Nature (Nature)

Publications in this journal

• Article: Crystal structure of a nitrate/nitrite exchanger.

  Hongjin Zheng, Goragot Wisedchaisri, Tamir Gonen
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  ABSTRACT: Mineral nitrogen in nature is often found in the form of nitrate (NO3(-)). Numerous microorganisms evolved to assimilate nitrate and use it as a major source of mineral nitrogen uptake. Nitrate, which is central in nitrogen metabolism, is first reduced to nitrite (NO2(-)) through a two-electron reduction reaction. The accumulation of cellular nitrite can be harmful because nitrite can be reduced to the cytotoxic nitric oxide. Instead, nitrite is rapidly removed from the cell by channels and transporters, or reduced to ammonium or dinitrogen through the action of assimilatory enzymes. Despite decades of effort no structure is currently available for any nitrate transport protein and the mechanism by which nitrate is transported remains largely unknown. Here we report the structure of a bacterial nitrate/nitrite transport protein, NarK, from Escherichia coli, with and without substrate. The structures reveal a positively charged substrate-translocation pathway lacking protonatable residues, suggesting that NarK functions as a nitrate/nitrite exchanger and that protons are unlikely to be co-transported. Conserved arginine residues comprise the substrate-binding pocket, which is formed by association of helices from the two halves of NarK. Key residues that are important for substrate recognition and transport are identified and related to extensive mutagenesis and functional studies. We propose that NarK exchanges nitrate for nitrite by a rocker switch mechanism facilitated by inter-domain hydrogen bond networks.
  Nature 05/2013;
• Article: Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells.

  Cosimo Commisso, Shawn M Davidson, Rengin G Soydaner-Azeloglu, Seth J Parker, Jurre J Kamphorst, Sean Hackett, Elda Grabocka, Michel Nofal, Jeffrey A Drebin, Craig B Thompson, Joshua D Rabinowitz, Christian M Metallo, Matthew G Vander Heiden, Dafna Bar-Sagi
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  ABSTRACT: Macropinocytosis is a highly conserved endocytic process by which extracellular fluid and its contents are internalized into cells through large, heterogeneous vesicles known as macropinosomes. Oncogenic Ras proteins have been shown to stimulate macropinocytosis but the functional contribution of this uptake mechanism to the transformed phenotype remains unknown. Here we show that Ras-transformed cells use macropinocytosis to transport extracellular protein into the cell. The internalized protein undergoes proteolytic degradation, yielding amino acids including glutamine that can enter central carbon metabolism. Accordingly, the dependence of Ras-transformed cells on free extracellular glutamine for growth can be suppressed by the macropinocytic uptake of protein. Consistent with macropinocytosis representing an important route of nutrient uptake in tumours, its pharmacological inhibition compromises the growth of Ras-transformed pancreatic tumour xenografts. These results identify macropinocytosis as a mechanism by which cancer cells support their unique metabolic needs and point to the possible exploitation of this process in the design of anticancer therapies.
  Nature 05/2013;
• Article: De novo mutations in histone-modifying genes in congenital heart disease.

  Samir Zaidi, Murim Choi, Hiroko Wakimoto, Lijiang Ma, Jianming Jiang, John D Overton, Angela Romano-Adesman, Robert D Bjornson, Roger E Breitbart, Kerry K Brown, [......], Peter S White, Ismee A Williams, Hongyu Zhao, Jonathan G Seidman, Martina Brueckner, Wendy K Chung, Bruce D Gelb, Elizabeth Goldmuntz, Christine E Seidman, Richard P Lifton
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  ABSTRACT: Congenital heart disease (CHD) is the most frequent birth defect, affecting 0.8% of live births. Many cases occur sporadically and impair reproductive fitness, suggesting a role for de novo mutations. Here we compare the incidence of de novo mutations in 362 severe CHD cases and 264 controls by analysing exome sequencing of parent-offspring trios. CHD cases show a significant excess of protein-altering de novo mutations in genes expressed in the developing heart, with an odds ratio of 7.5 for damaging (premature termination, frameshift, splice site) mutations. Similar odds ratios are seen across the main classes of severe CHD. We find a marked excess of de novo mutations in genes involved in the production, removal or reading of histone 3 lysine 4 (H3K4) methylation, or ubiquitination of H2BK120, which is required for H3K4 methylation. There are also two de novo mutations in SMAD2, which regulates H3K27 methylation in the embryonic left-right organizer. The combination of both activating (H3K4 methylation) and inactivating (H3K27 methylation) chromatin marks characterizes 'poised' promoters and enhancers, which regulate expression of key developmental genes. These findings implicate de novo point mutations in several hundreds of genes that collectively contribute to approximately 10% of severe CHD.
  Nature 05/2013;
• Article: Symmetry study deemed a fraud.

  Eugenie Samuel Reich
  Nature 05/2013; 497(7448):170-1.
• Article: History: Non-coding RNA foreseen 48 years ago.

