© Mario Izquierdo

 Resumen de noticias: Nature

Nature - Issue - nature.com science feeds

Editorial

· Keep doors open for constructive dialogue between religion and science. (15.05.2017) A meeting between the Pope, patients and researchers acknowledges how the two sectors can help each other. 265-265.

· The United States must act quickly to control the use of e-cigarettes. (15.05.2017) The nation needs to end the long-running battle between regulators, lawmakers and industry. 265-266.

· Why US nuclear sites are a ticking time bomb. (17.05.2017) The Department of Energy needs to prioritize the clean-up of nuclear waste. 266-266.

Column

· Rescue old data before it?s too late. (16.05.2017) If we don’t act soon to preserve past records, invaluable knowledge will be lost, warns Elizabeth Griffin. 267-267.

Seven Days

· Ebola outbreak in the Congo, tuberculosis drug resistance in Russia and GM mustard seeds in India. (17.05.2017) The week in science: 12–18 May 2017. 270-271.

News

· How Trump?s science cuts could hurt states that voted for him. (17.05.2017) Rural and struggling areas have benefited from funding that is now at risk. 273-274.

· China cracks down on fake data in drug trials. (11.05.2017) Researchers and manufacturers face possible jail time— or execution — for fraudulent submissions to nation's drug agency. 275-275.

· Ancient-genome study finds Bronze Age?Beaker culture? invaded Britain. (17.05.2017) Famous bell-shaped pots associated with group of immigrants who may have displaced Neolithic farmers. 276-277.

· Geneticists enlist engineered virus and CRISPR to battle citrus disease. (16.05.2017) Desperate farmers hope scientists can beat pathogen that is wrecking the US orange harvest. 277-278.

· Century-old tumours offer rare cancer clues. (10.05.2017) DNA sequences from 100-year-old tumour samples could bolster childhood cancer research. 278-278.

Feature

· The wooden skyscrapers that could help to cool the planet. (17.05.2017) Large timber buildings are getting safer, stronger and taller. They may also offer a way to slow down global warming. 280-282.

Comment

· Biology needs more staff scientists. (16.05.2017) Independent professionals advance science in ways faculty-run labs cannot, and such positions keep talented people in research, argues Steven Hyman. 283-284.

Books and Arts

· Space Science: First three round the Moon. (17.05.2017) Roger Launius on a valentine to the astronauts behind Apollo 8 and Earthrise. 285-286.

· Inequality: Live poor, die young. (17.05.2017) Abigail A. Sewell examines a physician's study of how deprivation shortens lifespan. 286-287.

· Environment: Law for a healthy planet. (17.05.2017) Hari Osofsky draws lessons from the story of a pioneering environmental lawyer and his firm. 288-288.

Correspondence

· China: Rail network must protect giant pandas. (17.05.2017) Construction of a high-speed rail network in southwest China is a welcome boost to the region's economy. As the network expands under the country's 13th Five-Year Plan (2016–20), we urge the government to reinforce and extend its efforts to protect the region's giant pandas and 289-289.

· Global health: Boost multinational clinical research. (17.05.2017) Global cooperation in clinical research maximizes access to patients, enables resource sharing and increases the applicability of research findings. Yet academic trials are rarely multinational because they are beset with funding problems and variations in legal, regulatory and ethical requirements. The Clinical Research Initiative for 289-289.

· Seismology: Japan must admit it can't predict quakes. (17.05.2017) Japan's government is still failing to protect the public against earthquakes, six years on from the devastating magnitude-9.1 Tohoku earthquake of 2011. In my view, it urgently needs to abandon flawed, old policies and focus instead on implementing effective countermeasures that are based on sound 289-289.

· Multidisciplinarity: Widen discipline span of Nature papers. (17.05.2017) Our informal analysis indicates that the biological sciences have dominated Nature's research content for more than 50 years. In an age that calls for greater multidisciplinarity, we suggest that the journal should include a broader range of high-impact papers from fields such as mathematics, 289-289.

