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  • 401. Sluijs, A
    et al.
    Schouten, S
    Pagani, M
    Woltering, M
    Brinkhuis, H
    Damste, J S S
    Dickens, G R
    Huber, M
    Reichart, G J
    Stein, R
    Matthiessen, J
    Lourens, L J
    Pedentchouk, N
    Backman, J
    Moran, K
    Scientists, Expedition 302
    Subtropical arctic ocean temperatures during the Palaeocene/Eocene thermal maximum2006In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 441, no 7093, p. 610-613Article in journal (Refereed)
    Abstract [en]

    The Palaeocene/Eocene thermal maximum, similar to 55 million years ago, was a brief period of widespread, extreme climatic warming(1-3), that was associated with massive atmospheric greenhouse gas input(4). Although aspects of the resulting environmental changes are well documented at low latitudes, no data were available to quantify simultaneous changes in the Arctic region. Here we identify the Palaeocene/Eocene thermal maximum in a marine sedimentary sequence obtained during the Arctic Coring Expedition(5). We show that sea surface temperatures near the North Pole increased from similar to 18 degrees C to over 23 degrees C during this event. Such warm values imply the absence of ice and thus exclude the influence of ice-albedo feedbacks on this Arctic warming. At the same time, sea level rose while anoxic and euxinic conditions developed in the ocean’s bottom waters and photic zone, respectively. Increasing temperature and sea level match expectations based on palaeoclimate model simulations(6), but the absolute polar temperatures that we derive before, during and after the event are more than 10 degrees C warmer than those model-predicted. This suggests that higher-than-modern greenhouse gas concentrations must have operated in conjunction with other feedback mechanisms - perhaps polar stratospheric clouds(7) or hurricane-induced ocean mixing(8) - to amplify early Palaeogene polar temperatures.

  • 402. Smartt, S. J.
    et al.
    Chen, T. -W.
    Jerkstrand, A.
    Coughlin, M.
    Kankare, E.
    Sim, S. A.
    Fraser, M.
    Inserra, C.
    Maguire, K.
    Chambers, K. C.
    Huber, M. E.
    Kruhler, T.
    Leloudas, G.
    Magee, M.
    Shingles, L. J.
    Smith, K. W.
    Young, D. R.
    Tonry, J.
    Kotak, R.
    Gal-Yam, A.
    Lyman, J. D.
    Homan, D. S.
    Agliozzo, C.
    Anderson, J. P.
    Angus, C. R.
    Ashall, C.
    Barbarino, Cristina
    Stockholm University, Faculty of Science, Department of Astronomy. Stockholm University, Faculty of Science, The Oskar Klein Centre for Cosmo Particle Physics (OKC).
    Bauer, F. E.
    Berton, M.
    Botticella, M. T.
    Bulla, Mattia
    Stockholm University, Faculty of Science, Department of Physics. Stockholm University, Faculty of Science, The Oskar Klein Centre for Cosmo Particle Physics (OKC). Inter-University Centre for Astronomy and Astrophysics (IUCAA), India.
    Bulger, J.
    Cannizzaro, G.
    Cano, Z.
    Cartier, R.
    Cikota, A.
    Clark, P.
    De Cia, A.
    Della Valle, M.
    Denneau, L.
    Dennefeld, M.
    Dessart, L.
    Dimitriadis, G.
    Elias-Rosa, N.
    Firth, R. E.
    Flewelling, H.
    Floers, A.
    Franckowiak, A.
    Frohmaier, C.
    Galbany, L.
    Gonzalez-Gaitan, S.
    Greiner, J.
    Gromadzki, M.
    Guelbenzu, A. Nicuesa
    Gutierrez, C. P.
    Hamanowicz, A.
    Hanlon, L.
    Harmanen, J.
    Heintz, K. E.
    Heinze, A.
    Hernandez, M. -S.
    Hodgkin, S. T.
    Hook, I. M.
    Izzo, L.
    James, P. A.
    Jonker, P. G.
    Kerzendorf, W. E.
    Klose, S.
    Kostrzewa-Rutkowska, Z.
    Kowalski, M.
    Kromer, M.
    Kuncarayakti, H.
    Lawrence, A.
    Lowe, T. B.
    Magnier, E. A.
    Manulis, I.
    Martin-Carrillo, A.
    Mattila, S.
    McBrien, O.
    Mueller, A.
    Nordin, J.
    O'Neill, D.
    Onori, F.
    Palmerio, J. T.
    Pastorello, A.
    Patat, F.
    Pignata, G.
    Podsiadlowski, Ph.
    Pumo, M. L.
    Prentice, S. J.
    Rau, A.
    Razza, A.
    Rest, A.
    Reynolds, T.
    Roy, Rupak
    Stockholm University, Faculty of Science, Department of Astronomy. Stockholm University, Faculty of Science, The Oskar Klein Centre for Cosmo Particle Physics (OKC).
    Ruiter, A. J.
    Rybicki, K. A.
    Salmon, L.
    Schady, P.
    Schultz, A. S. B.
    Schweyer, T.
    Seitenzahl, I. R.
    Smith, M.
    Sollerman, Jesper
    Stockholm University, Faculty of Science, Department of Astronomy. Stockholm University, Faculty of Science, The Oskar Klein Centre for Cosmo Particle Physics (OKC).
    Stalder, B.
    Stubbs, C. W.
    Sullivan, M.
    Szegedi, H.
    Taddia, Francesco
    Stockholm University, Faculty of Science, Department of Astronomy. Stockholm University, Faculty of Science, The Oskar Klein Centre for Cosmo Particle Physics (OKC).
    Taubenberger, S.
    Terreran, G.
    van Soelen, B.
    Vos, J.
    Wainscoat, R. J.
    Walton, N. A.
    Waters, C.
    Weiland, H.
    Willman, M.
    Wiseman, P.
    Wright, D. E.
    Wyrzykowski, L.
    Yaron, O.
    A kilonova as the electromagnetic counterpart to a gravitational-wave source2017In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 551, no 7678, p. 75-+Article in journal (Refereed)
    Abstract [en]

    Gravitational waves were discovered with the detection of binary black-hole mergers(1) and they should also be detectable from lower-mass neutron-star mergers. These are predicted to eject material rich in heavy radioactive isotopes that can power an electromagnetic signal. This signal is luminous at optical and infrared wavelengths and is called a kilonova(2-5). The gravitational-wave source GW170817 arose from a binary neutron-star merger in the nearby Universe with a relatively well confined sky position and distance estimate(6). Here we report observations and physical modelling of a rapidly fading electromagnetic transient in the galaxy NGC 4993, which is spatially coincident with GW170817 and with a weak, short.-ray burst(7,8). The transient has physical parameters that broadly match the theoretical predictions of blue kilonovae from neutron-star mergers. The emitted electromagnetic radiation can be explained with an ejected mass of 0.04 +/- 0.01 solar masses, with an opacity of less than 0.5 square centimetres per gram, at a velocity of 0.2 +/- 0.1 times light speed. The power source is constrained to have a power-law slope of -1.2 +/- 0.3, consistent with radioactive powering from r-process nuclides. (The r-process is a series of neutron capture reactions that synthesise many of the elements heavier than iron.) We identify line features in the spectra that are consistent with light r-process elements (atomic masses of 90-140). As it fades, the transient rapidly becomes red, and a higher-opacity, lanthanide-rich ejecta component may contribute to the emission. This indicates that neutron-star mergers produce gravitational waves and radioactively powered kilonovae, and are a nucleosynthetic source of the r-process elements.

  • 403.
    Smits, Edsger C. P.
    et al.
    University of Groningen, Netherlands; Philips Research Labs, Netherlands; Dutch Polymer Institute, Netherlands.
    Mathijssen, Simon G. J.
    Philips Research Labs, Netherlands; Eindhoven University of Technology, Netherlands.
    van Hal, Paul A.
    Philips Research Labs, Netherlands.
    Setayesh, Sepas
    Philips Research Labs, Netherlands.
    Geuns, Thomas C. T.
    Philips Research Labs, Netherlands.
    Mutsaers, Kees A. H. A.
    Philips Research Labs, Netherlands.
    Cantatore, Eugenio
    Eindhoven University of Technology, Netherlands.
    Wondergem, Harry J.
    Philips Research Labs, Netherlands.
    Werzer, Oliver
    Graz University of Technology, Austria.
    Resel, Roland
    Graz University of Technology, Austria.
    Kemerink, Martijn
    Eindhoven University of Technology, Netherlands.
    Kirchmeyer, Stephan
    HC Starck GmbH, Germany.
    Muzafarov, Aziz M.
    Russian Academic Science, Russia.
    Ponomarenko, Sergei A.
    Russian Academic Science, Russia.
    de Boer, Bert
    University of Groningen, Netherlands.
    Blom, Paul W. M.
    University of Groningen, Netherlands.
    de Leeuw, Dago M.
    University of Groningen, Netherlands; Philips Research Labs, Netherlands.
    Bottom-up organic integrated circuits2008In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 455, no 7215, p. 956-959Article in journal (Refereed)
    Abstract [en]

    Self- assembly - the autonomous organization of components into patterns and structures(1) - is a promising technology for the mass production of organic electronics. Making integrated circuits using a bottom- up approach involving self- assembling molecules was proposed(2) in the 1970s. The basic building block of such an integrated circuit is the self- assembled- monolayer field- effect transistor ( SAMFET), where the semiconductor is a monolayer spontaneously formed on the gate dielectric. In the SAMFETs fabricated so far, current modulation has only been observed in submicrometre channels(3-5), the lack of efficient charge transport in longer channels being due to defects and the limited intermolecular pi-pi coupling between the molecules in the self-assembled monolayers. Low field- effect carrier mobility, low yield and poor reproducibility have prohibited the realization of bottom- up integrated circuits. Here we demonstrate SAMFETs with long- range intermolecular pi - pi coupling in the monolayer. We achieve dense packing by using liquid- crystalline molecules consisting of a pi- conjugated mesogenic core separated by a long aliphatic chain from a monofunctionalized anchor group. The resulting SAMFETs exhibit a bulk- like carrier mobility, large current modulation and high reproducibility. As a first step towards functional circuits, we combine the SAMFETs into logic gates as inverters; the small parameter spread then allows us to combine the inverters into ring oscillators. We demonstrate real logic functionality by constructing a 15- bit code generator in which hundreds of SAMFETs are addressed simultaneously. Bridging the gap between discrete monolayer transistors and functional self-assembled integrated circuits puts bottom- up electronics in a new perspective.

