Volume 511 Issue 7508

Editorials

Brain fog p.125

The criticism of Europe’s Human Brain Project by leading scientists reflects a messy management structure that is in urgent need of clear direction.

doi: 10.1038/511125a

Be concerned p.126

A possible link between neonicotinoid pesticide use and a decline in bird numbers is worrying.

doi: 10.1038/511126b

Barriers to trust p.126

An outbreak of Ebola highlights the difficulties of implementing public-health measures.

doi: 10.1038/511126a

News

News Features

Cell-induced stress p.140

As a much-hailed breakthrough in stem-cell science unravelled this year, many have been asking: ‘Where were the safeguards?’

doi: 10.1038/511140a

The great mosquito hunt p.144

From dogs to balloons, researchers are using unorthodox ways to find out where malaria vectors hide during a long dry season.

doi: 10.1038/511144a

News & Views

How to control bovine tuberculosis p.158

A model of the transmission and spread of bovine tuberculosis in Britain suggests that controlling the epidemic will require large-scale cattle slaughter or a major rethink of combined control strategies. See Letter p.228

doi: 10.1038/nature13514

A new view on displays p.159

Materials that rapidly switch between amorphous and crystalline states are widely used to manage heat and store data. They now emerge as promising building blocks for ultrahigh-resolution display devices. See Letter p.206

doi: 10.1038/511159a

The quest for the perfect reprogrammed cell p.160

There are two methods for reprogramming mature cells to pluripotent stem cells, which can give rise to all cells of the body. The first direct comparison of the methods reveals that both can cause subtle molecular defects. See Article p.177

doi: 10.1038/nature13515

A structure to remember p.162

NMDA receptors are crucial in the workings of the brain and in its disorders. Two structures of almost complete receptors reveal the intricate complexity of these large, multi-domain molecular machines. See Article p.191

doi: 10.1038/511162a

Fingerprints of a trace nutrient p.164

Lack of dissolved iron in the sea limits biological productivity and the uptake of carbon dioxide. The sources of dissolved iron in the North Atlantic Ocean have been identified from isotopic variations of this trace nutrient. See Letter p.212

doi: 10.1038/nature13513

A caring majority secures the future p.165

An experiment studying people's willingness to sacrifice personal gains so that resources are passed to future generations shows that this occurs only when extractions by free-riders are curbed by majority rule. See Letter p.220

doi: 10.1038/nature13510

Review

Metabolism of stromal and immune cells in health and disease p.167

Cancer cells have been at the centre of cell metabolism research, but the metabolism of stromal and immune cells has received less attention. Nonetheless, these cells influence the progression of malignant, inflammatory and metabolic disorders. Here we discuss the metabolic adaptations of stromal and immune cells in health and disease, and highlight how metabolism determines their differentiation and function.

doi: 10.1038/nature13312

Articles

Abnormalities in human pluripotent cells due to reprogramming mechanisms p.177

Genome-wide analysis of matched human IVF embryonic stem cells (IVF ES cells), induced pluripotent stem cells (iPS cells) and nuclear transfer ES cells (NT ES cells) derived by somatic cell nuclear transfer (SCNT) reveals that human somatic cells can be faithfully reprogrammed to pluripotency by SCNT; NT ES cells and iPS cells derived from the same somatic cells contain comparable numbers of de novo copy number variations, but whereas DNA methylation and transcriptome profiles of NT ES cells and IVF ES cells are similar, iPS cells have residual patterns typical of parental somatic cells.

doi: 10.1038/nature13551

Aryl hydrocarbon receptor control of a disease tolerance defence pathway p.184

Initial exposure to lipopolysaccharide (LPS) induces endotoxin tolerance, which reduces immunological reactions to LPS; here it is shown that primary LPS challenge is controlled by AhR, TDO2 and IL-10, whereas sustained effects require AhR, IDO1 and TGF-β, allowing for disease tolerance with reduced immunopathology in infections.

