Volume 497 Number 7448



The cleaner state p.157

Federal regulators could learn much from California’s low-carbon fuel programme.

doi: 10.1038/497157b


Right to remain silent p.157

The US Supreme Court should overturn the 2003 law that requires federally funded HIV/AIDS programmes abroad to denounce prostitution.

doi: 10.1038/497157a


Voice of Pro-Test p.158

Confidence is rising among scientists defending animal research. It should be encouraged.

doi: 10.1038/497158a



US warheads to get a facelift p.165

Obama boosts ‘stockpile stewardship’ funds at energy labs.

doi: 10.1038/497165a


Oceans under surveillance p.167

Three projects seek to track changes in Atlantic overturning circulation currents.

doi: 10.1038/497167a


US bill would keep helium store afloat p.168

Russia and Qatar prepare to dominate market as gas price inflation puts researchers under pressure.

doi: 10.1038/497168a


Symmetry study deemed a fraud p.170

University finds evidence of fakery in Jamaican dance data.

doi: 10.1038/497170a

News Features


Privacy protections: The genome hacker p.172


doi: 10.1038/497172a


Neuroprosthetics: Once more, with feeling p.176


doi: 10.1038/497176a

News & Views


Exotic pear-shaped nuclei p.190


doi: 10.1038/497190a


The cosmic web in focus p.191


doi: 10.1038/497191a


Security measures of a master regulator p.193


doi: 10.1038/nature12101


Memory cells sound the alarm p.194


doi: 10.1038/497194b


Death brings new life to muscle p.196


doi: 10.1038/nature12097


Inflammation links ageing to the brain p.197


doi: 10.1038/nature12100



Studies of pear-shaped nuclei using accelerated radioactive beams p.199

There is strong circumstantial evidence that certain heavy, unstable atomic nuclei are ‘octupole deformed’, that is, distorted into a pear shape. This contrasts with the more prevalent rugby-ball shape of nuclei with reflection-symmetric, quadrupole deformations. The elusive octupole deformed nuclei are of importance for nuclear structure theory, and also in searches for physics beyond the standard model; any measurable electric-dipole moment (a signature of the latter) is expected to be amplified in such nuclei. Here we determine electric octupole transition strengths (a direct measure of octupole correlations) for short-lived isotopes of radon and radium. Coulomb excitation experiments were performed using accelerated beams of heavy, radioactive ions. Our data on 220Rn and 224Ra show clear evidence for stronger octupole deformation in the latter. The results enable discrimination between differing theoretical approaches to octupole correlations, and help to constrain suitable candidates for experimental studies of atomic electric-dipole moments that might reveal extensions to the standard model.

doi: 10.1038/nature12073


Hierarchy of orofacial rhythms revealed through whisking and breathing p.205

Whisking and sniffing are predominant aspects of exploratory behaviour in rodents. Yet the neural mechanisms that generate and coordinate these and other orofacial motor patterns remain largely uncharacterized. Here we use anatomical, behavioural, electrophysiological and pharmacological tools to show that whisking and sniffing are coordinated by respiratory centres in the ventral medulla. We delineate a distinct region in the ventral medulla that provides rhythmic input to the facial motor neurons that drive protraction of the vibrissae. Neuronal output from this region is reset at each inspiration by direct input from the pre-Bötzinger complex, such that high-frequency sniffing has a one-to-one relationship with whisking, whereas basal respiration is accompanied by intervening whisks that occur between breaths. We conjecture that the respiratory nuclei, which project to other premotor regions for oral and facial control, function as a master clock for behaviours that coordinate with breathing.

doi: 10.1038/nature12076


Hypothalamic programming of systemic ageing involving IKK-β, NF-κB and GnRH p.211

Ageing is a result of gradual and overall functional deteriorations across the body; however, it is unknown whether an individual tissue primarily works to mediate the ageing progress and control lifespan. Here we show that the hypothalamus is important for the development of whole-body ageing in mice, and that the underlying basis involves hypothalamic immunity mediated by IκB kinase-β (IKK-β), nuclear factor κB (NF-κB) and related microglia–neuron immune crosstalk. Several interventional models were developed showing that ageing retardation and lifespan extension are achieved in mice by preventing ageing-related hypothalamic or brain IKK-β and NF-κB activation. Mechanistic studies further revealed that IKK-β and NF-κB inhibit gonadotropin-releasing hormone (GnRH) to mediate ageing-related hypothalamic GnRH decline, and GnRH treatment amends ageing-impaired neurogenesis and decelerates ageing. In conclusion, the hypothalamus has a programmatic role in ageing development via immune–neuroendocrine integration, and immune inhibition or GnRH restoration in the hypothalamus/brain represent two potential strategies for optimizing lifespan and combating ageing-related health problems.