  • 404. Snodgrass, Colin
    et al.
    Tubiana, Cecilia
    Vincent, Jean-Baptiste
    Sierks, Holger
    Hviid, Stubbe
    Moissl, Richard
    Boehnhardt, Hermann
    Barbieri, Cesare
    Koschny, Detlef
    Lamy, Philippe
    Rickman, Hans
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Theoretical Astrophysics.
    Rodrigo, Rafael
    Carry, Benoit
    Lowry, Stephen C.
    Laird, Ryan J. M.
    Weissman, Paul R.
    Fitzsimmons, Alan
    Marchi, Simone
    A collision in 2009 as the origin of the debris trail of asteroid P/2010 A22010In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 467, no 7317, p. 814-816Article in journal (Refereed)
    Abstract [en]

    The peculiar object P/2010 A2 was discovered(1) in January 2010 and given a cometary designation because of the presence of a trail of material, although there was no central condensation or coma. The appearance of this object, in an asteroidal orbit (small eccentricity and inclination) in the inner main asteroid belt attracted attention as a potential new member of the recently recognized(2) class of main-belt comets. If confirmed, this new object would expand the range in heliocentric distance over which main-belt comets are found. Here we report observations of P/2010 A2 by the Rosetta spacecraft. We conclude that the trail arose from a single event, rather than a period of cometary activity, in agreement with independent results(3). The trail is made up of relatively large particles of millimetre to centimetre size that remain close to the parent asteroid. The shape of the trail can be explained by an initial impact ejecting large clumps of debris that disintegrated and dispersed almost immediately. We determine that this was an asteroid collision that occurred around 10 February 2009.

  • 405.
    Sobek, Sebastian
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology.
    Climate science: Cold carbon storage2014In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 511, no 7510, p. 415-417Article in journal (Other academic)
  • 406. Soderberg, A. M.
    et al.
    Chakraborti, S.
    Pignata, G.
    Chevalier, R. A.
    Chandra, P.
    Ray, A.
    Wieringa, M. H.
    Copete, A.
    Chaplin, V.
    Connaughton, V.
    Barthelmy, S. D.
    Bietenholz, M. F.
    Chugai, N.
    Stritzinger, M. D.
    Hamuy, M.
    Fransson, Claes
    Stockholm University, Faculty of Science, Department of Astronomy.
    Fox, O.
    Levesque, E. M.
    Grindlay, J. E.
    Challis, P.
    Foley, R. J.
    Kirshner, R. P.
    Milne, P. A.
    Torres, M. A. P.
    A relativistic type Ibc supernova without a detected gamma-ray burst2010In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 463, no 7280, p. 513-515Article in journal (Refereed)
    Abstract [en]

    Long duration gamma-ray bursts (GRBs) mark(1) the explosive death of some massive stars and are a rare sub-class of type Ibc supernovae. They are distinguished by the production of an energetic and collimated relativistic outflow powered(2) by a central engine (an accreting black hole or neutron star). Observationally, this outflow is manifested(3) in the pulse of gamma-rays and a long-lived radio afterglow. Until now, central-engine driven supernovae have been discovered exclusively through their gamma-ray emission, yet it is expected(4) that a larger population goes undetected because of limited satellite sensitivity or beaming of the collimated emission away from our line of sight. In this framework, the recovery of undetected GRBs may be possible through radio searches(5,6) for type Ibc supernovae with relativistic outflows. Here we report the discovery of luminous radio emission from the seemingly ordinary type Ibc SN 2009bb, which requires a substantial relativistic outflow powered by a central engine. A comparison with our radio survey of type Ibc supernovae reveals that the fraction harbouring central engines is low, about one per cent, measured independently from, but consistent with, the inferred(7) rate of nearby GRBs. Independently, a second mildly relativistic supernova has been reported(8).

  • 407.
    Sohn, Robert A.
    et al.
    Woods Hole Oceanog Inst, Woods Hole, MA 02543 USA..
    Willis, Claire
    Woods Hole Oceanog Inst, Woods Hole, MA 02543 USA..
    Humphris, Susan
    Woods Hole Oceanog Inst, Woods Hole, MA 02543 USA..
    Shank, Timothy M.
    Woods Hole Oceanog Inst, Woods Hole, MA 02543 USA..
    Singh, Hanumant
    Woods Hole Oceanog Inst, Woods Hole, MA 02543 USA..
    Edmonds, Henrietta N.
    Univ Texas Austin, Inst Marine Sci, Port Aransas, TX 78373 USA..
    Kunz, Clayton
    Woods Hole Oceanog Inst, Woods Hole, MA 02543 USA..
    Hedman, Ulf
    Swedish Polar Secretariat, S-10405 Stockholm, Sweden..
    Helmke, Elisabeth
    Alfred Wegener Inst Polar & Marine Res, D-27570 Bremerhaven, Germany..
    Jakuba, Michael
    Johns Hopkins Univ, Baltimore, MD 21218 USA..
    Liljebladh, Bengt
    Univ Gothenburg, S-40530 Gothenburg, Sweden..
    Linder, Julia
    Alfred Wegener Inst Polar & Marine Res, D-27570 Bremerhaven, Germany..
    Murphy, Christopher
    Woods Hole Oceanog Inst, Woods Hole, MA 02543 USA..
    Nakamura, Ko-ichi
    AIST, Higashi, Tokyo, Japan..
    Sato, Taichi
    Univ Tokyo, Ocean Res Inst, Tokyo 1648639, Japan..
    Schlindwein, Vera
    Alfred Wegener Inst Polar & Marine Res, D-27570 Bremerhaven, Germany..
    Stranne, Christian
    Univ Gothenburg, S-40530 Gothenburg, Sweden..
    Tausenfreund, Maria
    Alfred Wegener Inst Polar & Marine Res, D-27570 Bremerhaven, Germany..
    Upchurch, Lucia
    Univ Texas Austin, Inst Marine Sci, Port Aransas, TX 78373 USA..
    Winsor, Peter
    Woods Hole Oceanog Inst, Woods Hole, MA 02543 USA..
    Jakobsson, Martin
    Stockholm Univ, Dept Geol & Geochem, S-10691 Stockholm, Sweden..
    Soule, Adam
    Woods Hole Oceanog Inst, Woods Hole, MA 02543 USA..
    Explosive volcanism on the ultraslow-spreading Gakkel ridge, Arctic Ocean2008In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 453, no 7199, p. 1236-1238Article in journal (Refereed)
    Abstract [en]

    Roughly 60% of the Earth's outer surface is composed of oceanic crust formed by volcanic processes at mid- ocean ridges. Although only a small fraction of this vast volcanic terrain has been visually surveyed or sampled, the available evidence suggests that explosive eruptions are rare on mid- ocean ridges, particularly at depths below the critical point for seawater ( 3,000 m)(1). A pyroclastic deposit has never been observed on the sea floor below 3,000 m, presumably because the volatile content of mid- ocean- ridge basalts is generally too low to produce the gas fractions required for fragmenting a magma at such high hydrostatic pressure. We employed new deep submergence technologies during an International Polar Year expedition to the Gakkel ridge in the Arctic Basin at 856 E, to acquire photographic and video images of 'zero- age' volcanic terrain on this remote, ice- covered ridge. Here we present images revealing that the axial valley at 4,000 m water depth is blanketed with unconsolidated pyroclastic deposits, including bubble wall fragments (limu o Pele)(2), covering a large ( > 10 km(2)) area. At least 13.5 wt% CO(2) is necessary to fragment magma at these depths(3), which is about tenfold the highest values previously measured in a mid- ocean- ridge basalt(4). These observations raise important questions about the accumulation and discharge of magmatic volatiles at ultraslow spreading rates on the Gakkel ridge(5) and demonstrate that large- scale pyroclastic activity is possible along even the deepest portions of the global mid- ocean ridge volcanic system.

  • 408.
    Soubeyran, Philippe
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research.
    Kowanetz, Katarzyna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research.
    Szymkiewcz, Iwona
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research.
    Langdon, WallaceY.
    Dikic, Ivan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research.
    Cbl-CIN85-endophilin complex mediates ligand-induced downregulation of EGF receptors2002In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 416, no 6877, p. 183-187Article in journal (Refereed)
    Abstract [en]

    Cbl is a multi-adaptor protein involved in ligand-induced downregulation of receptor tyrosine kinases. It is thought that Cbl-mediated ubiquitination of active receptors is essential for receptor degradation and cessation of receptor-induced signal transduction. Here we demonstrate that Cbl additionally regulates epidermal growth factor (EGF) receptor endocytosis. Cbl rapidly recruits CIN85 (Cbl-interacting protein of 85K; ref. 6) and endophilins (regulatory components of clathrin-coated vesicles) to form a complex with activated EGF receptors, thus controlling receptor internalization. CIN85 was constitutively associated with endophilins, whereas CIN85 binding to the distal carboxy terminus of Cbl was increased on EGF stimulation. Inhibition of these interactions was sufficient to block EGF receptor internalization, delay receptor degradation and enhance EGF-induced gene transcription, without perturbing Cbl-directed receptor ubiquitination. Thus, the evolutionary divergent C terminus of Cbl uses a mechanism that is functionally separable from the ubiquitin ligase activity of Cbl to mediate ligand-dependent downregulation of receptor tyrosine kinases.

  • 409.
    Spang, Anja
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Saw, Jimmy H.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Jorgensen, Steffen L.
    Zaremba-Niedzwiedzka, Katarzyna
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Martijn, Joran
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lind, Anders E.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    van Eijk, Roel
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Schleper, Christa
    Guy, Lionel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ettema, Thijs J. G.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Complex archaea that bridge the gap between prokaryotes and eukaryotes2015In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 521, no 7551, p. 173-179Article in journal (Refereed)
    Abstract [en]

    The origin of the eukaryotic cell remains one of the most contentious puzzles in modern biology. Recent studies have provided support for the emergence of the eukaryotic host cell from within the archaeal domain of life, but the identity and nature of the putative archaeal ancestor remain a subject of debate. Here we describe the discovery of 'Lokiarchaeota', a novel candidate archaeal phylum, which forms a monophyletic group with eukaryotes in phylogenomic analyses, and whose genomes encode an expanded repertoire of eukaryotic signature proteins that are suggestive of sophisticated membrane remodelling capabilities. Our results provide strong support for hypotheses in which the eukaryotic host evolved from a bona fide archaeon, and demonstrate that many components that underpin eukaryote-specific features were already present in that ancestor. This provided the host with a rich genomic 'starter-kit' to support the increase in the cellular and genomic complexity that is characteristic of eukaryotes.