doi: 10.1038/nature13323

NMDA receptor structures reveal subunit arrangement and pore architecture p.191

X-ray crystal structures are presented of the N-methyl-d-aspartate (NMDA) receptor, a calcium-permeable ion channel that opens upon binding of glutamate and glycine; glutamate is a key excitatory neurotransmitter and enhanced structural insight of this receptor may aid development of therapeutic small molecules.

doi: 10.1038/nature13548

Letters

Strong contributions of local background climate to urban heat islands p.216

Climate modelling is used to show that for cities across North America, geographic variations in daytime urban heat islands—that is, the temperature differences between urban and adjacent rural areas—are largely explained by variations in the efficiency with which those areas convect heat to the lower atmosphere.

doi: 10.1038/nature13462

Cooperating with the future p.220

An intergenerational cooperation game has been developed to study decision-making regarding resource use: when decisions about resource extraction were made individually the resource was rapidly depleted by a minority of defectors; the resource was sustainably maintained across generations, however, when decisions were made democratically by voting.

doi: 10.1038/nature13530

Amphibians acquire resistance to live and dead fungus overcoming fungal immunosuppression p.224

The fungal pathogen Batrachochytrium dendrobatidis has been implicated in the decline of a large number of amphibian species; here it is shown that frogs can learn to avoid the pathogen, acquire resistance to it and be immunized against it using dead pathogen, findings that potentially offer a way in which resistant populations could be reintroduced into areas that have seen catastrophic declines.

doi: 10.1038/nature13491

A dynamic model of bovine tuberculosis spread and control in Great Britain p.228

Bovine tuberculosis is a major economic burden on the cattle industry, and attempts to control it have been politically controversial; here farm movement and bovine tuberculosis incidence data are used to construct a mechanistic model and tease apart the factors contributing to epidemic bovine tuberculosis spread.

doi: 10.1038/nature13529

Cntnap4 differentially contributes to GABAergic and dopaminergic synaptic transmission p.236

The molecular relationship between synaptic dysfunction and psychiatric disorders was investigated using a mouse model system; presynaptically localized Cntnap4 is required for the output of two disease-relevant neuronal subpopulations (cortical parvalbumin-positive GABAergic cells and midbrain dopaminergic neurons) and Cntnap4 mutants show behavioural abnormalities which can be pharmacologically reversed.

doi: 10.1038/nature13248

Novel somatic and germline mutations in intracranial germ cell tumours p.241

Intracranial germ cell tumours are rare tumours affecting mainly male adolescents, mainly in Asia; here the authors identify frequent mutations in the KIT/RAS and AKT/mTOR signalling pathways as well as rare germline variants in JMJD1C, suggesting potential therapeutic strategies focusing on the inhibition of KIT/RAS activation and the AKT1/mTOR pathway.

doi: 10.1038/nature13296

Avoidance of ribonucleotide-induced mutations by RNase H2 and Srs2-Exo1 mechanisms p.251

Srs2 helicase is known to dismantle nucleofilaments of Rad51 recombinase to prevent spurious recombination events and unwind trinucleotide sequences that are prone to hairpin formation. Here we document a new, unexpected genome maintenance role of Srs2 in the suppression of mutations arising from mis-insertion of ribonucleoside monophosphates during DNA replication. In cells lacking RNase H2, Srs2 unwinds DNA from the 5′ side of a nick generated by DNA topoisomerase I at a ribonucleoside monophosphate residue. In addition, Srs2 interacts with and enhances the activity of the nuclease Exo1, to generate a DNA gap in preparation for repair. Srs2–Exo1 thus functions in a new pathway of nick processing-gap filling that mediates tolerance of ribonucleoside monophosphates in the genome. Our results have implications for understanding the basis of Aicardi–Goutières syndrome, which stems from inactivation of the human RNase H2 complex.

doi: 10.1038/nature13292