5-MMP, referred to as η-secretase activity. η-Secretase cleavage occurs primarily at amino acids 504–505 of APP695, releasing a truncated ectodomain. After shedding of this ectodomain, CTF-η is further processed by ADAM10 and BACE1 to release long and short Aη peptides (termed Aη-α and Aη-β). CTFs produced by η-secretase are enriched in dystrophic neurites in an AD mouse model and in human AD brains. Genetic and pharmacological inhibition of BACE1 activity results in robust accumulation of CTF-η and Aη-α. In mice treated with a potent BACE1 inhibitor, hippocampal long-term potentiation was reduced. Notably, when recombinant or synthetic Aη-α was applied on hippocampal slices ex vivo, long-term potentiation was lowered. Furthermore, in vivo single-cell two-photon calcium imaging showed that hippocampal neuronal activity was attenuated by Aη-α. These findings not only demonstrate a major functionally relevant APP processing pathway, but may also indicate potential translational relevance for therapeutic strategies targeting APP processing.

doi: 10.1038/nature14864

Alternative transcription initiation leads to expression of a novel ALK isoform in cancer p.453

A novel ALK transcript expressed in a subset of human cancers, arising from a de novo alternative transcription initiation site within the ALK gene, is described; the ALK transcript encodes three protein isoforms that stimulate tumorigenesis in vivo in mouse models; resultant tumours are sensitive to treatments with ALK inhibitors, indicating a possible therapeutic avenue for patients expressing these isoforms.

doi: 10.1038/nature15258