  • 410.
    Stage, Jesper
    Department of Economics, University of Gothenburg.
    Speaking up for economic-sciences modelling2008In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 456, no 7222, p. 470-Article in journal (Other academic)
  • 411.
    Staring, Jacqueline
    et al.
    Netherlands Cancer Institute, Amsterdam, The Netherlands.
    von Castelmur, Eleonore
    Netherlands Cancer Institute, Amsterdam, The Netherlands.
    Blomen, Vincent A
    Netherlands Cancer Institute, Amsterdam, The Netherlands.
    van den Hengel, Lisa G
    Netherlands Cancer Institute, Amsterdam, The Netherlands.
    Brockmann, Markus
    Netherlands Cancer Institute, Amsterdam, The Netherlands.
    Baggen, Jim
    Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
    Thibaut, Hendrik Jan
    Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
    Nieuwenhuis, Joppe
    Netherlands Cancer Institute, Amsterdam, The Netherlands.
    Janssen, Hans
    Netherlands Cancer Institute, Amsterdam, The Netherlands.
    van Kuppeveld, Frank J M
    Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
    Perrakis, Anastassis
    Netherlands Cancer Institute, Amsterdam, The Netherlands.
    Carette, Jan E
    Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA.
    Brummelkamp, Thijn R
    Netherlands Cancer Institute, Amsterdam, The Netherlands; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria; Cancer GenomiCs.nl (CGC.nl), Amsterdam, The Netherlands.
    PLA2G16 represents a switch between entry and clearance of Picornaviridae2017In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 541, no 7637, p. 412-416Article in journal (Refereed)
    Abstract [en]

    Picornaviruses are a leading cause of human and veterinary infections that result in various diseases, including polio and the common cold. As archetypical non-enveloped viruses, their biology has been extensively studied. Although a range of different cell-surface receptors are bound by different picornaviruses, it is unclear whether common host factors are needed for them to reach the cytoplasm. Using genome-wide haploid genetic screens, here we identify the lipid-modifying enzyme PLA2G16 (refs 8, 9, 10, 11) as a picornavirus host factor that is required for a previously unknown event in the viral life cycle. We find that PLA2G16 functions early during infection, enabling virion-mediated genome delivery into the cytoplasm, but not in any virion-assigned step, such as cell binding, endosomal trafficking or pore formation. To resolve this paradox, we screened for suppressors of the ΔPLA2G16 phenotype and identified a mechanism previously implicated in the clearance of intracellular bacteria. The sensor of this mechanism, galectin-8 (encoded by LGALS8), detects permeated endosomes and marks them for autophagic degradation, whereas PLA2G16 facilitates viral genome translocation and prevents clearance. This study uncovers two competing processes triggered by virus entry: activation of a pore-activated clearance pathway and recruitment of a phospholipase to enable genome release.

  • 412. Stone, Jennifer L.
    et al.
    O'Donovan, Michael C.
    Gurling, Hugh
    Kirov, George K.
    Blackwood, Douglas H. R.
    Corvin, Aiden
    Craddock, Nick J.
    Gill, Michael
    Hultman, Christina M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Lichtenstein, Paul
    McQuillin, Andrew
    Pato, Carlos N.
    Ruderfer, Douglas M.
    Owen, Michael J.
    St Clair, David
    Sullivan, Patrick F.
    Sklar, Pamela
    Purcell, Shaun M.
    Rare chromosomal deletions and duplications increase risk of schizophrenia2008In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 455, no 7210, p. 237-241Article in journal (Refereed)
    Abstract [en]

    Schizophrenia is a severe mental disorder marked by hallucinations, delusions, cognitive deficits and apathy, with a heritability estimated at 73 - 90% ( ref. 1). Inheritance patterns are complex, and the number and type of genetic variants involved are not understood. Copy number variants ( CNVs) have been identified in individual patients with schizophrenia(2-7) and also in neurodevelopmental disorders(8-11), but large- scale genome- wide surveys have not been performed. Here we report a genome- wide survey of rare CNVs in 3,391 patients with schizophrenia and 3,181 ancestrally matched controls, using high- density microarrays. For CNVs that were observed in less than 1% of the sample and were more than 100 kilobases in length, the total burden is increased 1.15- fold in patients with schizophrenia in comparison with controls. This effect was more pronounced for rarer, single- occurrence CNVs and for those that involved genes as opposed to those that did not. As expected, deletions were found within the region critical for velo- cardio- facial syndrome, which includes psychotic symptoms in 30% of patients(12). Associations with schizophrenia were also found for large deletions on chromosome 15q13.3 and 1q21.1. These associations have not previously been reported, and they remained significant after genome- wide correction. Our results provide strong support for a model of schizophrenia pathogenesis that includes the effects of multiple rare structural variants, both genome- wide and at specific loci.

  • 413. Stuart-Smith, Rick D.
    et al.
    Bates, Amanda E.
    Lefcheck, Jonathan S.
    Duffy, J. Emmett
    Baker, Susan C.
    Thomson, Russell J.
    Stuart-Smith, Jemina F.
    Hill, Nicole A.
    Kininmonth, Stuart J.
    Stockholm University, Faculty of Science, Stockholm Resilience Centre.
    Airoldi, Laura
    Becerro, Mikel A.
    Campbell, Stuart J.
    Dawson, Terence P.
    Navarrete, Sergio A.
    Soler, German A.
    Strain, Elisabeth M. A.
    Willis, Trevor J.
    Edgar, Graham J.
    Integrating abundance and functional traits reveals new global hotspots of fish diversity2013In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 501, no 7468, p. 539-+Article in journal (Refereed)
    Abstract [en]

    Species richness has dominated our view of global biodiversity patterns for centuries(1,2). The dominance of this paradigm is reflected in the focus by ecologists and conservation managers on richness and associated occurrence-based measures for understanding drivers of broad-scale diversity patterns and as a biological basis for management(3,4). However, this is changing rapidly, as it is now recognized that not only the number of species but the species present, their phenotypes and the number of individuals of each species are critical in determining the nature and strength of the relationships between species diversity and a range of ecological functions (such as biomass production and nutrient cycling)(5). Integrating these measures should provide a more relevant representation of global biodiversity patterns in terms of ecological functions than that provided by simple species counts. Here we provide comparisons of a traditional global biodiversity distribution measure based on richness with metrics that incorporate species abundances and functional traits. We use data from standardized quantitative surveys of 2,473 marine reef fish species at 1,844 sites, spanning 133 degrees of latitude from all ocean basins, to identify new diversity hotspots in some temperate regions and the tropical eastern Pacific Ocean. These relate to high diversity of functional traits amongst individuals in the community (calculated using Rao's Q(6)), and differ from previously reported patterns in functional diversity and richness for terrestrial animals, which emphasize species-rich tropical regions only(7,8). There is a global trend for greater evenness in the number of individuals of each species, across the reef fish species observed at sites ('community evenness'), at higher latitudes. This contributes to the distribution of functional diversity hotspots and contrasts with well-known latitudinal gradients in richness(2,4). Our findings suggest that the contribution of species diversity to a range of ecosystem functions varies over large scales, and imply that in tropical regions, which have higher numbers of species, each species contributes proportionally less to community-level ecological processes on average than species in temperate regions. Metrics of ecological function usefully complement metrics of species diversity in conservation management, including when identifying planning priorities and when tracking changes to biodiversity values.

  • 414. Stuart-Smith, Rick D.
    et al.
    Edgar, Graham J.
    Barrett, Neville S.
    Kininmonth, Stuart J.
    Stockholm University, Faculty of Science, Stockholm Resilience Centre. University of Tasmania, Australia.
    Bates, Amanda E.
    Thermal biases and vulnerability to warming in the world's marine fauna2015In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 528, no 7580, p. 88-+Article in journal (Refereed)
    Abstract [en]

    A critical assumption underlying projections of biodiversity change associated with global warming is that ecological communities comprise balanced mixes of warm-affinity and cool-affinity species which, on average, approximate local environmental temperatures. Nevertheless, here we find that most shallow water marine species occupy broad thermal distributions that are aggregated in either temperate or tropical realms. These distributional trends result in ocean-scale spatial thermal biases, where communities are dominated by species with warmer or cooler affinity than local environmental temperatures. We use community-level thermal deviations from local temperatures as a form of sensitivity to warming, and combine these with projected ocean warming data to predict warming-related loss of species from present-day communities over the next century. Large changes in local species composition appear likely, and proximity to thermal limits, as inferred from present-day species' distributional ranges, outweighs spatial variation in warming rates in contributing to predicted rates of local species loss.

  • 415.
    Sun, Junliang
    et al.
    Stockholm University, Faculty of Science, Department of Physical, Inorganic and Structural Chemistry.
    Bonneau, Charlotte
    Stockholm University, Faculty of Science, Department of Physical, Inorganic and Structural Chemistry.
    Cantin, Angel
    Corma, Avelino
    Diaz-Cabanas, Maria J.
    Moliner, Manuel
    Zhang, Daliang
    Stockholm University, Faculty of Science, Department of Physical, Inorganic and Structural Chemistry.
    Li, Mingrun
    Zou, Xiaodong
    Stockholm University, Faculty of Science, Department of Physical, Inorganic and Structural Chemistry.
    The ITQ-37 mesoporous chiral zeolite2009In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 458, no 7242, p. 1154-1157Article in journal (Refereed)
    Abstract [en]

    The synthesis of crystalline molecular sieves with pore dimensions that fill the gap between microporous and mesoporous materials is a matter of fundamental and industrial interest(1-3). The preparation of zeolitic materials with extralarge pores and chiral frameworks would permit many new applications. Two important steps in this direction include the synthesis(4) of ITQ-33, a stable zeolite with 18 x 10 x 10 ring windows, and the synthesis(5) of SU-32, which has an intrinsically chiral zeolite structure and where each crystal exhibits only one handedness. Here we present a germanosilicate zeolite (ITQ-37) with extralarge 30-ring windows. Its structure was determined by combining selected area electron diffraction ( SAED) and powder X-ray diffraction (PXRD) in a charge-flipping algorithm(6). The framework follows the SrSi2 (srs) minimal net(7) and forms two unique cavities, each of which is connected to three other cavities to form a gyroidal channel system. These cavities comprise the enantiomorphous srs net of the framework. ITQ-37 is the first chiral zeolite with one single gyroidal channel. It has the lowest framework density (10.3 T atoms per 1,000 angstrom(3)) of all existing 4-coordinated crystalline oxide frameworks, and the pore volume of the corresponding silica polymorph would be 0.38 cm(3) g(-1).

  • 416.
    Sund, Johan
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational and Systems Biology.
    Andér, Martin
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Åqvist, Johan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Principles of stop-codon reading on the ribosome2010In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 465, no 7300, p. 947-U12Article in journal (Refereed)
    Abstract [en]

    In termination of protein synthesis, the bacterial release factors RF1 and RF2 bind to the ribosome through specific recognition of messenger RNA stop codons and trigger hydrolysis of the bond between the nascent polypeptide and the transfer RNA at the peptidyl-tRNA site, thereby releasing the newly synthesized protein. The release factors are highly specific for a U in the first stop-codon position 1 and recognize different combinations of purines in the second and third positions, with RF1 reading UAA and UAG and RF2 reading UAA and UGA. With recently determined crystal structures of termination complexes(2-4), it has become possible to decipher the energetics of stop-codon reading by computational analysis and to clarify the origin of the high release-factor binding accuracy. Here we report molecular dynamics free-energy calculations on different cognate and non-cognate termination complexes. The simulations quantitatively explain the basic principles of decoding in all three codon positions and reveal the key elements responsible for specificity of the release factors. The overall reading mechanism involves hitherto unidentified interactions and recognition switches that cannot be described in terms of a tripeptide anticodon model. Further simulations of complexes with tRNA(Trp), the tRNA recognizing the triplet codon for Trp, explain the observation of a 'leaky' stop codon 5 and highlight the fundamentally different third position reading by RF2, which leads to a high stop-codon specificity with strong discrimination against the Trp codon. The simulations clearly illustrate the versatility of codon reading by protein, which goes far beyond tRNA mimicry.

  • 417.
    Svedberg, The
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Philosophy, Mathematics and Science Section.
    Determination of the molecular weight of insulin1931In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 127, p. 438-439Article in journal (Refereed)
    Abstract [en]

    AT the suggestion of Dr. H. Jensen, of the Johns Hopkins University, Baltimore, an ultracentrifugal investigation of insulin has been carried out in my laboratory by Mr. B. Sjögren. A quantity of 0.25 gm. crystalline insulin was kindly put at my disposal by Dr. Jensen, and this small sample proved sufficient for a fairly complete study of the molecular weight and pH-stability region of insulin.