doi: 10.1038/nature12143


mTOR kinase structure, mechanism and regulation p.217

The mammalian target of rapamycin (mTOR), a phosphoinositide 3-kinase-related protein kinase, controls cell growth in response to nutrients and growth factors and is frequently deregulated in cancer. Here we report co-crystal structures of a complex of truncated mTOR and mammalian lethal with SEC13 protein 8 (mLST8) with an ATP transition state mimic and with ATP-site inhibitors. The structures reveal an intrinsically active kinase conformation, with catalytic residues and a catalytic mechanism remarkably similar to canonical protein kinases. The active site is highly recessed owing to the FKBP12–rapamycin-binding (FRB) domain and an inhibitory helix protruding from the catalytic cleft. mTOR-activating mutations map to the structural framework that holds these elements in place, indicating that the kinase is controlled by restricted access. In vitro biochemistry shows that the FRB domain acts as a gatekeeper, with its rapamycin-binding site interacting with substrates to grant them access to the restricted active site. Rapamycin–FKBP12 inhibits the kinase by directly blocking substrate recruitment and by further restricting active-site access. The structures also reveal active-site residues and conformational changes that underlie inhibitor potency and specificity.

doi: 10.1038/nature12122



Discrete clouds of neutral gas between the galaxies M31 and M33 p.224

About half of the gas stretching between the galaxies M31 and M33 is shown to be composed of clouds, with the rest distributed in an extended, diffuse component.

doi: 10.1038/nature12082


Bell violation using entangled photons without the fair-sampling assumption p.227

The fair-sampling loophole is closed in a Bell inequality violation experiment with entangled photons, making the photon the first physical system for which all the main loopholes have been closed.

doi: 10.1038/nature12012


Formation of a topological non-Fermi liquid in MnSi p.231

The non-Fermi-liquid regime that emerges in MnSi under high pressures displays a Hall signal that can be traced to topologically non-trivial spin configurations at low pressures — a well-understood skyrmion lattice — empirically suggesting a route towards a breakdown of Fermi liquid theory in pure metals.

doi: 10.1038/nature12023


Future sea-level rise from Greenland’s main outlet glaciers in a warming climate p.235

A model of the four main outlet glaciers that drain the Greenland Ice Sheet predicts that they will contribute 19 to 30 millimetres to sea-level rise by 2200 in a mid-range future warming scenario, and 29 to 49 millimetres in a more extreme scenario.

doi: 10.1038/nature12068


M-CSF instructs myeloid lineage fate in single haematopoietic stem cells p.239

M-CSF, a myeloid cytokine released during infection and inflammation, instructs myeloid lineage fate in single haematopoietic stem cells by directly inducing PU.1, a known myeloid lineage master regulator; this shows that specific cytokines can act directly on haematopoietic stem cells to instruct a change of cell identity.

doi: 10.1038/nature12026


A role for the Perlman syndrome exonuclease Dis3l2 in the Lin28–let-7 pathway p.244

This study shows that Dis3l2 is the 3′–5′ exonuclease that mediates the degradation of uridylated precursor let-7 microRNA; this is the first physiological RNA substrate identified for this new exonuclease, which causes the Perlman syndrome of fetal overgrowth and Wilms’ tumour susceptibility when mutated.

doi: 10.1038/nature12119


Meis1 regulates postnatal cardiomyocyte cell cycle arrest p.249

The neonatal heart has a high regenerative capacity that is lost in adult life; the transcription factor Meis1 has been identified as a relevant proliferative switch for this transition, providing a potential therapeutic target for adult heart regeneration.

doi: 10.1038/nature12054


A CRISPR/Cas system mediates bacterial innate immune evasion and virulence p.254

The CRISPR/Cas system known to aid bacterial defences by targeting invading DNA can also act to evade eukaryotic defences through a different class of small RNAs downregulating an endogenous immunogenic bacterial lipoprotein.

doi: 10.1038/nature12048


Thymus-derived regulatory T cells contribute to tolerance to commensal microbiota p.258

By using high-throughput sequencing of T-cell receptors, this study shows that thymus-derived regulatory T (Treg) cells constitute most Treg cells in all lymphoid and intestinal organs, including the colon, suggesting that thymic Treg cells and not induced Treg cells dominantly control tolerance to the gut’s antigens such as commensal microbiota.

doi: 10.1038/nature12079


Phosphatidylserine receptor BAI1 and apoptotic cells as new promoters of myoblast fusion p.263

The apoptotic event of phosphatidylserine exposure and its recognition by the receptor BAI1 has an unexpected new role as a signal enhancing mouse myoblast fusion, an insight with relevance to some congenital muscle diseases and muscle injury treatments.

doi: 10.1038/nature12135

構造生物学:Lactobacillus brevis由来の葉酸エネルギー共役因子輸送体の結晶構造

Crystal structure of a folate energy-coupling factor transporter from Lactobacillus brevis p.268

The crystal structure of an inward-facing, nucleotide-free folate energy-coupling factor transporter from Lactobacillus brevis at a resolution of 3 Å suggests a transport model that involves a substantial conformational change of the substrate-specific binding protein, FolT.

doi: 10.1038/nature12046


Structure of a bacterial energy-coupling factor transporter p.272

The crystal structure of a nucleotide-free energy-coupling factor transporter from Lactobacillus brevis at a resolution of 3.5 Å suggests a plausible working model for the transport cycle of such transporters.

doi: 10.1038/nature12045

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