Volume 497 Issue 7448


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

The cleaner state p.157

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

doi: 10.1038/497157b

Voice of Pro-Test p.158

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

doi: 10.1038/497158a


News Features

The genome hacker p.172

Yaniv Erlich shows how research participants can be identified from 'anonymous' DNA.

doi: 10.1038/497172a

News & Views

Exotic pear-shaped nuclei p.190

The elusive pear shapes of certain nuclei, which are challenging to predict theoretically, have at last been measured precisely. Two experts offer their views on what the results mean for nuclear physics and particle physics. See Article p.199

doi: 10.1038/497190a

The cosmic web in focus p.191

Detection of the trace neutral fraction of hydrogen gas that stretches between the nearby Andromeda and Triangulum galaxies has allowed resolved spectral imaging of this elusive intergalactic medium. See Letter p.224

doi: 10.1038/497191a

Security measures of a master regulator p.193

At last, the crystal structure is revealed for the catalytically active mTOR kinase enzyme, a master regulator of cell growth. The structure indicates a gatekeeper mechanism that controls substrate access to the active site. See Article p.217

doi: 10.1038/nature12101

Memory cells sound the alarm p.194

In a finding that could have implications for vaccine design, memory immune cells at mucosal surfaces have been shown to respond to encounters with pathogens by issuing signals that recruit other memory cells to the site.

doi: 10.1038/497194b

Death brings new life to muscle p.196

Fusion of muscle cells called myoblasts underlies the generation and maintenance of skeletal muscle throughout an animal's life. Emerging data indicate that cell death acts as a signal to enhance these processes in mammals. See Letter p.263

doi: 10.1038/nature12097

Inflammation links ageing to the brain p.197

Inflammation-activated signalling pathways in the brain's hypothalamus control the production of ageing-related hormones. This finding provides a link between inflammation, stress responses and systemic ageing. See Article p.211

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


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

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

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

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