  • 418.
    Svensson, Lars-Håkan
    Linköping University, Faculty of Arts and Sciences. Linköping University, Department of Culture and Communication.
    An Alchemist of Our Times (Roald Hoffmann, Memory Effects)2000In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, no 22 June 2000, p. 884-885Article in journal (Other academic)
    Abstract [en]

      

  • 419.
    Säterberg, Torbjörn
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Theoretical Biology. Linköping University, The Institute of Technology.
    Sellman, Stefan
    Linköping University, Department of Physics, Chemistry and Biology, Theoretical Biology. Linköping University, The Institute of Technology.
    Ebenman, Bo
    Linköping University, Department of Physics, Chemistry and Biology, Theoretical Biology. Linköping University, The Institute of Technology.
    High frequency of functional extinctions in ecological networks2013In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 499, no 7459, p. 468-+Article in journal (Refereed)
    Abstract [en]

    Intensified exploitation of natural populations and habitats has led to increased mortality rates and decreased abundances of many species(1,2). There is a growing concern that this might cause critical abundance thresholds of species to be crossed(1,3-5), with extinction cascades and state shifts in ecosystems as a consequence(4,6,7). When increased mortality rate and decreased abundance of a given species lead to extinction of other species, this species can be characterized as functionally extinct even though it still exists. Although such functional extinctions have been observed in some ecosystems(3,4,8), their frequency is largely unknown. Here we use a new modelling approach to explore the frequency and pattern of functional extinctions in ecological networks. Specifically, we analytically derive critical abundance thresholds of species by increasing their mortality rates until an extinction occurs in the network. Applying this approach on natural and theoretical food webs, we show that the species most likely to go extinct first is not the one whose mortality rate is increased but instead another species. Indeed, up to 80% of all first extinctions are of another species, suggesting that a species ecological functionality is often lost before its own existence is threatened. Furthermore, we find that large-bodied species at the top of the food chains can only be exposed to small increases in mortality rate and small decreases in abundance before going functionally extinct compared to small-bodied species lower in the food chains. These results illustrate the potential importance of functional extinctions in ecological networks and lend strong support to arguments advocating a more community-oriented approach in conservation biology, with target levels for populations based on ecological functionality rather than on mere persistence(8-11).

  • 420. Taga, A.
    et al.
    Nordstrom, L.
    James, P.
    Johansson, Börje
    Eriksson, O.
    Non-collinear states in magnetic sensors2000In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 406, no 6793, p. 280-282Article in journal (Refereed)
  • 421. Tanvir, N. R.
    et al.
    Fox, D. B.
    Levan, A. J.
    Berger, E.
    Wiersema, K.
    Fynbo, J. P. U.
    Cucchiara, A.
    Krühler, T.
    Gehrels, N.
    Bloom, J. S.
    Greiner, J.
    Evans, P. A.
    Rol, E.
    Olivares, F.
    Hjorth, J.
    Jakobsson, P.
    Farihi, J.
    Willingale, R.
    Starling, R. L. C.
    Cenko, S. B.
    Perley, D.
    Maund, J. R.
    Duke, J.
    Wijers, R. A. M. J.
    Adamson, A. J.
    Allan, A.
    Bremer, M. N.
    Burrows, D. N.
    Castro-Tirado, A. J.
    Cavanagh, B.
    de Ugarte Postigo, A.
    Dopita, M. A.
    Fatkhullin, T. A.
    Fruchter, A. S.
    Foley, R. J.
    Gorosabel, J.
    Kennea, J.
    Kerr, T.
    Klose, S.
    Krimm, H. A.
    Komarova, V. N.
    Kulkarni, S. R.
    Moskvitin, A. S.
    Mundell, C. G.
    Naylor, T.
    Page, K.
    Penprase, B. E.
    Perri, M.
    Podsiadlowski, P.
    Roth, K.
    Rutledge, R. E.
    Sakamoto, T.
    Schady, P.
    Schmidt, B. P.
    Soderberg, A. M.
    Sollerman, J.
    Stockholm University, Faculty of Science, Department of Astronomy.
    Stephens, A. W.
    Stratta, G.
    Ukwatta, T. N.
    Watson, D.
    Westra, E.
    Wold, T.
    Wolf, C.
    A γ-ray burst at a redshift of z~8.22009In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 461, p. 1254-1257Article in journal (Refereed)
    Abstract [en]

    Long-duration γ-ray bursts (GRBs) are thought to result from the explosions of certain massive stars, and some are bright enough that they should be observable out to redshifts of z>20 using current technology. Hitherto, the highest redshift measured for any object was z = 6.96, for a Lyman-α emitting galaxy. Here we report that GRB090423 lies at a redshift of z~8.2, implying that massive stars were being produced and dying as GRBs ~630Myr after the Big Bang. The burst also pinpoints the location of its host galaxy.

  • 422. Taylor, Christopher M.
    et al.
    Belusic, Danijel
    SMHI, Research Department, Climate research - Rossby Centre.
    Guichard, Francoise
    Arker, Douglas J. P.
    Vischel, Theo
    Bock, Olivier
    Harris, Phil P.
    Janicot, Serge
    Klein, Cornelia
    Panthou, Geremy
    Frequency of extreme Sahelian storms tripled since 1982 in satellite observations2017In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 544, no 7651, p. 475-+Article in journal (Refereed)
  • 423. Teslovich, Tanya M.
    et al.
    Musunuru, Kiran
    Smith, Albert V.
    Edmondson, Andrew C.
    Stylianou, Ioannis M.
    Koseki, Masahiro
    Pirruccello, James P.
    Ripatti, Samuli
    Chasman, Daniel I.
    Willer, Cristen J.
    Johansen, Christopher T.
    Fouchier, Sigrid W.
    Isaacs, Aaron
    Peloso, Gina M.
    Barbalic, Maja
    Ricketts, Sally L.
    Bis, Joshua C.
    Aulchenko, Yurii S.
    Thorleifsson, Gudmar
    Feitosa, Mary F.
    Chambers, John
    Orho-Melander, Marju
    Melander, Olle
    Johnson, Toby
    Li, Xiaohui
    Guo, Xiuqing
    Li, Mingyao
    Cho, Yoon Shin
    Go, Min Jin
    Kim, Young Jin
    Lee, Jong-Young
    Park, Taesung
    Kim, Kyunga
    Sim, Xueling
    Ong, Rick Twee-Hee
    Croteau-Chonka, Damien C.
    Lange, Leslie A.
    Smith, Joshua D.
    Song, Kijoung
    Zhao, Jing Hua
    Yuan, Xin
    Luan, Jian'an
    Lamina, Claudia
    Ziegler, Andreas
    Zhang, Weihua
    Zee, Robert Y. L.
    Wright, Alan F.
    Witteman, Jacqueline C. M.
    Wilson, James F.
    Willemsen, Gonneke
    Wichmann, H. -Erich
    Whitfield, John B.
    Waterworth, Dawn M.
    Wareham, Nicholas J.
    Waeber, Gerard
    Vollenweider, Peter
    Voight, Benjamin F.
    Vitart, Veronique
    Uitterlinden, Andre G.
    Uda, Manuela
    Tuomilehto, Jaakko
    Thompson, John R.
    Tanaka, Toshiko
    Surakka, Ida
    Stringham, Heather M.
    Spector, Tim D.
    Soranzo, Nicole
    Smit, Johannes H.
    Sinisalo, Juha
    Silander, Kaisa
    Sijbrands, Eric J. G.
    Scuteri, Angelo
    Scott, James
    Schlessinger, David
    Sanna, Serena
    Salomaa, Veikko
    Saharinen, Juha
    Sabatti, Chiara
    Ruokonen, Aimo
    Rudan, Igor
    Rose, Lynda M.
    Roberts, Robert
    Rieder, Mark
    Psaty, Bruce M.
    Pramstaller, Peter P.
    Pichler, Irene
    Perola, Markus
    Penninx, Brenda W. J. H.
    Pedersen, Nancy L.
    Pattaro, Cristian
    Parker, Alex N.
    Pare, Guillaume
    Oostra, Ben A.
    O'Donnell, Christopher J.
    Nieminen, Markku S.
    Nickerson, Deborah A.
    Montgomery, Grant W.
    Meitinger, Thomas
    McPherson, Ruth
    McCarthy, Mark I.
    McArdle, Wendy
    Masson, David
    Martin, Nicholas G.
    Marroni, Fabio
    Mangino, Massimo
    Magnusson, Patrik K. E.
    Lucas, Gavin
    Luben, Robert
    Loos, Ruth J. F.
    Lokki, Marja-Liisa
    Lettre, Guillaume
    Langenberg, Claudia
    Launer, Lenore J.
    Lakatta, Edward G.
    Laaksonen, Reijo
    Kyvik, Kirsten O.
    Kronenberg, Florian
    Koenig, Inke R.
    Khaw, Kay-Tee
    Kaprio, Jaakko
    Kaplan, Lee M.
    Johansson, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Jarvelin, Marjo-Riitta
    Janssens, A. Cecile J. W.
    Ingelsson, Erik
    Igi, Wilmar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Hovingh, G. Kees
    Hottenga, Jouke-Jan
    Hofman, Albert
    Hicks, Andrew A.
    Hengstenberg, Christian
    Heid, Iris M.
    Hayward, Caroline
    Havulinna, Aki S.
    Hastie, Nicholas D.
    Harris, Tamara B.
    Haritunians, Talin
    Hall, Alistair S.
    Gyllensten, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Guiducci, Candace
    Groop, Leif C.
    Gonzalez, Elena
    Gieger, Christian
    Freimer, Nelson B.
    Ferrucci, Luigi
    Erdmann, Jeanette
    Elliott, Paul
    Ejebe, Kenechi G.
    Doering, Angela
    Dominiczak, Anna F.
    Demissie, Serkalem
    Deloukas, Panagiotis
    de Geus, Eco J. C.
    de Faire, Ulf
    Crawford, Gabriel
    Collins, Francis S.
    Chen, Yii-der I.
    Caulfield, Mark J.
    Campbell, Harry
    Burtt, Noel P.
    Bonnycastle, Lori L.
    Boomsma, Dorret I.
    Boekholdt, S. Matthijs
    Bergman, Richard N.
    Barroso, Ines
    Bandinelli, Stefania
    Ballantyne, Christie M.
    Assimes, Themistocles L.
    Quertermous, Thomas
    Altshuler, David
    Seielstad, Mark
    Wong, Tien Y.
    Tai, E-Shyong
    Feranil, Alan B.
    Kuzawa, Christopher W.
    Adair, Linda S.
    Taylor, Herman A., Jr.
    Borecki, Ingrid B.
    Gabriel, Stacey B.
    Wilson, James G.
    Holm, Hilma
    Thorsteinsdottir, Unnur
    Gudnason, Vilmundur
    Krauss, Ronald M.
    Mohlke, Karen L.
    Ordovas, Jose M.
    Munroe, Patricia B.
    Kooner, Jaspal S.
    Tall, Alan R.
    Hegele, Robert A.
    Kastelein, John J. P.
    Schadt, Eric E.
    Rotter, Jerome I.
    Boerwinkle, Eric
    Strachan, David P.
    Mooser, Vincent
    Stefansson, Kari
    Reilly, Muredach P.
    Samani, Nilesh J.
    Schunkert, Heribert
    Cupples, L. Adrienne
    Sandhu, Manjinder S.
    Ridker, Paul M.
    Rader, Daniel J.
    van Duijn, Cornelia M.
    Peltonen, Leena
    Abecasis, Goncalo R.
    Boehnke, Michael
    Kathiresan, Sekar
    Biological, clinical and population relevance of 95 loci for blood lipids2010In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 466, no 7307, p. 707-713Article in journal (Refereed)
    Abstract [en]

    Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P<5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.