  Henry Harris
  Nature 05/2013; 497(7448):188.
• Article: Neuroprosthetics: Once more, with feeling.

  Roberta Kwok
  Nature 05/2013; 497(7448):176-8.
• Article: China's citizens must act to save their environment.

  Qiang Wang
  Nature 05/2013; 497(7448):159.
• Article: Global warming: A call for peace on climate and conflict.

  Andrew R Solow
  Nature 05/2013; 497(7448):179-80.
• Article: Climate mitigation: An open dialogue on solar engineering.

  John Shepherd, Berhanu Abegaz, Jane Long
  Nature 05/2013; 497(7448):188.
• Article: Nuclear physics: Exotic pear-shaped nuclei.

  C J Kim Lister, Jonathan Butterworth
  Nature 05/2013; 497(7448):190-1.
• Article: Sustainable mobility: A vision of our transport future.

  Lawrence D Burns
  Nature 05/2013; 497(7448):181-2.
• Article: Future sea-level rise from Greenland's main outlet glaciers in a warming climate.

  Faezeh M Nick, Andreas Vieli, Morten Langer Andersen, Ian Joughin, Antony Payne, Tamsin L Edwards, Frank Pattyn, Roderik S W van de Wal
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  ABSTRACT: Over the past decade, ice loss from the Greenland Ice Sheet increased as a result of both increased surface melting and ice discharge to the ocean. The latter is controlled by the acceleration of ice flow and subsequent thinning of fast-flowing marine-terminating outlet glaciers. Quantifying the future dynamic contribution of such glaciers to sea-level rise (SLR) remains a major challenge because outlet glacier dynamics are poorly understood. Here we present a glacier flow model that includes a fully dynamic treatment of marine termini. We use this model to simulate behaviour of four major marine-terminating outlet glaciers, which collectively drain about 22 per cent of the Greenland Ice Sheet. Using atmospheric and oceanic forcing from a mid-range future warming scenario that predicts warming by 2.8 degrees Celsius by 2100, we project a contribution of 19 to 30 millimetres to SLR from these glaciers by 2200. This contribution is largely (80 per cent) dynamic in origin and is caused by several episodic retreats past overdeepenings in outlet glacier troughs. After initial increases, however, dynamic losses from these four outlets remain relatively constant and contribute to SLR individually at rates of about 0.01 to 0.06 millimetres per year. These rates correspond to ice fluxes that are less than twice those of the late 1990s, well below previous upper bounds. For a more extreme future warming scenario (warming by 4.5 degrees Celsius by 2100), the projected losses increase by more than 50 per cent, producing a cumulative SLR of 29 to 49 millimetres by 2200.
  Nature 05/2013; 497(7448):235-8.
• Article: Immunology: Memory cells sound the alarm.

  Jennifer E Smith-Garvin, Luis J Sigal
  Nature 05/2013; 497(7448):194-6.
• Article: Forests: Oil-palm concerns in Brazilian Amazon.

  Alexander C Lees, Ima C G Vieira
  Nature 05/2013; 497(7448):188.
• Article: Studies of pear-shaped nuclei using accelerated radioactive beams.

  L P Gaffney, P A Butler, M Scheck, A B Hayes, F Wenander, M Albers, B Bastin, C Bauer, A Blazhev, S Bönig, [......], P Thoele, P Van Duppen, M J Vermeulen, M von Schmid, D Voulot, N Warr, K Wimmer, K Wrzosek-Lipska, C Y Wu, M Zielinska
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  ABSTRACT: 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 (220)Rn and (224)Ra 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.
  Nature 05/2013; 497(7448):199-204.
• Article: Discrete clouds of neutral gas between the galaxies M31 and M33.

  Spencer A Wolfe, D J Pisano, Felix J Lockman, Stacy S McGaugh, Edward J Shaya
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  ABSTRACT: Spiral galaxies must acquire gas to maintain their observed level of star formation beyond the next few billion years. A source of this material may be the gas that resides between galaxies, but our understanding of the state and distribution of this gas is incomplete. Radio observations of the Local Group of galaxies have revealed hydrogen gas extending from the disk of the galaxy M31 at least halfway to M33. This feature has been interpreted to be the neutral component of a condensing intergalactic filament, which would be able to fuel star formation in M31 and M33, but simulations suggest that such a feature could also result from an interaction between both galaxies within the past few billion years (ref. 5). Here we report radio observations showing that about 50 per cent of this gas is composed of clouds, with the rest distributed in an extended, diffuse component. The clouds have velocities comparable to those of M31 and M33, and have properties suggesting that they are unrelated to other Local Group objects. We conclude that the clouds are likely to be transient condensations of gas embedded in an intergalactic filament and are therefore a potential source of fuel for future star formation in M31 and M33.
  Nature 05/2013; 497(7448):224-6.
• Article: Galaxy formation: The cosmic web in focus.

  Robert Braun
  Nature 05/2013; 497(7448):191-2.
• Article: Oceans under surveillance.

  Quirin Schiermeier
  Nature 05/2013; 497(7448):167-8.