Volume 510 Number 7505

Editorials

Present danger p.311

There is much hype about predicting and preventing future pandemics, but not enough is being done about a threat sitting under our noses.

doi: 10.1038/510311a

Summer skills p.312

A fledgling neuroscience programme is a rare beacon of research excellence in Romania.

doi: 10.1038/510312b

Quanundrum p.312

Does reality exist? Fifty years on, Bell’s theorem still divides (and confuses) physicists.

doi: 10.1038/510312a

News

HIV trial attacked p.324

Critics question ethics of allowing pregnant women to receive treatment that falls below the standard in their country.

doi: 10.1038/510324a

News Features

Water on tap p.326

Researchers are exploring unconventional sources of fresh water to quench the globe's growing thirst.

doi: 10.1038/510326a

The inside track p.330

Members of the US National Academy of Sciences have long enjoyed a privileged path to publication in the body's prominent house journal. Meet the scientists who use it most heavily.

doi: 10.1038/510330a

News & Views

Natural-born killers unleashed p.342

The finding that phosphoinositide-3-OH kinase δ restrains the antitumour immune response by promoting the action of suppressive immune cells may broaden the applicability of drugs targeting this enzyme to multiple cancers. See Letter p.407

doi: 10.1038/nature13503

How chaos forgets and remembers p.343

“It is difficult to make predictions, especially about the future,” goes the proverb. A study of the dynamics of chaotic systems in the context of information theory adds a twist to this saying.

doi: 10.1038/510343a

Immaturity in the gut microbial community p.344

Undernourished children fall behind not only on growth, but also on maturation of their intestinal bacterial communities, according to a study comparing acutely malnourished and healthy Bangladeshi children. See Letter p.417

doi: 10.1038/nature13347

Powered by magic p.345

What gives quantum computers that extra oomph over their classical digital counterparts? An intrinsic, measurable aspect of quantum mechanics called contextuality, it now emerges. See Article p.351

doi: 10.1038/nature13504

Balancing act p.347

The enzyme parkin is known to promote disposal of organelles called mitochondria that have suffered damage. The identification of an enzyme that opposes parkin demonstrates how a delicate balance is maintained in the cell. See Article p.370

doi: 10.1038/nature13500

Feel the force p.349

An approach based on quantum sensing, in which controlled quantum systems serve as precision sensors, has enabled measurement of the weak magnetic interaction between two electrons bound to two separate ions. See Letter p.376

doi: 10.1038/510349a

Articles

Contextuality supplies the ‘magic’ for quantum computation p.351

Quantum computing promises advantages over classical computing for certain problems; now ‘quantum contextuality’ — a generalization of the concept of quantum non-locality — is shown to be a critical resource that gives the most promising class of quantum computers their power.

doi: 10.1038/nature13460

The genome of Eucalyptus grandis OPEN p.356

The Eucalyptus grandis genome has been sequenced, revealing the greatest number of tandem duplications of any plant genome sequenced so far, and the highest diversity of genes for specialized metabolites that act as chemical defence and provide unique pharmaceutical oils; genome sequencing of the sister species E. globules and a set of inbred E. grand is tree genomes reveals dynamic genome evolution and hotspots of inbreeding depression.

doi: 10.1038/nature13308

The mitochondrial deubiquitinase USP30 opposes parkin-mediated mitophagy p.370

Damaged mitochondria are removed by mitophagy, and defects in mitophagy are linked to Parkinson’s disease; here it is shown that USP30, a deubiquitinase localized to mitochondria, antagonizes mitophagy by removing the ubiquitin tags put in place by Parkin, USP30 inhibition is therefore potentially beneficial for Parkinson’s disease by promoting mitochondrial clearance and quality control.

doi: 10.1038/nature13418

Letters

The metabolite α-ketoglutarate extends lifespan by inhibiting ATP synthase and TOR p.397

Metabolism and ageing are intimately linked. Compared with ad libitum feeding, dietary restriction consistently extends lifespan and delays age-related diseases in evolutionarily diverse organisms. Similar conditions of nutrient limitation and genetic or pharmacological perturbations of nutrient or energy metabolism also have longevity benefits. Recently, several metabolites have been identified that modulate ageing; however, the molecular mechanisms underlying this are largely undefined. Here we show that α-ketoglutarate (α-KG), a tricarboxylic acid cycle intermediate, extends the lifespan of adult Caenorhabditis elegans. ATP synthase subunit β is identified as a novel binding protein of α-KG using a small-molecule target identification strategy termed drug affinity responsive target stability (DARTS). The ATP synthase, also known as complex V of the mitochondrial electron transport chain, is the main cellular energy-generating machinery and is highly conserved throughout evolution. Although complete loss of mitochondrial function is detrimental, partial suppression of the electron transport chain has been shown to extend C. elegans lifespan. We show that α-KG inhibits ATP synthase and, similar to ATP synthase knockdown, inhibition by α-KG leads to reduced ATP content, decreased oxygen consumption, and increased autophagy in both C. elegans and mammalian cells. We provide evidence that the lifespan increase by α-KG requires ATP synthase subunit β and is dependent on target of rapamycin (TOR) downstream. Endogenous α-KG levels are increased on starvation and α-KG does not extend the lifespan of dietary-restricted animals, indicating that α-KG is a key metabolite that mediates longevity by dietary restriction. Our analyses uncover new molecular links between a common metabolite, a universal cellular energy generator and dietary restriction in the regulation of organismal lifespan, thus suggesting new strategies for the prevention and treatment of ageing and age-related diseases.

doi: 10.1038/nature13264

PTEN action in leukaemia dictated by the tissue microenvironment p.402

A mouse model of T-cell leukaemia is used to test whether PTEN loss is required for tumour maintenance as well as initiation; although it had little effect on tumour load in haematopoietic organs, PTEN reactivation reduced the CCR9-dependent tumour dissemination to the intestine that was amplified on PTEN loss, exposing the importance of tumour microenvironment in PTEN-deficient settings.

doi: 10.1038/nature13239

Persistent gut microbiota immaturity in malnourished Bangladeshi children p.417

Bacterial species whose representation defines healthy postnatal assembly of the gut microbiota in Bangladeshi children during their first 2 years are identified, and a model is constructed to compare healthy children to those with severe acute malnutrition (SAM); results show that SAM is associated with microbiota immaturity that is only partially ameliorated by existing nutritional interventions.

doi: 10.1038/nature13421