Volume 504 Number 7478


Call the cops p.7

The long arm of the law has reached into an investigation of alleged scientific misconduct in Italy, and should perhaps stretch still farther.

doi: 10.1038/504007a

The FDA and me p.7

Medical testing firms find it is in their best interests to cooperate with regulators.

doi: 10.1038/504007b

Lecture notes p.8

A physics course that hooked a generation reminds us that teachers need support.

doi: 10.1038/504008a


Iran hit by drug shortage p.15

Sanctions cause increasing shortfall in medicines and vaccines.

doi: 10.1038/504015a

Hominin DNA baffles experts p.16

Analysis of oldest sequence from a human ancestor suggests link to mystery population.

doi: 10.1038/504016a

Image search triggers Italian police probe p.18

Method for checking global literature leads to investigation of cancer researcher.

doi: 10.1038/504018a

Bacteria evade detection net p.19

Slothful response from regulators and manufacturers means antibiotic resistance is missed.

doi: 10.1038/504019a

Museums hunt for relics from genomics’ early days p.20

Collectors band together to salvage cast-off equipment.

doi: 10.1038/504020a

News Features

Global health: One million deaths p.22

What researchers are learning from an unprecedented survey of mortality in India.

doi: 10.1038/504022a

Geology: North America's broken heart p.24

A billion years ago, a huge rift nearly cleaved North America down the middle. And then it failed. Researchers may be getting close to finding out why.

doi: 10.1038/504024a

News & Views

Planetary science: Shadows cast on Moon's origin p.90

Our knowledge of how Earth's natural satellite formed is increasingly being challenged by observations and computer simulations. Two scientists outline our current understanding from the point of view of the satellite's geochemistry and its early dynamical history.

doi: 10.1038/504090a

Stem cells: Dual response to Ras mutation p.91

Proliferation-driving mutations in haematopoietic stem cells often result in the loss of stem-cell properties. But at least one common oncogenic mutation seems to enhance both proliferation and stem-cell self-renewal. See Letter p.143

doi: 10.1038/nature12840

Astrophysics: Magnetic fields in γ-ray bursts p.92

Observations of a high degree of polarization in the immediate optical afterglow of a γ-ray burst indicate that these powerful cosmic explosions carry large-scale, ordered magnetic fields. See Letter p.119

doi: 10.1038/504092a

Structural biology: Ion channel seen by electron microscopy p.93

Structures of the heat-sensitive TRPV1 ion channel have been solved using single-particle electron cryo-microscopy, representing a landmark in the use of this technique for structural biology. See Articles p.107 & p.113

doi: 10.1038/504093a

Nobel 2013: Chemistry: Methods for computational chemistry p.96

doi: 10.1038/504096a

Nobel 2013: Economics: Predicting asset prices p.97

doi: 10.1038/504097a

Nobel 2013: Physiology or medicine: Traffic control system within cells p.98

doi: 10.1038/504098a

Nobel 2013: Physics: Endowing particles with mass p.99

doi: 10.1038/504099a


Activation and allosteric modulation of a muscarinic acetylcholine receptor p.101

Very little is known about how a G-protein-coupled receptor (GPCR) transitions from an inactive to an active state, but this study has solved the X-ray crystal structures of the human M2 muscarinic acetylcholine receptor bound to a high-affinity agonist in an active state and to a high-affinity agonist and a small-molecule allosteric modulator in an active state; the structures provide insights into the activation mechanism and allosteric modulation of muscarinic receptors.

doi: 10.1038/nature12735

Structure of the TRPV1 ion channel determined by electron cryo-microscopy p.107

A high-resolution electron cryo-microscopy structure of the rat transient receptor potential (TRP) channel TRPV1 in its ‘closed’ state is presented; the overall structure of this ion channel is found to share some common features with voltage-gated ion channels, although several unique, TRP-specific features are also characterized.

doi: 10.1038/nature12822

TRPV1 structures in distinct conformations reveal activation mechanisms p.113

Using a peptide toxin and small vanilloid agonists as pharmacological probes, high-resolution electron cryo-microscopy structures of rat TRPV1–ligand complexes are solved; these structures highlight conformational differences between TRP and voltage-gated ion channels in their active states, and suggest a dual gating mechanism that may account for the ability of members of the TRP channel superfamily to integrate diverse physiological signals.

doi: 10.1038/nature12823


Highly polarized light from stable ordered magnetic fields in GRB 120308A p.119

The immediate optical afterglow of the γ-ray burst GRB 120308A is highly polarized, showing that γ-ray bursts contain magnetized baryonic jets with large-scale uniform fields that can survive long after the initial explosion.

