네이처 컨텐츠

Editorials

Be here now p.399

Growth in yields of the cereal must double if the Green Revolution is to be put back on track.

doi: 10.1038/507399a

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Wheat lag p.399

New views of quantum theory that can be tested and have practical applications bring welcome echoes of physics past.

doi: 10.1038/507399b

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A parlous state p.400

The decay at ancient Pompeii is symbolic of a deeper malaise in Italy’s heritage.

doi: 10.1038/507400a

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News

News Features

A tolerant approach p.418

Despite a long record of failure, a few immunologists continue to pursue precisely targeted therapies for autoimmune diseases.

Ken Garber

doi: 10.1038/507418a

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News & Views

Updating views of visual updating p.434

Our brains create a stable view of the world even though our eyes dart around. A study of how the brain might compensate for eye movements reveals an unexpected twist in the vision-stabilizing mechanism. See Letter p.504

John A. Assad

doi: 10.1038/507434a

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Stranded in no-man's-land p.435

The discovery of a second resident in a region of the Solar System called the inner Oort cloud prompts fresh thinking about this no-man's-land between the giant planets and the reservoir of comets of long orbital period. See Letter p.471

Megan E. Schwamb

doi: 10.1038/507435a

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Methane minimalism p.436

A meta-analysis of methane emissions at the ecosystem level reveals a simple exponential dependence on temperature, despite the complex array of factors that control this process.

Tori M. Hoehler & Marc J. Alperin

doi: 10.1038/nature13215

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A high bar for decadal forecasts of El Niño p.437

Climate simulations suggest that multi-decadal periods of high and low variability in the phenomenon known as the El Niño-Southern Oscillation in the tropical Pacific Ocean may be entirely unpredictable.

Pedro DiNezio

doi: 10.1038/507437a

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A protective factor for the ageing brain p.439

What guards the aged brain against neurodegeneration? A study finds that the REST protein has a central role in protecting ageing neurons from death and in maintaining cognitive capacity in the elderly.

Li-Huei Tsai & Ram Madabhushi

doi: 10.1038/nature13214

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Chaos in the cold p.440

A marriage between theory and experiment has shown that ultracold erbium atoms trapped with laser light and subjected to a magnetic field undergo collisions that are characterized by quantum chaos.

Paul S. Julienne

doi: 10.1038/nature13211

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The zinc link p.441

Increased influx of zinc into chondrocytes — the cells that make up cartilage — has been found to activate matrix-degrading enzymes that cause the destruction of cartilage in osteoarthritis.

Virginia Byers Kraus

doi: 10.1038/507441a

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Perspective

The ultimate physical limits of privacy p.443

Among those who make a living from the science of secrecy, worry and paranoia are just signs of professionalism. Can we protect our secrets against those who wield superior technological powers? Can we trust those who provide us with tools for protection? Can we even trust ourselves, our own freedom of choice? Recent developments in quantum cryptography show that some of these questions can be addressed and discussed in precise and operational terms, suggesting that privacy is indeed possible under surprisingly weak assumptions.

Artur Ekert & Renato Renner

doi: 10.1038/nature13132

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Articles

REST and stress resistance in ageing and Alzheimer’s disease p.448

REST, a developmental regulator, is markedly induced in human neurons during ageing but is lost in Alzheimer’s disease; REST represses genes that promote neurodegeneration, is neuroprotective in animal models, and is associated with cognitive preservation and longevity in humans.

Tao Lu, Liviu Aron, Joseph Zullo, Ying Pan, Haeyoung Kim, Yiwen Chen, Tun-Hsiang Yang, Hyun-Min Kim, Derek Drake, X. Shirley Liu + et al.

doi: 10.1038/nature13163

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An atlas of active enhancers across human cell types and tissues p.455

Using the FANTOM5 CAGE expression atlas, the authors show that bidirectional capped RNAs are a signature feature of active enhancers and identify over 40,000 enhancer candidates from over 800 human cell and tissue samples across the whole human body.