  • 424.
    Theopold, Ulrich
    Stockholm University, Faculty of Science, Department of Molecular Biology and Functional Genomics.
    A bad boy comes good2009In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 461, p. 486-487Article, review/survey (Other (popular science, discussion, etc.))
  • 425. Thompson, Luke R.
    et al.
    Sanders, Jon G.
    McDonald, Daniel
    Amir, Amnon
    Ladau, Joshua
    Locey, Kenneth J.
    Prill, Robert J.
    Tripathi, Anupriya
    Gibbons, Sean M.
    Ackermann, Gail
    Navas-Molina, Jose A.
    Janssen, Stefan
    Kopylova, Evguenia
    Vázquez-Baeza, Yoshiki
    González, Antonio
    Morton, James T.
    Mirarab, Siavash
    Zech Xu, Zhenjiang
    Jiang, Lingjing
    Haroon, Mohamed F.
    Kanbar, Jad
    Zhu, Qiyun
    Jin Song, Se
    Kosciolek, Tomasz
    Bokulich, Nicholas A.
    Lefler, Joshua
    Brislawn, Colin J.
    Humphrey, Gregory
    Owens, Sarah M.
    Hampton-Marcell, Jarrad
    Berg-Lyons, Donna
    McKenzie, Valerie
    Fierer, Noah
    Fuhrman, Jed A.
    Clauset, Aaron
    Stevens, Rick L.
    Shade, Ashley
    Pollard, Katherine S.
    Goodwin, Kelly D.
    Jansson, Janet K.
    Gilbert, Jack A.
    Knight, Rob
    Sjöling, Sara
    Södertörn University, School of Natural Sciences, Technology and Environmental Studies, Environmental Science.
    Zhao, Hongxia
    A communal catalogue reveals Earth’s multiscale microbial diversity2017In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 551, p. 457-463Article in journal (Refereed)
    Abstract [en]

    Our growing awareness of the microbial world's importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth's microbial diversity.

  • 426.
    Thor, Stefan
    Linköping University, Department of Clinical and Experimental Medicine, Developmental Biology. Linköping University, Faculty of Health Sciences.
    Neuroscience: Light moulds plastic brains2008In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 456, no 7219, p. 177-178Article in journal (Other academic)
    Abstract [en]

    In tadpoles, the number of neurons expressing the neurotransmitter dopamine increases on exposure to light. Such plasticity might allow animals to physically match their brains’ activity to environmental stimuli.

  • 427.
    Thor, Stefan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Neuroscience: Stem cells in multiple time zones2013In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 498, no 7455, p. 441-443Article in journal (Other academic)
    Abstract [en]

    In fruitfly larvae, neural stem cells generate different cell types at different times. It emerges that these temporal progressions are controlled by multiple cascades of gene transcription factors.

  • 428.
    Thor, Stefan
    et al.
    Molecular Neurobiology Laboratory, The Salk Institute, PO Box 85800, San Diego, California 92186, USA.
    Andersson, Siv G E
    Center for Neurobiology and Behavior, Department of Genetics and Development, College of Physicians and Surgeons of Columbia University, 701 West 168th Street, New York, New York 10032, USA.
    Tomlinson, Andrew
    Center for Neurobiology and Behavior, Department of Genetics and Development, College of Physicians and Surgeons of Columbia University, 701 West 168th Street, New York, New York 10032, USA.
    Thomas, John B
    Molecular Neurobiology Laboratory, The Salk Institute, PO Box 85800, San Diego, California 92186, USA.
    A LIM-homeodomain combinatorial code for motor-neuron pathway selection.1999In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 397, no 6714, p. 76-80Article in journal (Refereed)
    Abstract [en]

    Different classes of vertebrate motor neuron that innervate distinct muscle targets express unique combinations of LIM-homeodomain transcription factors, suggesting that a combinatorial code of LIM-homeodomain proteins may underlie the control of motor-neuron pathway selection. Studies of LIM-homeodomain genes in mouse, Drosophila melanogaster and Caenorhabditis elegans have revealed functions of these genes in neuronal survival, axon guidance, neurotransmitter expression and neuronal function, but, to our knowledge, none of these studies have addressed the issue of a functional code. Here we study two members of this gene family in Drosophila, namely lim3, the homologue of the vertebrate Lhx3 and Lhx4 genes, and islet, the homologue of the vertebrate Isl1 and Is12 genes. We show that Drosophila lim3 is expressed by a specific subset of islet-expressing motor neurons and that mutating or misexpressing lim3 switches motor-neuron projections predictably. Our results provide evidence that lim3 and islet constitute a combinatorial code that generates distinct motor-neuron identities.

  • 429.
    Tinghög, Gustav
    et al.
    Linköping University, Department of Management and Engineering, Economics. Linköping University, Faculty of Arts and Sciences. Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Health Sciences.
    Andersson, David
    Linköping University, Department of Management and Engineering, Economics. Linköping University, Faculty of Arts and Sciences.
    Bonn, Caroline
    University of Innsbruck, Austria.
    Böttiger, Harald
    Klarna AB, Stockholm, Sweden.
    Josephson, Camilla
    Linköping University, Department of Management and Engineering, Economics. Linköping University, Faculty of Arts and Sciences.
    Lundgren, Gustaf
    Stockholm School of Economics, Sweden.
    Västfjäll, Daniel
    Linköping University, Department of Behavioural Sciences and Learning. Linköping University, Faculty of Arts and Sciences.
    Kirchler, Michael
    University of Innsbruck, Austria.
    Johannesson, Magnus
    Linköping University, Department of Management and Engineering, Economics. Linköping University, Faculty of Arts and Sciences.
    Intuition and cooperation reconsidered2013In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 498, no 7452, p. E1-E2Article in journal (Refereed)
    Abstract [en]

    Rand et al.1 reported increased cooperation in social dilemmas after forcing individuals to decide quickly1. Time pressure was used to induce intuitive decisions, and they concluded that intuition promotes cooperation. We test the robustness of this finding in a series of five experiments involving about 2,500 subjects in three countries. None of the experiments confirms the Rand et al.1 finding, indicating that their result was an artefact of excluding the about 50% of subjects who failed to respond on time.

  • 430.
    Tiselius, Arne
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Philosophy, Mathematics and Science Section.
    Diffusion of water in a zeolite crystal1934In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 133, p. 212-213Article in journal (Refereed)
    Abstract [en]

    I have made an attempt to study this migration quantitatively. For this purpose I have chosen an optical method, which makes a direct observation of the migration possible.

  • 431. Toledo-Arana, Alejandro
    et al.
    Dussurget, Olivier
    Nikitas, Georgios
    Sesto, Nina
    Guet-Revillet, Hélène
    Balestrino, Damien
    Loh, Edmund
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Gripenland, Jonas
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Tiensuu, Teresa
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Vaitkevicius, Karolis
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Barthelemy, Mathieu
    Vergassola, Massimo
    Nahori, Marie-Anne
    Soubigou, Guillaume
    Régnault, Béatrice
    Coppée, Jean-Yves
    Lecuit, Marc
    Johansson, Jörgen
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Cossart, Pascale
    The Listeria transcriptional landscape from saprophytism to virulence2009In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 459, no 7249, p. 950-956Article in journal (Refereed)
    Abstract [en]

    The bacterium Listeria monocytogenes is ubiquitous in the environment and can lead to severe food-borne infections. It has recently emerged as a multifaceted model in pathogenesis. However, how this bacterium switches from a saprophyte to a pathogen is largely unknown. Here, using tiling arrays and RNAs from wild-type and mutant bacteria grown in vitro, ex vivo and in vivo, we have analysed the transcription of its entire genome. We provide the complete Listeria operon map and have uncovered far more diverse types of RNAs than expected: in addition to 50 small RNAs (<500 nucleotides), at least two of which are involved in virulence in mice, we have identified antisense RNAs covering several open-reading frames and long overlapping 5' and 3' untranslated regions. We discovered that riboswitches can act as terminators for upstream genes. When Listeria reaches the host intestinal lumen, an extensive transcriptional reshaping occurs with a SigB-mediated activation of virulence genes. In contrast, in the blood, PrfA controls transcription of virulence genes. Remarkably, several non-coding RNAs absent in the non-pathogenic species Listeria innocua exhibit the same expression patterns as the virulence genes. Together, our data unravel successive and coordinated global transcriptional changes during infection and point to previously unknown regulatory mechanisms in bacteria.

  • 432. Tong, L. M.
    et al.
    Gattass, R. R.
    Ashcom, J. B.
    He, Sailing
    Lou, J. Y.
    Shen, M. Y.
    Maxwell, I.
    Mazur, E.
    Subwavelength-diameter silica wires for low-loss optical wave guiding2003In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 426, no 6968, p. 816-819Article in journal (Refereed)
  • 433. Traas, J.
    et al.
    Bellini, C.
    Nacry, P.
    Kronenberger, J.
    Bouchez, D.
    Caboche, M.
    Normal Differentiation Pattern in Plants Lacking Microtubular Preprophase Bands1995In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 375, no 6533, p. 676-677Article in journal (Refereed)
    Abstract [en]

    IT is generally accepted that polarized cell expansion and the strict control of division plane alignment are prerequisites for ordered spatial development in higher plants(1). This appears to be linked to the presence of cell walls, which immobilize the cells and fix their relative positions. In this context, the cortical cytoskeleton is thought to play a central role(1-6). Interphase microtubules are often aligned perpendicular to the growth axis and it has been proposed that they control cell expansion, probably in combination with the cell wall. Another cytoskeletal array, the prephophase band, has been associated with division plane alignment. This structure, which girdles the cell at the G2 phase of the cell cycle and at prophase, precisely predicts the future division site and probably fixes it. Here we describe different mutants in Arabidopsis that are unable to form these two cortical microtubular arrays. As expected, this defect is associated with irregular cell expansion and the inability to align division planes. Surprisingly, however, the mutations do not affect differentiation patterns: all cell types and organs are in their correct relative positions.