Obituary

· Hans Dehmelt (1922?2017). (17.05.2017) Nobel prizewinner who trapped electrons and demonstrated quantum jumps. 290-290.

Naturejobs

· Work?life balance: Break or burn out. (17.05.2017) Taking time off from work is crucial for avoiding stress and depression, and their potential consequences. 375-377.

· A mentor?s acid test. (17.05.2017) Mutual respect, guidance and support are key to a fruitful relationship with trainees, says W. Larry Kenney. 377-377.

Futures

· Life, hacked. (17.05.2017) Out for a duck. 380-380.

Outlook

· University spin-offs. (17.05.2017) S1-S1.

· Therapeutic developments: Masters of medicine. (17.05.2017) Drawing on the latest research, companies are developing more-effective therapies. S4-S9.

· Software: Picture perfect. (17.05.2017) Improvements in image capture and viewing experience. S12-S12.

· Energy: Powering change. (17.05.2017) Innovators are finding better ways to produce, store and use energy, on Earth and beyond. S13-S14.

· Materials and engineering: Rebuilding the world. (17.05.2017) Scientists commercializing technologies that enable sturdier and more-sustainable structures. S15-S20.

Correction

· Correction. (17.05.2017) The Correspondence by Tim Birkhead and Robert Montgomerie (Nature545, 30;10.1038/545030a2017) wrongly stated that PeerJ is a not-for-profit journal. In fact, it is a for-profit company. 289-289.

News& Views

· Cancer: Tumours build their niche. (10.05.2017) It emerges that tumour cells can give rise to non-dividing cells that form part of the supporting microenvironment known as the niche. These niche cells secrete proteins that drive tumour growth and progression. See Letters p.355& p.360 292-293.

· Atomic physics: Quantum theory verified by experiment. (17.05.2017) Systems of quantum objects can be characterized by the correlations between the objects. A technique that precisely measures even the most delicate of these correlations allows models of quantum systems to be tested. See Letter p.323 293-294.

· Ageing: Tools to eliminate senescent cells. (10.05.2017) Ageing and many diseases are partly driven by the accumulation of damaged cells that no longer divide. It emerges that these senescent cells can be eradicated in mice using a drug that interferes with the activity of the protein FOXO4. 294-296.

· 50& 100 Years Ago. (17.05.2017) 50 Years AgoMr Anthony Wedgwood Benn, Minister of Technology, seems hopeful that Britain’s application to join the Common Market may help to limit the flow of qualified manpower to the United States. Speaking at a symposium … on “Aspects of the Brain Drain”, he 295-295.

· In Retrospect: Half a century of robust climate models. (17.05.2017) A classic paper in 1967 reported key advances in climate modelling that enabled a convincing quantification of the global-warming effects of carbon dioxide— laying foundations for the models that underpin climate research today. 296-297.

· Behavioural economics: Occasional errors can benefit coordination. (17.05.2017) The chances of solving a problem that involves coordination between people are increased by introducing robotic players that sometimes make mistakes. This finding has implications for real-world coordination problems. See Letter p.370 297-298.

Article

· Predictive compound accumulation rules yield a broad-spectrum antibiotic. (10.05.2017) Most small molecules are unable to rapidly traverse the outer membrane of Gram-negative bacteria and accumulate inside these cells, making the discovery of much-needed drugs against these pathogens challenging. Current understanding of the physicochemical properties that dictate small-molecule accumulation in Gram-negative bacteria is largely based 299-304.

· Endothelial TLR4 and the microbiome drive cerebral cavernous malformations. (10.05.2017) Cerebral cavernous malformations (CCMs) are a cause of stroke and seizure for which no effective medical therapies yet exist. CCMs arise from the loss of an adaptor complex that negatively regulates MEKK3–KLF2/4 signalling in brain endothelial cells, but upstream activators of this disease pathway have 305-310.

· Discovery of nitrate?CPK?NLP signalling in central nutrient?growth networks. (10.05.2017) Nutrient signalling integrates and coordinates gene expression, metabolism and growth. However, its primary molecular mechanisms remain incompletely understood in plants and animals. Here we report unique Ca2+ signalling triggered by nitrate with live imaging of an ultrasensitive biosensor in Arabidopsis leaves and 311-316.