Robin Andersson, Claudia Gebhard, Irene Miguel-Escalada, Ilka Hoof, Jette Bornholdt, Mette Boyd, Yun Chen, Xiaobei Zhao, Christian Schmidl, Takahiro Suzuki + et al.

doi: 10.1038/nature12787

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A promoter-level mammalian expression atlas p.462

A study from the FANTOM consortium using single-molecule cDNA sequencing of transcription start sites and their usage in human and mouse primary cells, cell lines and tissues reveals insights into the specificity and diversity of transcription patterns across different mammalian cell types.

doi: 10.1038/nature13182

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Letters

A Sedna-like body with a perihelion of 80 astronomical units p.471

The observable Solar System can be divided into three distinct regions: the rocky terrestrial planets including the asteroids at 0.39 to 4.2 astronomical units (au) from the Sun (where 1 au is the mean distance between Earth and the Sun), the gas giant planets at 5 to 30 au from the Sun, and the icy Kuiper belt objects at 30 to 50 au from the Sun. The 1,000-kilometre-diameter dwarf planet Sedna was discovered ten years ago and was unique in that its closest approach to the Sun (perihelion) is 76 au, far greater than that of any other Solar System body. Formation models indicate that Sedna could be a link between the Kuiper belt objects and the hypothesized outer Oort cloud at around 10,000 au from the Sun. Here we report the presence of a second Sedna-like object, 2012 VP113, whose perihelion is 80 au. The detection of 2012 VP113 confirms that Sedna is not an isolated object; instead, both bodies may be members of the inner Oort cloud, whose objects could outnumber all other dynamically stable populations in the Solar System.

Chadwick A. Trujillo & Scott S. Sheppard

doi: 10.1038/nature13156

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Quantum chaos in ultracold collisions of gas-phase erbium atoms p.475

Atomic and molecular samples reduced to temperatures below one microkelvin, yet still in the gas phase, afford unprecedented energy resolution in probing and manipulating the interactions between their constituent particles. As a result of this resolution, atoms can be made to scatter resonantly on demand, through the precise control of a magnetic field. For simple atoms, such as alkalis, scattering resonances are extremely well characterized. However, ultracold physics is now poised to enter a new regime, where much more complex species can be cooled and studied, including magnetic lanthanide atoms and even molecules. For molecules, it has been speculated that a dense set of resonances in ultracold collision cross-sections will probably exhibit essentially random fluctuations, much as the observed energy spectra of nuclear scattering do. According to the Bohigas–Giannoni–Schmit conjecture, such fluctuations would imply chaotic dynamics of the underlying classical motion driving the collision. This would necessitate new ways of looking at the fundamental interactions in ultracold atomic and molecular systems, as well as perhaps new chaos-driven states of ultracold matter. Here we describe the experimental demonstration that random spectra are indeed found at ultralow temperatures. In the experiment, an ultracold gas of erbium atoms is shown to exhibit many Fano–Feshbach resonances, of the order of three per gauss for bosons. Analysis of their statistics verifies that their distribution of nearest-neighbour spacings is what one would expect from random matrix theory. The density and statistics of these resonances are explained by fully quantum mechanical scattering calculations that locate their origin in the anisotropy of the atoms’ potential energy surface. Our results therefore reveal chaotic behaviour in the native interaction between ultracold atoms.

Albert Frisch, Michael Mark, Kiyotaka Aikawa, Francesca Ferlaino, John L. Bohn, Constantinos Makrides, Alexander Petrov & Svetlana Kotochigova

doi: 10.1038/nature13137

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Reconciliation of the carbon budget in the ocean’s twilight zone p.480

Photosynthesis in the surface ocean produces approximately 100 gigatonnes of organic carbon per year, of which 5 to 15 per cent is exported to the deep ocean. The rate at which the sinking carbon is converted into carbon dioxide by heterotrophic organisms at depth is important in controlling oceanic carbon storage. It remains uncertain, however, to what extent surface ocean carbon supply meets the demand of water-column biota; the discrepancy between known carbon sources and sinks is as much as two orders of magnitude. Here we present field measurements, respiration rate estimates and a steady-state model that allow us to balance carbon sources and sinks to within observational uncertainties at the Porcupine Abyssal Plain site in the eastern North Atlantic Ocean. We find that prokaryotes are responsible for 70 to 92 per cent of the estimated remineralization in the twilight zone (depths of 50 to 1,000 metres) despite the fact that much of the organic carbon is exported in the form of large, fast-sinking particles accessible to larger zooplankton. We suggest that this occurs because zooplankton fragment and ingest half of the fast-sinking particles, of which more than 30 per cent may be released as suspended and slowly sinking matter, stimulating the deep-ocean microbial loop. The synergy between microbes and zooplankton in the twilight zone is important to our understanding of the processes controlling the oceanic carbon sink.