  • 434. Tröstl, Jasmin
    et al.
    Chuang, Wayne K.
    Gordon, Hamish
    Heinritzi, Martin
    Yan, Chao
    Molteni, Ugo
    Ahlm, Lars
    Stockholm University, Faculty of Science, Department of Applied Environmental Science (ITM).
    Frege, Carla
    Bianchi, Federico
    Wagner, Robert
    Simon, Mario
    Lehtipalo, Katrianne
    Williamson, Christina
    Craven, Jill S.
    Duplissy, Jonathan
    Adamov, Alexey
    Almeida, Joao
    Bernhammer, Anne-Kathrin
    Breitenlechner, Martin
    Brilke, Sophia
    Dias, Antònio
    Ehrhart, Sebastian
    Flagan, Richard C.
    Franchin, Alessandro
    Fuchs, Claudia
    Guida, Roberto
    Gysel, Martin
    Hansel, Armin
    Hoyle, Christopher R.
    Jokinen, Tuija
    Junninen, Heikki
    Kangasluoma, Juha
    Keskinen, Helmi
    Kim, Jaeseok
    Krapf, Manuel
    Kürten, Andreas
    Laaksonen, Ari
    Lawler, Michael
    Leiminger, Markus
    Mathot, Serge
    Möhler, Ottmar
    Nieminen, Tuomo
    Onnela, Antti
    Petäjä, Tuukka
    Piel, Felix M.
    Miettinen, Pasi
    Rissanen, Matti P.
    Rondo, Linda
    Sarnela, Nina
    Schobesberger, Siegfried
    Sengupta, Kamalika
    Sipilä, Mikko
    Smith, James N.
    Steiner, Gerhard
    Tomè, Antònio
    Virtanen, Annele
    Wagner, Andrea C.
    Weingartner, Ernest
    Wimmer, Daniela
    Winkler, Paul M.
    Ye, Penglin
    Carslaw, Kenneth S.
    Curtius, Joachim
    Dommen, Josef
    Kirkby, Jasper
    Kulmala, Markku
    Riipinen, Ilona
    Stockholm University, Faculty of Science, Department of Applied Environmental Science (ITM).
    Worsnop, Douglas R.
    Donahue, Neil M.
    Baltensperger, Urs
    The role of low-volatility organic compounds in initial particle growth in the atmosphere2016In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 533, no 7604, p. 527-531Article in journal (Refereed)
    Abstract [en]

    About half of present-day cloud condensation nuclei originate from atmospheric nucleation, frequently appearing as a burst of new particles near midday(1). Atmospheric observations show that the growth rate of new particles often accelerates when the diameter of the particles is between one and ten nanometres(2,3). In this critical size range, new particles are most likely to be lost by coagulation with pre-existing particles(4), thereby failing to form new cloud condensation nuclei that are typically 50 to 100 nanometres across. Sulfuric acid vapour is often involved in nucleation but is too scarce to explain most subsequent growth(5,6), leaving organic vapours as the most plausible alternative, at least in the planetary boundary layer(7-10). Although recent studies(11-13) predict that low-volatility organic vapours contribute during initial growth, direct evidence has been lacking. The accelerating growth may result from increased photolytic production of condensable organic species in the afternoon(2), and the presence of a possible Kelvin (curvature) effect, which inhibits organic vapour condensation on the smallest particles (the nano-Kohler theory)(2,14), has so far remained ambiguous. Here we present experiments performed in a large chamber under atmospheric conditions that investigate the role of organic vapours in the initial growth of nucleated organic particles in the absence of inorganic acids and bases such as sulfuric acid or ammonia and amines, respectively. Using data from the same set of experiments, it has been shown(15) that organic vapours alone can drive nucleation. We focus on the growth of nucleated particles and find that the organic vapours that drive initial growth have extremely low volatilities (saturation concentration less than 10(-4.5) micrograms per cubic metre). As the particles increase in size and the Kelvin barrier falls, subsequent growth is primarily due to more abundant organic vapours of slightly higher volatility (saturation concentrations of 10(-4.5) to 10(-0.5) micrograms per cubic metre). We present a particle growth model that quantitatively reproduces our measurements. Furthermore, we implement a parameterization of the first steps of growth in a global aerosol model and find that concentrations of atmospheric cloud concentration nuclei can change substantially in response, that is, by up to 50 per cent in comparison with previously assumed growth rate parameterizations.

  • 435.
    Turner, Anthony P. F.
    Cranfield University, UK.
    Biosensors: Switching channels makes sense1997In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 387, no 6633, p. 555-557Article in journal (Other academic)
  • 436. Uhlen, P.
    et al.
    Laestadius, A.
    Jahnukainen, T.
    Soderblom, T.
    Backhed, F.
    Celsi, G.
    Brismar, Hjalmar
    Normark, S.
    Aperia, A.
    Richter-Dahlfors, A.
    alpha-Haemolysin of uropathogenic E-coli induces Ca2+ oscillations in renal epithelial cells2000In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 405, no 6787, p. 694-697Article in journal (Refereed)
    Abstract [en]

    Pyelonephritis is one of the most common febrile diseases in children. If not treated appropriately, it causes irreversible renal damage and accounts for a large proportion of end stage renal failures(1). Renal scarring can occur in the absence of inflammatory cells, indicating that bacteria may have a direct signalling effect on renal cells(2). Intracellular calcium ([Ca2+](i)) oscillations can protect cells from the cytotoxic effects of prolonged increases in intracellular calcium(3,4). However, no pathophysiologically relevant protein that induces such oscillations has been identified. Here we show that infection by uropathogenic Escherichia coli induces a constant, low-frequency oscillatory [Ca2+](i) response in target primary rat renal epithelial cells induced by the secreted RTX (repeats-in-toxin) toxin alpha-haemolysin. The response depends on calcium influx through L-type calcium channels as well as from internal stores gated by inositol triphosphate. Internal calcium oscillations induced by alpha-haemolysin in a renal epithelial cell line stimulated production of cytokines interleukin (IL)-6 and IL-8. Our findings indicate a novel role for alpha-haemolysin in pyelonephritis: as an inducer of an oscillating second messenger response in target cells, which fine-tunes gene expression during the inflammatory response.

  • 437.
    Vanlandewijck, Michael
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology. Karolinska Inst, AstraZeneca Integrated Cardio Metab Ctr KI AZ ICM, Blickagangen 6, SE-14157 Huddinge, Sweden..
    He, Liqun
    Tianjin Med Univ, Key Lab Postneuroinjury Neurorepair & Regenerat C, Dept Neurosurg,Gen Hosp, Tianjin Neurol Inst,Minist Educ & Tianjin City, Tianjin 300052, Peoples R China..
    Mäe, Maarja Andaloussi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    Andrae, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    Ando, Koji
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    Del Gaudio, Francesca
    Karolinska Inst, Dept Cell & Mol Biol, Von Eulers Vag 3, SE-17177 Stockholm, Sweden..
    Nahar, Khayrun
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    Lebouvier, Thibaud
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Univ Lille, CHU,Memory Ctr, Distalz, Inserm,U1171, F-59000 Lille, France..
    Laviña, Bàrbara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    Gouveia, Maria Leonor Seguardo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    Sun, Ying
    Zhongyuan Union Genet Technol Co Ltd, Dept Bioinformat, Tianjin Airport Econ Area, 45 9th East Rd, Tianjin 300304, Peoples R China..
    Raschpergert, Elisabeth
    Karolinska Inst, AstraZeneca Integrated Cardio Metab Ctr KI AZ ICM, Blickagangen 6, SE-14157 Huddinge, Sweden..
    Räsänen, Markus
    Univ Helsinki, Wihuri Res Inst, Haartmaninkatu 8,POB 63, FI-00014 Helsinki, Finland.;Univ Helsinki, Translat Canc Biol Program, Biomedicum Helsinki, Haartmaninkatu 8,POB 63, FI-00014 Helsinki, Finland..
    Zarb, Yvette
    Zurich Univ, Univ Zurich Hosp, Div Neurosurg, CH-8091 Zurich, Switzerland..
    Mochizuki, Naoki
    Natl Cerebral & Cardiovasc Ctr, Dept Cell Biol, Res Inst, Suita, Osaka, Japan.;Natl Cerebral & Cardiovasc Ctr, AMED CREST, Suita, Osaka, Japan..
    Keller, Annika
    Zurich Univ, Univ Zurich Hosp, Div Neurosurg, CH-8091 Zurich, Switzerland..
    Lendahl, Urban
    Karolinska Inst, Dept Cell & Mol Biol, Von Eulers Vag 3, SE-17177 Stockholm, Sweden..
    Betsholtz, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology. Karolinska Inst, AstraZeneca Integrated Cardio Metab Ctr KI AZ ICM, Blickagangen 6, SE-14157 Huddinge, Sweden.
    A molecular atlas of cell types and zonation in the brain vasculature2018In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 554, no 7693, p. 475-480Article in journal (Refereed)
    Abstract [en]

    Cerebrovascular disease is the third most common cause of death in developed countries, but our understanding of the cells that compose the cerebral vasculature is limited. Here, using vascular single-cell transcriptomics, we provide molecular definitions for the principal types of blood vascular and vessel-associated cells in the adult mouse brain. We uncover the transcriptional basis of the gradual phenotypic change (zonation) along the arteriovenous axis and reveal unexpected cell type differences: a seamless continuum for endothelial cells versus a punctuated continuum for mural cells. We also provide insight into pericyte organotypicity and define a population of perivascular fibroblast-like cells that are present on all vessel types except capillaries. Our work illustrates the power of single-cell transcriptomics to decode the higher organizational principles of a tissue and may provide the initial chapter in a molecular encyclopaedia of the mammalian vasculature.

  • 438. Vincent, Jean-Baptiste
    et al.
    Bodewits, Dennis
    Besse, Sebastien
    Sierks, Holger
    Barbieri, Cesare
    Lamy, Philippe
    Rodrigo, Rafael
    Koschny, Detlef
    Rickman, Hans
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Theoretical Astrophysics.
    Keller, Horst Uwe
    Agarwal, Jessica
    A'Hearn, Michael F.
    Auger, Anne-Therese
    Barucci, M. Antonella
    Bertaux, Jean-Loup
    Bertini, Ivano
    Capanna, Claire
    Cremonese, Gabriele
    Da Deppo, Vania
    Davidsson, Bjoern
    Debei, Stefano
    De Cecco, Mariolino
    El-Maarry, Mohamed Ramy
    Ferri, Francesca
    Fornasier, Sonia
    Fulle, Marco
    Gaskell, Robert
    Giacomini, Lorenza
    Groussin, Olivier
    Guilbert-Lepoutre, Aurelie
    Gutierrez-Marques, P.
    Gutierrez, Pedro J.
    Guettler, Carsten
    Hoekzema, Nick
    Hoefner, Sebastian
    Hviid, Stubbe F.
    Ip, Wing-Huen
    Jorda, Laurent
    Knollenberg, Joerg
    Kovacs, Gabor
    Kramm, Rainer
    Kuehrt, Ekkehard
    Kueppers, Michael
    La Forgia, Fiorangela
    Lara, Luisa M.
    Lazzarin, Monica
    Lee, Vicky
    Leyrat, Cedric
    Lin, Zhong-Yi
    Lopez Moreno, Jose J.
    Lowry, Stephen
    Magrin, Sara
    Maquet, Lucie
    Marchi, Simone
    Marzari, Francesco
    Massironi, Matteo
    Michalik, Harald
    Moissl, Richard
    Mottola, Stefano
    Naletto, Giampiero
    Oklay, Nilda
    Pajola, Maurizio
    Preusker, Frank
    Scholten, Frank
    Thomas, Nicolas
    Toth, Imre
    Tubiana, Cecilia
    Large heterogeneities in comet 67P as revealed by active pits from sinkhole collapse2015In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 523, no 7558, p. 63-66Article in journal (Refereed)
    Abstract [en]

    Pits have been observed on many cometary nuclei mapped by spacecraft(1-4). It has been argued that cometary pits are a signature of endogenic activity, rather than impact craters such as those on planetary and asteroid surfaces. Impact experiments(5,6) andmodels(7,8) cannot reproduce the shapes of most of the observed cometary pits, and the predicted collision rates imply that few of the pits are related to impacts(8,9). Alternative mechanisms like explosive activity(10) have been suggested, but the driving process remains unknown. Here we report that pits on comet 67P/Churyumov-Gerasimenko are active, and probably created by a sinkhole process, possibly accompanied by outbursts. We argue that after formation, pits expand slowly in diameter, owing to sublimation-driven retreat of the walls. Therefore, pits characterize how eroded the surface is: a fresh cometary surface will have a ragged structure with many pits, while an evolved surface will look smoother. The size and spatial distribution of pits imply that large heterogeneities exist in the physical, structural or compositional properties of the first few hundred metres below the current nucleus surface.