doi: 10.1038/nature12814

Olivine in an unexpected location on Vesta’s surface p.122

Although olivine was expected to occur within the deep, south-pole basins of asteroid Vesta, which are thought to be excavated mantle rocks, spectral data from NASA’s Dawn spacecraft show that it instead occurs as near-surface materials in Vesta’s northern hemisphere.

doi: 10.1038/nature12665

Late-twentieth-century emergence of the El Niño propagation asymmetry and future projections p.126

The El Niño propagation asymmetry (in which sea surface temperature anomalies propagate eastwards during an extreme El Niño event) is shown to be caused by the variations in upper ocean currents in the equatorial Pacific Ocean; increased occurrences of the propagation asymmetry may be a manifestation of global greenhouse warming.

doi: 10.1038/nature12683

Foundering of lower island-arc crust as an explanation for the origin of the continental Moho p.131

The calculated density and seismic structure of the two best-exposed island arc sections (Kohistan and Talkeetna) reveals that the foundering of the lower arc crust produces a sharp seismic discontinuity characteristic of the continental Mohorovičić discontinuity.

doi: 10.1038/nature12758

Genetic incompatibilities are widespread within species p.135

The role that epistasis — non-additive interactions between alleles — plays in shaping population fitness is investigated in Drosophila melanogaster; the raw material to drive reproductive isolation is found to be segregating contemporaneously within species and does not necessarily require the emergence of incompatible mutations independently derived and fixed in allopatry.

doi: 10.1038/nature12678

A melanocyte lineage program confers resistance to MAP kinase pathway inhibition p.138

Expression of more than 15,500 genes individually in a melanoma cell line treated with RAF, MEK, ERK or combined RAF–MEK inhibitors reveals a cyclic-AMP-dependent melanocytic signalling network associated with drug resistance; this may represent a novel therapeutic target for melanoma treatment.

doi: 10.1038/nature12688

Oncogenic Nras has bimodal effects on stem cells that sustainably increase competitiveness p.143

Oncogenic Nras in mouse haematopoietic stem cells can increase the probability of cell division in some cells and decrease it in others; this bimodal activity explains how this single pre-leukaemic mutation can increase proliferation without reducing competitiveness by clonally expanding the rapidly dividing cell population and also promoting long-term self-renewal of stem cells.

doi: 10.1038/nature12830

The protein quality control system manages plant defence compound synthesis p.148

Plants defend themselves against attackers by producing bioactive secondary metabolites such as triterpene saponins; here, the endoplasmic-reticulum-associated degradation (ERAD) system is shown to control the activity of HMGR, the rate-limiting enzyme in the supply of the terpene precursor isopentenyl diphosphate, thereby preventing unrestrained saponin production and ensuring the integrity of plant development.

doi: 10.1038/nature12685

Histone deacetylase 3 coordinates commensal-bacteria-dependent intestinal homeostasis p.153

This work identifies a role for intestinal epithelial cell (IEC)-intrinsic expression of histone deacetylase 3 in regulating commensal-bacteria-dependent gene expression and intestinal homeostasis; IEC-specific HDAC3 deficiency gives rise to Paneth cell abnormalities, impaired intestinal barrier function, and increased DSS-induced intestinal inflammation in commensal-bacteria-containing, but not germ-free, mice.

doi: 10.1038/nature12687

Immunosuppressive CD71+ erythroid cells compromise neonatal host defence against infection p.158

In neonatal mice, susceptibility to infection is due to an enriched subset of arginase-2-expressing CD71+ erythroid cells, which suppresses the systemic activation of immune cells, thereby protecting neonates against aberrant inflammation triggered by colonization with commensal microbes.

doi: 10.1038/nature12675

EHMT1 controls brown adipose cell fate and thermogenesis through the PRDM16 complex p.163

Brown adipose tissue-enriched lysine methyltransferase EHMT1 is an essential enzyme in the PRDM16–C/EBP-β transcriptional complex that controls brown adipose cell fate and energy metabolism.

doi: 10.1038/nature12652

Structural basis for the modular recognition of single-stranded RNA by PPR proteins p.168

Although the roles of pentatricopeptide repeat (PPR) proteins in RNA metabolism are well characterised, the mechanism by which they recognise specific single-stranded (ss)RNAs remains ill-understood; here X-ray crystal structures of maize PPR10 in the presence and absence of ssRNA provide details of the PPR10–ssRNA interaction.

doi: 10.1038/nature12651

Structure of LIMP-2 provides functional insights with implications for SR-BI and CD36 p.172

These results reveal the first high-resolution structural analysis of LIMP-2 and, by homology modelling, the structure of SR-BI and CD36, members of the CD36 superfamily of scavenger receptor proteins.

doi: 10.1038/nature12684

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