Right to remain silent p.157

doi: 10.1038/497157a

The cleaner state p.157

doi: 10.1038/497157b

Voice of Pro-Test p.158

doi: 10.1038/497158a

US warheads to get a facelift p.165

doi: 10.1038/497165a

Oceans under surveillance p.167

doi: 10.1038/497167a

US bill would keep helium store afloat p.168

doi: 10.1038/497168a

Symmetry study deemed a fraud p.170

doi: 10.1038/497170a

The genome hacker p.172

doi: 10.1038/497172a

Once more, with feeling p.176

doi: 10.1038/497176a

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

doi: 10.1038/nature12082

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

doi: 10.1038/nature12012

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

doi: 10.1038/nature12023

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

doi: 10.1038/nature12068

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

doi: 10.1038/nature12026

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

doi: 10.1038/nature12119

Meis1 regulates postnatal cardiomyocyte cell cycle arrest p.249

doi: 10.1038/nature12054

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

doi: 10.1038/nature12048

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

doi: 10.1038/nature12079

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

doi: 10.1038/nature12135

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

doi: 10.1038/nature12046

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

doi: 10.1038/nature12045