· Selectivity determinants of GPCR?G-protein binding. (10.05.2017) The selective coupling of G-protein-coupled receptors (GPCRs) to specific G proteins is critical to trigger the appropriate physiological response. However, the determinants of selective binding have remained elusive. Here we reveal the existence of a selectivity barcode (that is, patterns of amino acids) on each 317-322.

Letter

· Experimental characterization of a quantum many-body system via higher-order correlations. (17.05.2017) Quantum systems can be characterized by their correlations. Higher-order (larger than second order) correlations, and the ways in which they can be decomposed into correlations of lower order, provide important information about the system, its structure, its interactions and its complexity. The measurement of such correlation functions is therefore an essential tool for reading, verifying and characterizing quantum simulations. Although higher-order correlation functions are frequently used in theoretical calculations, so far mainly correlations up to second order have been studied experimentally. Here we study a pair of tunnel-coupled one-dimensional atomic superfluids and characterize the corresponding quantum many-body problem by measuring correlation functions. We extract phase correlation functions up to tenth order from interference patterns and analyse whether, and under what conditions, these functions factorize into correlations of lower order. This analysis characterizes the essential features of our system, the relevant quasiparticles, their interactions and topologically distinct vacua. From our data we conclude that in thermal equilibrium our system can be seen as a quantum simulator of the sine-Gordon model, relevant for diverse disciplines ranging from particle physics to condensed matter. The measurement and evaluation of higher-order correlation functions can easily be generalized to other systems and to study correlations of any other observable such as density, spin and magnetization. It therefore represents a general method for analysing quantum many-body systems from experimental data. 323-326.

· Topological defects control collective dynamics in neural progenitor cell cultures. (12.04.2017) Cultured stem cells have become a standard platform not only for regenerative medicine and developmental biology but also for biophysical studies. Yet, the characterization of cultured stem cells at the level of morphology and of the macroscopic patterns resulting from cell-to-cell interactions remains largely qualitative. Here we report on the collective dynamics of cultured murine neural progenitor cells (NPCs), which are multipotent stem cells that give rise to cells in the central nervous system. At low densities, NPCs moved randomly in an amoeba-like fashion. However, NPCs at high density elongated and aligned their shapes with one another, gliding at relatively high velocities. Although the direction of motion of individual cells reversed stochastically along the axes of alignment, the cells were capable of forming an aligned pattern up to length scales similar to that of the migratory stream observed in the adult brain. The two-dimensional order of alignment within the culture showed a liquid-crystalline pattern containing interspersed topological defects with winding numbers of +1/2 and−1/2 (half-integer due to the nematic feature that arises from the head–tail symmetry of cell-to-cell interaction). We identified rapid cell accumulation at +1/2 defects and the formation of three-dimensional mounds. Imaging at the single-cell level around the defects allowed us to quantify thevelocity field and the evolving cell density; cells not only concentrate at +1/2 defects, but also escape from −1/2 defects. We propose a generic mechanism for the instability in cell density around the defects that arises from the interplay between the anisotropic friction and the active force field. 327-331.