  • 439.
    Virtanen, Anders
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Pettersson, U.
    Le Moullec, J.M.
    Tiollais, P.
    Perricaudet, M.
    Different mRNAs from the transforming region (EIB) of highly- and non-oncogenic human adenoviruses1982In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 295, no 5851, p. 705-707Article in journal (Refereed)
  • 440. Virtanen, Annele
    et al.
    Joutsensaari, Jorma
    Koop, Thomas
    Kannosto, Jonna
    Yli-Pirila, Pasi
    Leskinen, Jani
    Makela, Jyrki M.
    Holopainen, Jarmo K.
    Poeschl, Ulrich
    Kulmala, Markku
    Stockholm University, Faculty of Science, Department of Applied Environmental Science (ITM).
    Worsnop, Douglas R.
    Laaksonen, Ari
    An amorphous solid state of biogenic secondary organic aerosol particles2010In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 467, no 7317, p. 824-827Article in journal (Refereed)
    Abstract [en]

    Secondary organic aerosol (SOA) particles are formed in the atmosphere from condensable oxidation products of anthropogenic and biogenic volatile organic compounds (VOCs)(1-7). On a global scale, biogenic VOCs account for about 90% of VOC emissions(1,8) and of SOA formation (90 billion kilograms of carbon per year)(1-4). SOA particles can scatter radiation and act as cloud condensation or ice nuclei, and thereby influence the Earth's radiation balance and climate(1,2,5,9,10). They consist of a myriad of different compounds with varying physicochemical properties, and little information is available on the phase state of SOA particles. Gas-particle partitioning models usually assume that SOA particles are liquid(1,5,11), but here we present experimental evidence that they can be solid under ambient conditions. We investigated biogenic SOA particles formed from oxidation products of VOCs in plant chamber experiments and in boreal forests within a few hours after atmospheric nucleation events. On the basis of observed particle bouncing in an aerosol impactor and of electron microscopy we conclude that biogenic SOA particles can adopt an amorphous solid-most probably glassy-state. This amorphous solid state should provoke a rethinking of SOA processes because it may influence the partitioning of semi-volatile compounds, reduce the rate of heterogeneous chemical reactions, affect the particles' ability to accommodate water and act as cloud condensation or ice nuclei, and change the atmospheric lifetime of the particles(12-15). Thus, the results of this study challenge traditional views of the kinetics and thermodynamics of SOA formation and transformation in the atmosphere and their implications for air quality and climate.

  • 441. Vonk, J. E.
    et al.
    Sanchez-Garcia, L.
    van Dongen, B. E.
    Alling, V.
    Kosmach, D.
    Charkin, A.
    Semiletov, I. P.
    Dudarev, O. V.
    Shakhova, N.
    Roos, P.
    Eglinton, T. I.
    Andersson, A.
    Gustafsson, Ö.
    Activation of old carbon by erosion of coastal and subsea permafrost in Arctic Siberia2012In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 489Article in journal (Refereed)
    Abstract [en]

    The future trajectory of greenhouse gas concentrations depends on interactions between climate and the biogeosphere(1,2). Thawing of Arctic permafrost could release significant amounts of carbon into the atmosphere in this century(3). Ancient Ice Complex deposits outcropping along the similar to 7,000-kilometre-long coastline of the East Siberian Arctic Shelf (ESAS)(4,5), and associated shallow subsea permafrost(6,7), are two large pools of permafrost carbon(8), yet their vulnerabilities towards thawing and decomposition are largely unknown(9-11). Recent Arctic warming is stronger than has been predicted by several degrees, and is particularly pronounced over the coastal ESAS region(12,13). There is thus a pressing need to improve our understanding of the links between permafrost carbon and climate in this relatively inaccessible region. Here we show that extensive release of carbon from these Ice Complex deposits dominates (57 +/- 2 per cent) the sedimentary carbon budget of the ESAS, the world's largest continental shelf, overwhelming the marine and topsoil terrestrial components. Inverse modelling of the dual-carbon isotope composition of organic carbon accumulating in ESAS surface sediments, using Monte Carlo simulations to account for uncertainties, suggests that 44 +/- 10 teragrams of old carbon is activated annually from Ice Complex permafrost, an order of magnitude more than has been suggested by previous studies(14). We estimate that about two-thirds (66 +/- 16 per cent) of this old carbon escapes to the atmosphere as carbon dioxide, with the remainder being re-buried in shelf sediments. Thermal collapse and erosion of these carbon-rich Pleistocene coastline and seafloor deposits may accelerate with Arctic amplification of climate warming(2,13).

  • 442.
    Vonk, J. E.
    et al.
    Stockholm University, Faculty of Science, Department of Applied Environmental Science (ITM).
    Sanchez-Garcia, Laura
    Stockholm University, Faculty of Science, Department of Applied Environmental Science (ITM).
    van Dongen, B. E.
    Stockholm University, Faculty of Science, Department of Applied Environmental Science (ITM).
    Alling, V.
    Stockholm University, Faculty of Science, Department of Applied Environmental Science (ITM).
    Kosmach, D.
    Charkin, A.
    Semiletov, I. P.
    Dudarev, O. V.
    Shakhova, N.
    Roos, P.
    Eglinton, T. I.
    Andersson, A.
    Stockholm University, Faculty of Science, Department of Applied Environmental Science (ITM).
    Gustafsson, O.
    Stockholm University, Faculty of Science, Department of Applied Environmental Science (ITM).
    Activation of old carbon by erosion of coastal and subsea permafrost in Arctic Siberia2012In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 489, no 7414, p. 137-140Article in journal (Refereed)
    Abstract [en]

    The future trajectory of greenhouse gas concentrations depends on interactions between climate and the biogeosphere(1,2). Thawing of Arctic permafrost could release significant amounts of carbon into the atmosphere in this century(3). Ancient Ice Complex deposits outcropping along the similar to 7,000-kilometre-long coastline of the East Siberian Arctic Shelf (ESAS)(4,5), and associated shallow subsea permafrost(6,7), are two large pools of permafrost carbon(8), yet their vulnerabilities towards thawing and decomposition are largely unknown(9-11). Recent Arctic warming is stronger than has been predicted by several degrees, and is particularly pronounced over the coastal ESAS region(12,13). There is thus a pressing need to improve our understanding of the links between permafrost carbon and climate in this relatively inaccessible region. Here we show that extensive release of carbon from these Ice Complex deposits dominates (57 +/- 2 per cent) the sedimentary carbon budget of the ESAS, the world's largest continental shelf, overwhelming the marine and topsoil terrestrial components. Inverse modelling of the dual-carbon isotope composition of organic carbon accumulating in ESAS surface sediments, using Monte Carlo simulations to account for uncertainties, suggests that 44 +/- 10 teragrams of old carbon is activated annually from Ice Complex permafrost, an order of magnitude more than has been suggested by previous studies(14). We estimate that about two-thirds (66 +/- 16 per cent) of this old carbon escapes to the atmosphere as carbon dioxide, with the remainder being re-buried in shelf sediments. Thermal collapse and erosion of these carbon-rich Pleistocene coastline and seafloor deposits may accelerate with Arctic amplification of climate warming(2,13).

  • 443. Wagner, W
    et al.
    Torgerson, H
    Einsiedel, E
    Jelsoe, E
    Fredrickson, H
    Lassen, J
    Rusanen, T
    Boy, D
    de Cheveigné, S
    Hampel, J
    Stathopoulou, A
    Allansdottir, A
    Midden, C
    Nielsen, T
    Przestalski, A
    Twardowski, T
    Fjæstad, Björn
    Mid Sweden University, Faculty of Human Sciences, Department of Social Sciences.
    Olsson [Öhman], Susanna
    Mid Sweden University, Faculty of Human Sciences, Department of Social Sciences.
    Olofsson, Anna
    Mid Sweden University, Faculty of Human Sciences, Department of Social Sciences.
    Gaskell, George
    Durant, J
    Bauer, M
    Liakopoulos, M
    Europe ambivalent on biotechnology1997In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 387, p. 845-847Article in journal (Refereed)
    Abstract [en]

    The Eurobarometer on Biotechnology (46.1) was conducted during October and November 1996. The survey conducted in each EU (European Union) country used a multi-stage random sampling procedure and provided a statistically representative sample of national residents aged 15 and over. The total sample within the EU was 16,246 respondents (about 1,000 per EU country). The survey questionnaire was designed by the authors as part of a larger study involving the comparative analysis of public perceptions, media coverage and public policy in relation to biotechnology from 1973 to the present.

