Look back in wonder p.149

doi: 10.1038/508149a

Political science p.149

doi: 10.1038/508149b

Copper rewired p.150

doi: 10.1038/508150a

NIH stem-cell programme closes p.157

doi: 10.1038/508157a

Metabolic quirks yield tumour hope p.158

doi: 10.1038/508158a

E-cigarettes affect cells p.159

doi: 10.1038/508159a

Earth observation enters next phase p.160

doi: 10.1038/508160a

Funders punish open-access dodgers p.161

doi: 10.1038/508161a

Western science severs ties with Russia p.162

doi: 10.1038/508162a

Time running out for rarest primate p.163

doi: 10.1038/508163a

Holding back the tide p.164

doi: 10.1038/508164a

The clock-watcher p.168

doi: 10.1038/508168a

Cracking up on asteroids p.190

doi: 10.1038/nature13222

Damage prevention targeted p.191

doi: 10.1038/nature13221

Africa's greenhouse-gas budget is in the red p.192

doi: 10.1038/508192a

Targeting a fat-accumulation gene p.194

doi: 10.1038/508194a

A strong hybrid couple p.195

doi: 10.1038/508195a

The purple heart of photosynthesis p.196

doi: 10.1038/nature13219

Transcriptional landscape of the prenatal human brain p.199

doi: 10.1038/nature13185

A mesoscale connectome of the mouse brain p.207

doi: 10.1038/nature13186

MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool p.215

doi: 10.1038/nature13181

Stereospecific targeting of MTH1 by (S)-crizotinib as an anticancer strategy p.222

doi: 10.1038/nature13194

Structure of the LH1–RC complex from Thermochromatium tepidum at 3.0 Å p.228

doi: 10.1038/nature13197

Thermal fatigue as the origin of regolith on small asteroids p.233

Space missions and thermal infrared observations have shown that small asteroids (kilometre-sized or smaller) are covered by a layer of centimetre-sized or smaller particles, which constitute the regolith. Regolith generation has traditionally been attributed to the fall back of impact ejecta and by the break-up of boulders by micrometeoroid impact. Laboratory experiments and impact models, however, show that crater ejecta velocities are typically greater than several tens of centimetres per second, which corresponds to the gravitational escape velocity of kilometre-sized asteroids. Therefore, impact debris cannot be the main source of regolith on small asteroids. Here we report that thermal fatigue, a mechanism of rock weathering and fragmentation with no subsequent ejection, is the dominant process governing regolith generation on small asteroids. We find that thermal fragmentation induced by the diurnal temperature variations breaks up rocks larger than a few centimetres more quickly than do micrometeoroid impacts. Because thermal fragmentation is independent of asteroid size, this process can also contribute to regolith production on larger asteroids. Production of fresh regolith originating in thermal fatigue fragmentation may be an important process for the rejuvenation of the surfaces of near-Earth asteroids, and may explain the observed lack of low-perihelion, carbonaceous, near-Earth asteroids.

doi: 10.1038/nature13153

A quantum gate between a flying optical photon and a single trapped atom p.237

The steady increase in control over individual quantum systems supports the promotion of a quantum technology that could provide functionalities beyond those of any classical device. Two particularly promising applications have been explored during the past decade: photon-based quantum communication, which guarantees unbreakable encryption but which still has to be scaled to high rates over large distances, and quantum computation, which will fundamentally enhance computability if it can be scaled to a large number of quantum bits (qubits). It was realized early on that a hybrid system of light qubits and matter qubits could solve the scalability problem of each field—that of communication by use of quantum repeaters, and that of computation by use of an optical interconnect between smaller quantum processors. To this end, the development of a robust two-qubit gate that allows the linking of distant computational nodes is “a pressing challenge”. Here we demonstrate such a quantum gate between the spin state of a single trapped atom and the polarization state of an optical photon contained in a faint laser pulse. The gate mechanism presented is deterministic and robust, and is expected to be applicable to almost any matter qubit. It is based on reflection of the photonic qubit from a cavity that provides strong light–matter coupling. To demonstrate its versatility, we use the quantum gate to create atom–photon, atom–photon–photon and photon–photon entangled states from separable input states. We expect our experiment to enable various applications, including the generation of atomic and photonic cluster states and Schrödinger-cat states, deterministic photonic Bell-state measurements, scalable quantum computation and quantum communication using a redundant quantum parity code.

doi: 10.1038/nature13177

Nanophotonic quantum phase switch with a single atom p.241

By analogy to transistors in classical electronic circuits, quantum optical switches are important elements of quantum circuits and quantum networks. Operated at the fundamental limit where a single quantum of light or matter controls another field or material system, such a switch may enable applications such as long-distance quantum communication, distributed quantum information processing and metrology, and the exploration of novel quantum states of matter. Here, by strongly coupling a photon to a single atom trapped in the near field of a nanoscale photonic crystal cavity, we realize a system in which a single atom switches the phase of a photon and a single photon modifies the atom’s phase. We experimentally demonstrate an atom-induced optical phase shift that is nonlinear at the two-photon level, a photon number router that separates individual photons and photon pairs into different output modes, and a single-photon switch in which a single ‘gate’ photon controls the propagation of a subsequent probe field. These techniques pave the way to integrated quantum nanophotonic networks involving multiple atomic nodes connected by guided light.