· Continental crust formation on early Earth controlled by intrusive magmatism. (08.05.2017) The global geodynamic regime of early Earth, which operated before the onset of plate tectonics, remains contentious. As geological and geochemical data suggest hotter Archean mantle temperature and more intense juvenile magmatism than in the present-day Earth, two crust–mantle interaction modes differing in melt eruption efficiency have been proposed: the Io-like heat-pipe tectonics regime dominated by volcanism and the “Plutonic squishy lid” tectonics regime governed by intrusive magmatism, which is thought to apply to the dynamics of Venus. Both tectonicsregimes are capable of producing primordial tonalite–trondhjemite–granodiorite (TTG) continental crust but lithospheric geotherms and crust production rates as well as proportions of various TTG compositions differ greatly, which implies that the heat-pipe and Plutonic squishy lid hypotheses can be tested using natural data. Here we investigate the creation of primordial TTG-like continental crust using self-consistent numerical models of global thermochemical convection associated with magmatic processes. We show that the volcanism-dominated heat-pipe tectonics model results in cold crustal geotherms and is not able to produce Earth-like primordial continental crust. In contrast, the Plutonic squishy lid tectonics regime dominated by intrusive magmatism results in hotter crustal geotherms and is capable of reproducing the observed proportions of various TTG rocks. Using a systematic parameter study, we show that the typical modern eruption efficiency of less than 40 per cent leads to the production of the expected amounts of the three main primordial crustal compositions previously reported from field data (low-, medium- and high-pressure TTG). Our study thus suggests that the pre-plate-tectonics Archean Earth operated globally in the Plutonic squishy lid regime rather than in an Io-like heat-pipe regime. 332-335.

· Experimental evidence that thrust earthquake ruptures might open faults. (01.05.2017) Many of Earth’s great earthquakes occur on thrust faults. These earthquakes predominantly occur within subduction zones, such as the 2011 moment magnitude 9.0 eathquake in Tohoku-Oki, Japan, or along large collision zones, such as the 1999 moment magnitude 7.7 earthquake in Chi-Chi, Taiwan. Notably, these twoearthquakes had a maximum slip that was very close to the surface. This contributed to the destructive tsunami that occurred during the Tohoku-Oki event and to the large amount of structural damage caused by the Chi-Chi event. The mechanism that results in such large slip near the surface is poorlyunderstood as shallow parts of thrust faults are considered to be frictionally stable. Here we use earthquake rupture experiments to reveal the existence of a torquing mechanism of thrust fault ruptures near the free surface that causes them to unclamp and slip large distances. Complementary numerical modelling of the experiments confirms that the hanging-wall wedge undergoes pronounced rotation in one direction as the earthquake rupture approaches the free surface, and this torque is released as soon as the rupture breaks the free surface, resulting in the unclamping and violent ‘flapping’ of the hanging-wall wedge. Our results imply that the shallow extent of the seismogenic zone of a subducting interface is not fixed and can extend up to the trench during great earthquakes through a torquing mechanism. 336-339.

· A rhodopsin in the brain functions in circadian photoentrainment in Drosophila. (10.05.2017) Animals partition their daily activity rhythms through their internal circadian clocks, which are synchronized by oscillating day–night cycles of light. The fruitfly Drosophila melanogaster senses day–night cycles in part through rhodopsin-dependent light reception in the compound eye and photoreceptor cells in the Hofbauer–Buchner eyelet. A more noteworthy light entrainment pathway is mediated by central pacemaker neurons in the brain. The Drosophila circadian clock is extremely sensitive to light. However, the only known light sensor in pacemaker neurons, the flavoprotein cryptochrome (Cry), responds only to high levels of light in vitro. These observations indicate that there is an additional light-sensing pathway in fly pacemaker neurons. Here we describe a previously uncharacterized rhodopsin, Rh7, which contributes to circadian light entrainment by circadian pacemaker neurons in the brain. The pacemaker neurons respond to violet light, and this response depends on Rh7. Loss of either cry or rh7 causedminor defects in photoentrainment, whereas loss of both caused profound impairment. The circadian photoresponse to constant light was impaired in rh7 mutant flies, especially under dim light. The demonstration that Rh7 functions in circadian pacemaker neurons represents, to our knowledge, the firstrole for an opsin in the central brain. 340-344.