Sarah L. C. Giering, Richard Sanders, Richard S. Lampitt, Thomas R. Anderson, Christian Tamburini, Mehdi Boutrif, Mikhail V. Zubkov, Chris M. Marsay, Stephanie A. Henson, Kevin Saw + et al.

doi: 10.1038/nature13123

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Geomagnetic fluctuations reveal stable stratification at the top of the Earth’s core p.484

Modern observations of the geomagnetic field reveal fluctuations with a dominant period of about 60 years. These fluctuations are probably a result of waves in the liquid core, although the precise nature of the waves is uncertain. Common suggestions include a type of magnetic wave, known as a torsional oscillation, but recent studies favour periods that are too short to account for a 60-year fluctuation. Another possibility involves MAC waves, which arise from the interplay between magnetic, Archimedes and Coriolis forces. Waves with a suitable period can emerge when the top of the core is stably stratified. Here I show that MAC waves provide a good description of time-dependent zonal flow at the top of the core, as inferred from geomagnetic secular variation. The same wave motion can also account for unexplained fluctuations in the dipole field. Both of these independent predictions require a 140-kilometre-thick stratified layer with a buoyancy frequency comparable to the Earth’s rotation rate. Such a stratified layer could have a thermal origin, implying a core heat flow of about 13 terawatts. Alternatively, the layer could result from chemical stratification. In either case, the existence of a stratified layer at the top of the core obscures the nature of flow deeper in the core, where the magnetic field is continually regenerated.

Bruce Buffett

doi: 10.1038/nature13122

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Methane fluxes show consistent temperature dependence across microbial to ecosystem scales p.488

Methane (CH4) is an important greenhouse gas because it has 25 times the global warming potential of carbon dioxide (CO2) by mass over a century. Recent calculations suggest that atmospheric CH4 emissions have been responsible for approximately 20% of Earth’s warming since pre-industrial times. Understanding how CH4 emissions from ecosystems will respond to expected increases in global temperature is therefore fundamental to predicting whether the carbon cycle will mitigate or accelerate climate change. Methanogenesis is the terminal step in the remineralization of organic matter and is carried out by strictly anaerobic Archaea. Like most other forms of metabolism, methanogenesis is temperature-dependent. However, it is not yet known how this physiological response combines with other biotic processes (for example, methanotrophy, substrate supply, microbial community composition) and abiotic processes (for example, water-table depth) to determine the temperature dependence of ecosystem-level CH4 emissions. It is also not known whether CH4 emissions at the ecosystem level have a fundamentally different temperature dependence than other key fluxes in the carbon cycle, such as photosynthesis and respiration. Here we use meta-analyses to show that seasonal variations in CH4 emissions from a wide range of ecosystems exhibit an average temperature dependence similar to that of CH4 production derived from pure cultures of methanogens and anaerobic microbial communities. This average temperature dependence (0.96 electron volts (eV)), which corresponds to a 57-fold increase between 0 and 30°C, is considerably higher than previously observed for respiration (approximately 0.65 eV) and photosynthesis (approximately 0.3 eV). As a result, we show that both the emission of CH4 and the ratio of CH4 to CO2 emissions increase markedly with seasonal increases in temperature. Our findings suggest that global warming may have a large impact on the relative contributions of CO2 and CH4 to total greenhouse gas emissions from aquatic ecosystems, terrestrial wetlands and rice paddies.

Gabriel Yvon-Durocher, Andrew P. Allen, David Bastviken, Ralf Conrad, Cristian Gudasz, Annick St-Pierre, Nguyen Thanh-Duc & Paul A. del Giorgio

doi: 10.1038/nature13164

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Geographical limits to species-range shifts are suggested by climate velocity p.492

The reorganization of patterns of species diversity driven by anthropogenic climate change, and the consequences for humans, are not yet fully understood or appreciated. Nevertheless, changes in climate conditions are useful for predicting shifts in species distributions at global and local scales. Here we use the velocity of climate change to derive spatial trajectories for climatic niches from 1960 to 2009 (ref. 7) and from 2006 to 2100, and use the properties of these trajectories to infer changes in species distributions. Coastlines act as barriers and locally cooler areas act as attractors for trajectories, creating source and sink areas for local climatic conditions. Climate source areas indicate where locally novel conditions are not connected to areas where similar climates previously occurred, and are thereby inaccessible to climate migrants tracking isotherms: 16% of global surface area for 1960 to 2009, and 34% of ocean for the ‘business as usual’ climate scenario (representative concentration pathway (RCP) 8.5) representing continued use of fossil fuels without mitigation. Climate sink areas are where climate conditions locally disappear, potentially blocking the movement of climate migrants. Sink areas comprise 1.0% of ocean area and 3.6% of land and are prevalent on coasts and high ground. Using this approach to infer shifts in species distributions gives global and regional maps of the expected direction and rate of shifts of climate migrants, and suggests areas of potential loss of species richness.