doi: 10.1038/nature13188

Dynamics of continental accretion p.245

Subduction zones become congested when they try to consume buoyant, exotic crust. The accretionary mountain belts (orogens) that form at these convergent plate margins have been the principal sites of lateral continental growth through Earth’s history. Modern examples of accretionary margins are the North American Cordilleras and southwest Pacific subduction zones. The geologic record contains abundant accretionary orogens, such as the Tasmanides, along the eastern margin of the supercontinent Gondwana, and the Altaïdes, which formed on the southern margin of Laurasia. In modern and ancient examples of long-lived accretionary orogens, the overriding plate is subjected to episodes of crustal extension and back-arc basin development, often related to subduction rollback and transient episodes of orogenesis and crustal shortening, coincident with accretion of exotic crust. Here we present three-dimensional dynamic models that show how accretionary margins evolve from the initial collision, through a period of plate margin instability, to re-establishment of a stable convergent margin. The models illustrate how significant curvature of the orogenic system develops, as well as the mechanism for tectonic escape of the back-arc region. The complexity of the morphology and the evolution of the system are caused by lateral rollback of a tightly arcuate trench migrating parallel to the plate boundary and orthogonally to the convergence direction. We find geological and geophysical evidence for this process in the Tasmanides of eastern Australia, and infer that this is a recurrent and global phenomenon.

doi: 10.1038/nature13033

Detection and replication of epistasis influencing transcription in humans p.249

Epistasis is the phenomenon whereby one polymorphism’s effect on a trait depends on other polymorphisms present in the genome. The extent to which epistasis influences complex traits and contributes to their variation is a fundamental question in evolution and human genetics. Although often demonstrated in artificial gene manipulation studies in model organisms, and some examples have been reported in other species, few examples exist for epistasis among natural polymorphisms in human traits. Its absence from empirical findings may simply be due to low incidence in the genetic control of complex traits, but an alternative view is that it has previously been too technically challenging to detect owing to statistical and computational issues. Here we show, using advanced computation and a gene expression study design, that many instances of epistasis are found between common single nucleotide polymorphisms (SNPs). In a cohort of 846 individuals with 7,339 gene expression levels measured in peripheral blood, we found 501 significant pairwise interactions between common SNPs influencing the expression of 238 genes (P < 2.91 × 10−16). Replication of these interactions in two independent data sets showed both concordance of direction of epistatic effects (P = 5.56 × 10−31) and enrichment of interaction P values, with 30 being significant at a conservative threshold of P < 9.98 × 10−5. Forty-four of the genetic interactions are located within 5 megabases of regions of known physical chromosome interactions (P = 1.8 × 10−10). Epistatic networks of three SNPs or more influence the expression levels of 129 genes, whereby one cis-acting SNP is modulated by several trans-acting SNPs. For example, MBNL1 is influenced by an additive effect at rs13069559, which itself is masked by trans-SNPs on 14 different chromosomes, with nearly identical genotype–phenotype maps for each cis–trans interaction. This study presents the first evidence, to our knowledge, for many instances of segregating common polymorphisms interacting to influence human traits.

doi: 10.1038/nature13005

A synchronized global sweep of the internal genes of modern avian influenza virus p.254

Zoonotic infectious diseases such as influenza continue to pose a grave threat to human health. However, the factors that mediate the emergence of RNA viruses such as influenza A virus (IAV) are still incompletely understood. Phylogenetic inference is crucial to reconstructing the origins and tracing the flow of IAV within and between hosts. Here we show that explicitly allowing IAV host lineages to have independent rates of molecular evolution is necessary for reliable phylogenetic inference of IAV and that methods that do not do so, including ‘relaxed’ molecular clock models, can be positively misleading. A phylogenomic analysis using a host-specific local clock model recovers extremely consistent evolutionary histories across all genomic segments and demonstrates that the equine H7N7 lineage is a sister clade to strains from birds—as well as those from humans, swine and the equine H3N8 lineage—sharing an ancestor with them in the mid to late 1800s. Moreover, major western and eastern hemisphere avian influenza lineages inferred for each gene coalesce in the late 1800s. On the basis of these phylogenies and the synchrony of these key nodes, we infer that the internal genes of avian influenza virus (AIV) underwent a global selective sweep beginning in the late 1800s, a process that continued throughout the twentieth century and up to the present. The resulting western hemispheric AIV lineage subsequently contributed most of the genomic segments to the 1918 pandemic virus and, independently, the 1963 equine H3N8 panzootic lineage. This approach provides a clear resolution of evolutionary patterns and processes in IAV, including the flow of viral genes and genomes within and between host lineages.