· Whole-brain serial-section electron microscopy in larval zebrafish. (10.05.2017) High-resolution serial-section electron microscopy (ssEM) makes it possible to investigate the dense meshwork of axons, dendrites, and synapses that form neuronal circuits. However, the imaging scale required to comprehensively reconstruct these structures is more than ten orders of magnitude smaller than the spatial extents occupied by networks of interconnected neurons, some of which span nearly the entire brain. Difficulties in generating and handling data for large volumes at nanoscale resolution have thus restricted vertebrate studies to fragments of circuits. These efforts were recently transformed by advances in computing, sample handling, and imaging techniques, but high-resolution examination of entire brains remains a challenge. Here, we present ssEM data for the complete brain of a larval zebrafish (Danio rerio) at 5.5 days post-fertilization. Our approach utilizes multiple rounds of targeted imaging at different scales to reduce acquisition time and data management requirements. The resulting dataset can be analysed to reconstruct neuronal processes, permitting us to survey all myelinated axons (the projectome). These reconstructions enable precise investigations of neuronal morphology, which reveal remarkable bilateral symmetry in myelinated reticulospinal and lateral line afferent axons. We further set the stage for whole-brain structure–function comparisons by co-registering functional reference atlases and in vivo two-photon fluorescence microscopy data from the same specimen. All obtained images and reconstructions are provided as an open-access resource. 345-349.

· Floor-plate-derived netrin-1 is dispensable for commissural axon guidance. (26.04.2017) Netrin-1 is an evolutionarily conserved, secreted extracellular matrix protein involved in axon guidance at the central nervous system midline. Netrin-1 is expressed by cells localized at the central nervous system midline, such as those of the floor plate in vertebrate embryos. Growth cone turning assays and three-dimensional gel diffusion assays have shown that netrin-1 can attract commissural axons. Loss-of-function experiments further demonstrated that commissural axon extension to the midline is severely impaired in the absence of netrin-1 (refs 3, 7, 8, 9). Together, these data have long supported a model in which commissural axons are attracted by a netrin-1 gradient diffusing from the midline. Here we selectively ablate netrin-1 expression in floor-plate cells using a Ntn1 conditional knockout mouse line. We find that hindbrain and spinal cord commissural axons develop normally in the absence of floor-plate-derived netrin-1. Furthermore, we show that netrin-1 is highly expressed by cells in the ventricular zone, which can release netrin-1 at the pial surface where it binds to commissural axons. Notably, Ntn1 deletion from the ventricular zone phenocopies commissural axon guidance defects previously described in Ntn1-knockout mice. These results show that the classical view that attraction of commissural axons is mediated by a gradient of floor-plate-derived netrin-1 is inaccurate and that netrin-1 primarily acts locally by promoting growth cone adhesion. 350-354.

· A Wnt-producing niche drives proliferative potential and progression in lung adenocarcinoma. (10.05.2017) The heterogeneity of cellular states in cancer has been linked to drug resistance, cancer progression and the presence of cancer cells with properties of normal tissue stem cells. Secreted Wnt signals maintain stem cells in various epithelial tissues, including in lung development and regeneration. Here we show that mouse and human lung adenocarcinomas display hierarchical features with two distinct subpopulations, one with high Wnt signalling activity and another forming a niche that provides the Wnt ligand. The Wnt responder cells showed increased tumour propagation ability, suggesting that these cells have features of normal tissue stem cells. Genetic perturbation of Wnt production or signalling suppressed tumour progression. Small-molecule inhibitors targeting essential posttranslational modification of Wnt reduced tumour growth and markedly decreased the proliferative potential of lung cancer cells, leading to improved survival of tumour-bearing mice. These results indicate that strategies for disrupting pathways that maintain stem-like and niche cell phenotypes can translate into effective anti-cancer therapies. 355-359.