Michael T. Burrows, David S. Schoeman, Anthony J. Richardson, Jorge García Molinos, Ary Hoffmann, Lauren B. Buckley, Pippa J. Moore, Christopher J. Brown, John F. Bruno, Carlos M. Duarte + et al.

doi: 10.1038/nature12976

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A suspension-feeding anomalocarid from the Early Cambrian p.496

Large, actively swimming suspension feeders evolved several times in Earth’s history, arising independently from groups as diverse as sharks, rays and stem teleost fishes, and in mysticete whales. However, animals occupying this niche have not been identified from the early Palaeozoic era. Anomalocarids, a group of stem arthropods that were the largest nektonic animals of the Cambrian and Ordovician periods, are generally thought to have been apex predators. Here we describe new material from Tamisiocaris borealis, an anomalocarid from the Early Cambrian (Series 2) Sirius Passet Fauna of North Greenland, and propose that its frontal appendage is specialized for suspension feeding. The appendage bears long, slender and equally spaced ventral spines furnished with dense rows of long and fine auxiliary spines. This suggests that T. borealis was a microphagous suspension feeder, using its appendages for sweep-net capture of food items down to 0.5 mm, within the size range of mesozooplankton such as copepods. Our observations demonstrate that large, nektonic suspension feeders first evolved during the Cambrian explosion, as part of an adaptive radiation of anomalocarids. The presence of nektonic suspension feeders in the Early Cambrian, together with evidence for a diverse pelagic community containing phytoplankton and mesozooplankton, indicate the existence of a complex pelagic ecosystem supported by high primary productivity and nutrient flux. Cambrian pelagic ecosystems seem to have been more modern than previously believed.

Jakob Vinther, Martin Stein, Nicholas R. Longrich & David A. T. Harper

doi: 10.1038/nature13010

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A primitive placoderm sheds light on the origin of the jawed vertebrate face p.500

Extant vertebrates form two clades, the jawless Cyclostomata (lampreys and hagfishes) and the jawed Gnathostomata (all other vertebrates), with contrasting facial architectures. These arise during development from just a few key differences in the growth patterns of the cranial primordia: notably, the nasal sacs and hypophysis originate from a single placode in cyclostomes but from separate placodes in gnathostomes, and infraoptic ectomesenchyme migrates forward either side of the single placode in cyclostomes but between the placodes in gnathostomes. Fossil stem gnathostomes preserve cranial anatomies rich in landmarks that provide proxies for developmental processes and allow the transition from jawless to jawed vertebrates to be broken down into evolutionary steps. Here we use propagation phase contrast synchrotron microtomography to image the cranial anatomy of the primitive placoderm (jawed stem gnathostome) Romundina, and show that it combines jawed vertebrate architecture with cranial and cerebral proportions resembling those of cyclostomes and the galeaspid (jawless stem gnathostome) Shuyu. This combination seems to be primitive for jawed vertebrates, and suggests a decoupling between ectomesenchymal growth trajectory, ectomesenchymal proliferation, and cerebral shape change during the origin of gnathostomes.

Vincent Dupret, Sophie Sanchez, Daniel Goujet, Paul Tafforeau & Per E. Ahlberg

doi: 10.1038/nature12980

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Visual space is compressed in prefrontal cortex before eye movements p.504

We experience the visual world through a series of saccadic eye movements, each one shifting our gaze to bring objects of interest to the fovea for further processing. Although such movements lead to frequent and substantial displacements of the retinal image, these displacements go unnoticed. It is widely assumed that a primary mechanism underlying this apparent stability is an anticipatory shifting of visual receptive fields (RFs) from their presaccadic to their postsaccadic locations before movement onset. Evidence of this predictive ‘remapping’ of RFs has been particularly apparent within brain structures involved in gaze control. However, critically absent among that evidence are detailed measurements of visual RFs before movement onset. Here we show that during saccade preparation, rather than remap, RFs of neurons in a prefrontal gaze control area massively converge towards the saccadic target. We mapped the visual RFs of prefrontal neurons during stable fixation and immediately before the onset of eye movements, using multi-electrode recordings in monkeys. Following movements from an initial fixation point to a target, RFs remained stationary in retinocentric space. However, in the period immediately before movement onset, RFs shifted by as much as 18 degrees of visual angle, and converged towards the target location. This convergence resulted in a threefold increase in the proportion of RFs responding to stimuli near the target region. In addition, like in human observers, the population of prefrontal neurons grossly mislocalized presaccadic stimuli as being closer to the target. Our results show that RF shifts do not predict the retinal displacements due to saccades, but instead reflect the overriding perception of target space during eye movements.