doi: 10.1038/nature13016

Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity p.258

In obesity and type 2 diabetes, Glut4 glucose transporter expression is decreased selectively in adipocytes. Adipose-specific knockout or overexpression of Glut4 alters systemic insulin sensitivity. Here we show, using DNA array analyses, that nicotinamide N-methyltransferase (Nnmt) is the most strongly reciprocally regulated gene when comparing gene expression in white adipose tissue (WAT) from adipose-specific Glut4-knockout or adipose-specific Glut4-overexpressing mice with their respective controls. NNMT methylates nicotinamide (vitamin B3) using S-adenosylmethionine (SAM) as a methyl donor. Nicotinamide is a precursor of NAD+, an important cofactor linking cellular redox states with energy metabolism. SAM provides propylamine for polyamine biosynthesis and donates a methyl group for histone methylation. Polyamine flux including synthesis, catabolism and excretion, is controlled by the rate-limiting enzymes ornithine decarboxylase (ODC) and spermidine–spermine N1-acetyltransferase (SSAT; encoded by Sat1) and by polyamine oxidase (PAO), and has a major role in energy metabolism. We report that NNMT expression is increased in WAT and liver of obese and diabetic mice. Nnmt knockdown in WAT and liver protects against diet-induced obesity by augmenting cellular energy expenditure. NNMT inhibition increases adipose SAM and NAD+ levels and upregulates ODC and SSAT activity as well as expression, owing to the effects of NNMT on histone H3 lysine 4 methylation in adipose tissue. Direct evidence for increased polyamine flux resulting from NNMT inhibition includes elevated urinary excretion and adipocyte secretion of diacetylspermine, a product of polyamine metabolism. NNMT inhibition in adipocytes increases oxygen consumption in an ODC-, SSAT- and PAO-dependent manner. Thus, NNMT is a novel regulator of histone methylation, polyamine flux and NAD+-dependent SIRT1 signalling, and is a unique and attractive target for treating obesity and type 2 diabetes.

doi: 10.1038/nature13198

ZMYND11 links histone H3.3K36me3 to transcription elongation and tumour suppression p.263

Recognition of modified histones by ‘reader’ proteins plays a critical role in the regulation of chromatin. H3K36 trimethylation (H3K36me3) is deposited onto the nucleosomes in the transcribed regions after RNA polymerase II elongation. In yeast, this mark in turn recruits epigenetic regulators to reset the chromatin to a relatively repressive state, thus suppressing cryptic transcription. However, much less is known about the role of H3K36me3 in transcription regulation in mammals. This is further complicated by the transcription-coupled incorporation of the histone variant H3.3 in gene bodies. Here we show that the candidate tumour suppressor ZMYND11 specifically recognizes H3K36me3 on H3.3 (H3.3K36me3) and regulates RNA polymerase II elongation. Structural studies show that in addition to the trimethyl-lysine binding by an aromatic cage within the PWWP domain, the H3.3-dependent recognition is mediated by the encapsulation of the H3.3-specific ‘Ser 31’ residue in a composite pocket formed by the tandem bromo–PWWP domains of ZMYND11. Chromatin immunoprecipitation followed by sequencing shows a genome-wide co-localization of ZMYND11 with H3K36me3 and H3.3 in gene bodies, and its occupancy requires the pre-deposition of H3.3K36me3. Although ZMYND11 is associated with highly expressed genes, it functions as an unconventional transcription co-repressor by modulating RNA polymerase II at the elongation stage. ZMYND11 is critical for the repression of a transcriptional program that is essential for tumour cell growth; low expression levels of ZMYND11 in breast cancer patients correlate with worse prognosis. Consistently, overexpression of ZMYND11 suppresses cancer cell growth in vitro and tumour formation in mice. Together, this study identifies ZMYND11 as an H3.3-specific reader of H3K36me3 that links the histone-variant-mediated transcription elongation control to tumour suppression.

doi: 10.1038/nature13045

Direct measurement of local oxygen concentration in the bone marrow of live animals p.269

Characterization of how the microenvironment, or niche, regulates stem cell activity is central to understanding stem cell biology and to developing strategies for the therapeutic manipulation of stem cells. Low oxygen tension (hypoxia) is commonly thought to be a shared niche characteristic in maintaining quiescence in multiple stem cell types. However, support for the existence of a hypoxic niche has largely come from indirect evidence such as proteomic analysis, expression of hypoxia inducible factor-1α (Hif-1α) and related genes, and staining with surrogate hypoxic markers (for example, pimonidazole). Here we perform direct in vivo measurements of local oxygen tension (p_O2) in the bone marrow of live mice. Using two-photon phosphorescence lifetime microscopy, we determined the absolute p_O2 of the bone marrow to be quite low (<32 mm Hg) despite very high vascular density. We further uncovered heterogeneities in local p_O2, with the lowest p_O2 (∼9.9 mm Hg, or 1.3%) found in deeper peri-sinusoidal regions. The endosteal region, by contrast, is less hypoxic as it is perfused with small arteries that are often positive for the marker nestin. These p_O2 values change markedly after radiation and chemotherapy, pointing to the role of stress in altering the stem cell metabolic microenvironment.

doi: 10.1038/nature13034