· Intratumoural heterogeneity generated by Notch signalling promotes small-cell lung cancer. (10.05.2017) The Notch signalling pathway mediates cell fate decisions and is tumour suppressive or oncogenic depending on the context. During lung development, Notch pathway activation inhibits the differentiation of precursor cells to a neuroendocrine fate. In small-cell lung cancer, an aggressive neuroendocrine lung cancer, loss-of-function mutations in NOTCH genes and the inhibitory effects of ectopic Notch activation indicate that Notch signalling is tumour suppressive. Here we show that Notch signalling can be both tumour suppressive and pro-tumorigenic in small-cell lung cancer. Endogenous activation of the Notch pathway results in a neuroendocrine to non-neuroendocrine fate switch in 10–50% of tumour cells in a mouse model of small-cell lung cancer and in human tumours. This switch is mediated in part by Rest (also known as Nrsf), a transcriptional repressor that inhibits neuroendocrine gene expression. Non-neuroendocrine Notch-active small-cell lung cancer cells are slow growing, consistent with a tumour-suppressive role for Notch, but these cells are also relatively chemoresistant and provide trophic support to neuroendocrine tumour cells, consistent with a pro-tumorigenic role. Importantly, Notch blockade in combination with chemotherapy suppresses tumour growth and delays relapse in pre-clinical models. Thus, small-cell lung cancer tumours generate their own microenvironment via activation of Notch signalling in a subset of tumour cells, and the presence of these cells may serve as a biomarker for the use of Notch pathway inhibitors in combination with chemotherapy in select patients with small-cell lung cancer. 360-364.

· TRAF2 and OTUD7B govern a ubiquitin-dependent switch that regulates mTORC2 signalling. (10.05.2017) The mechanistic target of rapamycin (mTOR) has a key role in the integration of various physiological stimuli to regulate several cell growth and metabolic pathways. mTOR primarily functions as a catalytic subunit in two structurally related but functionally distinct multi-component kinase complexes, mTOR complex 1 (mTORC1) and mTORC2 (refs 1, 2). Dysregulation of mTOR signalling is associated with a variety of human diseases, including metabolic disorders and cancer. Thus, both mTORC1 and mTORC2 kinase activity is tightly controlled in cells. mTORC1 is activated by both nutrients and growth factors, whereas mTORC2 responds primarily to extracellular cues such as growth-factor-triggered activation of PI3K signalling. Although both mTOR and GβL (also known as MLST8) assemble into mTORC1 and mTORC2 (refs 11, 12, 13, 14, 15), it remains largely unclear what drives the dynamic assembly of these two functionally distinct complexes. Here we show, in humans and mice, that the K63-linked polyubiquitination status of GβL dictates the homeostasis of mTORC2 formation and activation. Mechanistically, the TRAF2 E3 ubiquitin ligase promotes K63-linked polyubiquitination of GβL, which disrupts its interaction with the unique mTORC2 component SIN1 (refs 12, 13, 14) to favour mTORC1 formation. By contrast, the OTUD7B deubiquitinase removes polyubiquitin chains from GβL to promote GβL interaction with SIN1, facilitating mTORC2 formation in response to various growth signals.Moreover, loss of critical ubiquitination residues in GβL, by either K305R/K313R mutations or a melanoma-associated GβL(ΔW297) truncation, leads to elevated mTORC2 formation, which facilitates tumorigenesis, in part by activating AKT oncogenic signalling. In support of a physiologically pivotal role for OTUD7B in the activation of mTORC2/AKT signalling, genetic deletion of Otud7b in mice suppresses Akt activation and Kras-driven lung tumorigenesis in vivo. Collectively, our study reveals a GβL-ubiquitination-dependent switch that fine-tunes the dynamic organization and activation of the mTORC2 kinase under both physiological and pathological conditions. 365-369.

· Locally noisy autonomous agents improve global human coordination in network experiments. (17.05.2017) Coordination in groups faces a sub-optimization problem and theory suggests that some randomness may help to achieve global optima. Here we performed experiments involving a networked colour coordination game in which groups of humans interacted with autonomous software agents (known as bots). Subjects (n = 4,000) were embedded in networks (n = 230) of 20 nodes, to which we sometimes added 3 bots. The bots were programmed with varying levels of behavioural randomness and different geodesic locations. We show that bots acting with small levels of random noise and placed in central locations meaningfully improve the collective performance of human groups, accelerating the median solution time by 55.6%. This is especially the case when the coordination problem is hard. Behavioural randomness worked not only by making the task of humans to whom the bots were connected easier, but also by affecting the gameplay of the humans among themselves and hence creating further cascades of benefit in global coordination in these heterogeneous systems. 370-374.

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