Marc Zirnsak, Nicholas A. Steinmetz, Behrad Noudoost, Kitty Z. Xu & Tirin Moore

doi: 10.1038/nature13149

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The E3 ligase Cbl-b and TAM receptors regulate cancer metastasis via natural killer cells p.508

Tumour metastasis is the primary cause of mortality in cancer patients and remains the key challenge for cancer therapy. New therapeutic approaches to block inhibitory pathways of the immune system have renewed hopes for the utility of such therapies. Here we show that genetic deletion of the E3 ubiquitin ligase Cbl-b (casitas B-lineage lymphoma-b) or targeted inactivation of its E3 ligase activity licenses natural killer (NK) cells to spontaneously reject metastatic tumours. The TAM tyrosine kinase receptors Tyro3, Axl and Mer (also known as Mertk) were identified as ubiquitylation substrates for Cbl-b. Treatment of wild-type NK cells with a newly developed small molecule TAM kinase inhibitor conferred therapeutic potential, efficiently enhancing anti-metastatic NK cell activity in vivo. Oral or intraperitoneal administration using this TAM inhibitor markedly reduced murine mammary cancer and melanoma metastases dependent on NK cells. We further report that the anticoagulant warfarin exerts anti-metastatic activity in mice via Cbl-b/TAM receptors in NK cells, providing a molecular explanation for a 50-year-old puzzle in cancer biology. This novel TAM/Cbl-b inhibitory pathway shows that it might be possible to develop a ‘pill’ that awakens the innate immune system to kill cancer metastases.

Magdalena Paolino, Axel Choidas, Stephanie Wallner, Blanka Pranjic, Iris Uribesalgo, Stefanie Loeser, Amanda M. Jamieson, Wallace Y. Langdon, Fumiyo Ikeda, Juan Pablo Fededa + et al.

doi: 10.1038/nature12998

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Transcription factor achaete-scute homologue 2 initiates follicular T-helper-cell development p.513

In immune responses, activated T cells migrate to B-cell follicles and develop into follicular T-helper (TFH) cells, a recently identified subset of CD4+ T cells specialized in providing help to B lymphocytes in the induction of germinal centres. Although Bcl6 has been shown to be essential in TFH-cell function, it may not regulate the initial migration of T cells or the induction of the TFH program, as exemplified by C-X-C chemokine receptor type 5 (CXCR5) upregulation. Here we show that expression of achaete-scute homologue 2 (Ascl2)—a basic helix–loop–helix (bHLH) transcription factor—is selectively upregulated in TFH cells. Ectopic expression of Ascl2 upregulates CXCR5 but not Bcl6, and downregulates C-C chemokine receptor 7 (CCR7) expression in T cells in vitro, as well as accelerating T-cell migration to the follicles and TFH-cell development in vivo in mice. Genome-wide analysis indicates that Ascl2 directly regulates TFH-related genes whereas it inhibits expression of T-helper cell 1 (TH1) and TH17 signature genes. Acute deletion of Ascl2, as well as blockade of its function with the Id3 protein in CD4+ T cells, results in impaired TFH-cell development and germinal centre response. Conversely, mutation of Id3, known to cause antibody-mediated autoimmunity, greatly enhances TFH-cell generation. Thus, Ascl2 directly initiates TFH-cell development.

Xindong Liu, Xin Chen, Bo Zhong, Aibo Wang, Xiaohu Wang, Fuliang Chu, Roza I. Nurieva, Xiaowei Yan, Ping Chen, Laurens G. van der Flier + et al.

doi: 10.1038/nature12910

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Structure-based programming of lymph-node targeting in molecular vaccines p.519

In cancer patients, visual identification of sentinel lymph nodes (LNs) is achieved by the injection of dyes that bind avidly to endogenous albumin, targeting these compounds to LNs, where they are efficiently filtered by resident phagocytes. Here we translate this ‘albumin hitchhiking’ approach to molecular vaccines, through the synthesis of amphiphiles (amph-vaccines) comprising an antigen or adjuvant cargo linked to a lipophilic albumin-binding tail by a solubility-promoting polar polymer chain. Administration of structurally optimized CpG-DNA/peptide amph-vaccines in mice resulted in marked increases in LN accumulation and decreased systemic dissemination relative to their parent compounds, leading to 30-fold increases in T-cell priming and enhanced anti-tumour efficacy while greatly reducing systemic toxicity. Amph-vaccines provide a simple, broadly applicable strategy to simultaneously increase the potency and safety of subunit vaccines.

Haipeng Liu, Kelly D. Moynihan, Yiran Zheng, Gregory L. Szeto, Adrienne V. Li, Bonnie Huang, Debra S. Van Egeren, Clara Park & Darrell J. Irvine

doi: 10.1038/nature12978

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