  • 444.
    Wahl, Simone
    et al.
    Res Unit Mol Epidemiol, German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Inst Epidemiol II, German Res Ctr Environm Hlth, Helmholtz Zentrum M nchen, Neuherberg, Germany.;German Ctr Diabet Res DZD, Neuherberg, Germany.;Univ Alexandria, Med Res Inst, Clin & Expt Surg Dept, Hadara, Alexandria 21561, Egypt..
    Drong, Alexander
    Univ Oxford, Wellcome Trust Ctr Human Genet, Roosevelt Dr, Oxford OX3 7BN, England..
    Lehne, Benjamin
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostatist, MRC PHE Ctr Environm & Hlth, London W2 1PG, England..
    Loh, Marie
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostatist, MRC PHE Ctr Environm & Hlth, London W2 1PG, England.;Inst Hlth Sci, POB 5000, FI-90014 Oulu, Finland.;Translat Lab Genet Med TLGM, Agcy Sci, Technol & Res ASTAR, 8A Biomed Grove, Singapore 138648, Singapore..
    Scott, William R.
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostatist, MRC PHE Ctr Environm & Hlth, London W2 1PG, England.;Imperial Coll London, Natl Heart & Lung Inst, London W12 0NN, England..
    Kunze, Sonja
    Res Unit Mol Epidemiol, German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Inst Epidemiol II, German Res Ctr Environm Hlth, Helmholtz Zentrum M nchen, Neuherberg, Germany..
    Tsai, Pei-Chien
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England..
    Ried, Janina S.
    German Res Ctr Environm Hlth, Inst Genet Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany..
    Zhang, Weihua
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostatist, MRC PHE Ctr Environm & Hlth, London W2 1PG, England.;Imperial Coll London, Natl Heart & Lung Inst, London W12 0NN, England.;Ealing Hosp NHS Trust, Middlesex UB1 3HW, England..
    Yang, Youwen
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostatist, MRC PHE Ctr Environm & Hlth, London W2 1PG, England..
    Tan, Sili
    Fiorito, Giovanni
    Human Genet Fdn Torino, Turin, Italy.;Univ Torino, Dept Med Sci, Turin, Italy..
    Franke, Lude
    Univ Med Ctr Groningen, Dept Genet, NL-9700 RB Groningen, Netherlands.;Univ Groningen, NL-9700 AB Groningen, Netherlands..
    Guarrera, Simonetta
    Human Genet Fdn Torino, Turin, Italy.;Univ Torino, Dept Med Sci, Turin, Italy..
    Kasela, Silva
    Univ Tartu, Estonian Genome Ctr, Riia 23b, EE-51010 Tartu, Estonia.;Univ Tartu, Inst Mol & Cell Biol, Dept Biotechnol, Riia 23, EE-51010 Tartu, Estonia..
    Kriebel, Jennifer
    Res Unit Mol Epidemiol, German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Inst Epidemiol II, German Res Ctr Environm Hlth, Helmholtz Zentrum M nchen, Neuherberg, Germany.;German Ctr Diabet Res DZD, Neuherberg, Germany..
    Richmond, Rebecca C.
    Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England..
    Adamo, Marco
    Univ Coll London Hosp, UCLH Bariatr Ctr Weight Loss, Weight Management & Metab & Endocrine Surg, Ground Floor West Wing,250 Euston Rd, London NW1 2PG, England..
    Afzal, Uzma
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostatist, MRC PHE Ctr Environm & Hlth, London W2 1PG, England.;Imperial Coll London, Natl Heart & Lung Inst, London W12 0NN, England.;Ealing Hosp NHS Trust, Middlesex UB1 3HW, England..
    Ala-Korpela, Mika
    Univ Oulu & Biocenter Oulu, Computat Med, Fac Med, Oulu, Finland.;Univ Eastern Finland, Sch Pharm, NMR Metabol Lab, Kuopio, Finland.;Univ Bristol & Med Res Council Integrat Epidemiol, Univ Bristol, Sch Social & Community Med, Computat Med, Bristol, Avon, England..
    Albetti, Benedetta
    Univ Studi Milano & Fondazione IRCCS CaGranda Osp, Dept Clin Sci & Community Hlth, EPIGET Lab, Milan, Italy..
    Ammerpohl, Ole
    Univ Hosp Schleswig Holstein, Inst Human Genet, Kiel Campus, Kiel, Germany..
    Apperley, Jane F.
    Imperial Coll London, Dept Med, Centre Haematol, Fac Med, Hammersmith Campus, London W12 0NN, England..
    Beekman, Marian
    Leiden Univ Med Ctr, Mol Epidemiol, NL-2333 ZC Leiden, Netherlands..
    Bertazzi, Pier Alberto
    Univ Studi Milano & Fondazione IRCCS CaGranda Osp, Dept Clin Sci & Community Hlth, EPIGET Lab, Milan, Italy..
    Black, S. Lucas
    Imperial Coll London, Dept Med, Sect Infect Dis & Immun, London W12 0NN, England..
    Blancher, Christine
    Bonder, Marc-Jan
    Univ Med Ctr Groningen, Dept Genet, NL-9700 RB Groningen, Netherlands.;Univ Groningen, NL-9700 AB Groningen, Netherlands..
    Brosch, Mario
    Univ Oxford, High Throughput Genom Oxford Genom Ctr, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.;Tech Univ Dresden, Univ Hosp, Med Dept 1, Dresden, Germany..
    Carstensen-Kirberg, Maren
    Heinrich Heine Univ Dusseldorf, German Diabet Ctr, Leibniz Ctr Diabet Res, Inst Clin Diabetol, Dusseldorf, Germany..
    de Craen, Anton J. M.
    Leiden Univ Med Ctr, Gerontol & Geriatr, NL-2300 RC Leiden, Netherlands..
    de Lusignan, Simon
    Univ Surrey, Dept Clin & Expt Med, Guildford GU2 7PX, Surrey, England..
    Dehghan, Abbas
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Elkalaawy, Mohamed
    Univ Coll London Hosp, UCLH Bariatr Ctr Weight Loss, Weight Management & Metab & Endocrine Surg, Ground Floor West Wing,250 Euston Rd, London NW1 2PG, England.;Univ Alexandria, Med Res Inst, Clin & Expt Surg Dept, Hadara, Alexandria 21561, Egypt..
    Fischer, Krista
    Univ Tartu, Estonian Genome Ctr, Riia 23b, EE-51010 Tartu, Estonia..
    Franco, Oscar H.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Gaunt, Tom R.
    Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England..
    Hampe, Jochen
    Univ Oxford, High Throughput Genom Oxford Genom Ctr, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England..
    Hashemi, Majid
    Univ Coll London Hosp, UCLH Bariatr Ctr Weight Loss, Weight Management & Metab & Endocrine Surg, Ground Floor West Wing,250 Euston Rd, London NW1 2PG, England..
    Isaacs, Aaron
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Jenkinson, Andrew
    Univ Coll London Hosp, UCLH Bariatr Ctr Weight Loss, Weight Management & Metab & Endocrine Surg, Ground Floor West Wing,250 Euston Rd, London NW1 2PG, England..
    Jha, Sujeet
    Dept Endocrinol, Diabet & Obes, Max Healthcare, New Delhi 110017, India..
    Kato, Norihiro
    Res Inst, Natl Ctr Global Hlth & Med, Dept Gene Diagnost & Therapeut, Tokyo 1628655, Japan..
    Krogh, Vittorio
    Epidemiol & Prevent Unit, Fondazione IRCSS Ist Nazl Tumori, Milan, Italy..
    Laffan, Michael
    Imperial Coll London, Dept Med, Centre Haematol, Fac Med, Hammersmith Campus, London W12 0NN, England..
    Meisinger, Christa
    Inst Epidemiol II, German Res Ctr Environm Hlth, Helmholtz Zentrum M nchen, Neuherberg, Germany..
    Meitinger, Thomas
    German Res Ctr Environm Hlth, Int Human Genet, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Tech Univ Munich, Inst Human Genet, Munich, Germany.;Partner site Munich Heart Alliance, DZHK German Ctr Cardiovasc Res, Munich, Germany..
    Mok, Zuan Yu
    Natl Univ Singapore, Cancer Sci Inst Singapore, Singapore, Singapore..
    Motta, Valeria
    Univ Studi Milano & Fondazione IRCCS CaGranda Osp, Dept Clin Sci & Community Hlth, EPIGET Lab, Milan, Italy.;Partner site Munich Heart Alliance, DZHK German Ctr Cardiovasc Res, Munich, Germany..
    Ng, Hong Kiat
    Natl Univ Singapore, Cancer Sci Inst Singapore, Singapore, Singapore..
    Nikolakopoulou, Zacharoula
    Natl Heart & Lung Inst, London SW3 6LY, England..
    Nteliopoulos, Georgios
    Imperial Coll London, Dept Med, Centre Haematol, Fac Med, Hammersmith Campus, London W12 0NN, England..
    Panico, Salvatore
    Dipartmento Med Clin Chirurgia Federio II Univ, Naples, Italy..
    Pervjakova, Natalia
    Univ Tartu, Estonian Genome Ctr, Riia 23b, EE-51010 Tartu, Estonia.;Univ Tartu, Inst Mol & Cell Biol, Dept Biotechnol, Riia 23, EE-51010 Tartu, Estonia..
    Prokisch, Holger
    Tech Univ Munich, Inst Human Genet, Munich, Germany..
    Rathmann, Wolfgang
    Heinrich Heine Univ Dusseldorf, German Diabet Ctr, Leibniz Ctr Diabet Res, Inst Biometr & Epidemiol, Dusseldorf, Germany..
    Roden, Michael
    German Ctr Diabet Res DZD, Neuherberg, Germany.;Heinrich Heine Univ Dusseldorf, German Diabet Ctr, Leibniz Ctr Diabet Res, Inst Clin Diabetol, Dusseldorf, Germany.;Heinrich Heine Univ Hosp Dusseldorf, Fac Med, Dept Endocrinol & Diabetol, Dusseldorf, Germany..
    Rota, Federica
    Univ Studi Milano & Fondazione IRCCS CaGranda Osp, Dept Clin Sci & Community Hlth, EPIGET Lab, Milan, Italy..
    Rozario, Michelle Ann
    Sandling, Johanna K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab. Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Hinxton, England..
    Schafmayer, Clemens
    Univ Hosp Schleswig Holstein, Dept Visceral & Thorac Surg, Kiel Campus, Kiel, Germany..
    Schramm, Katharina
    Tech Univ Munich, Inst Human Genet, Munich, Germany..
    Siebert, Reiner
    Univ Hosp Schleswig Holstein, Inst Human Genet, Kiel Campus, Kiel, Germany.;Univ Hosp Ulm, Inst Human Genet, Albert Einstein Allee 11, D-89081 Ulm, Germany..
    Slagboom, P. Eline
    Leiden Univ Med Ctr, Mol Epidemiol, NL-2333 ZC Leiden, Netherlands..
    Soininen, Pasi
    Univ Oulu & Biocenter Oulu, Computat Med, Fac Med, Oulu, Finland.;Univ Eastern Finland, Sch Pharm, NMR Metabol Lab, Kuopio, Finland..
    Stolk, Lisette
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands..
    Strauch, Konstantin
    German Res Ctr Environm Hlth, Inst Genet Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Ludwig Maximilians Univ Munchen, Inst Med Informat, Biometry & Epidemiol, Chair Genet Epidemiol, Munich, Germany..
    Tai, E-Shyong
    Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore 119228, Singapore.;Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117597, Singapore.;Duke Natl Univ, Singapore Grad Med Sch, Singapore 169857, Singapore..
    Tarantini, Letizia
    Univ Studi Milano & Fondazione IRCCS CaGranda Osp, Dept Clin Sci & Community Hlth, EPIGET Lab, Milan, Italy..
    Thorand, Barbara
    Inst Epidemiol II, German Res Ctr Environm Hlth, Helmholtz Zentrum M nchen, Neuherberg, Germany.;German Ctr Diabet Res DZD, Neuherberg, Germany..
    Tigchelaar, Ettje F.
    Univ Med Ctr Groningen, Dept Genet, NL-9700 RB Groningen, Netherlands.;Univ Groningen, NL-9700 AB Groningen, Netherlands..
    Tumino, Rosario
    Cancer Registry & Histopathol Unit, Civile MP Arezzo Hosp, ASP 7, Ragusa, Italy..
    Uitterlinden, Andre G.
    Erasmus MC, Dept Internal Med & Epidemiol, Rotterdam, Netherlands..
    van Duijn, Cornelia
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    van Meurs, Joyce B. J.
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands..
    Vineis, Paolo
    Imperial Coll London, Epidemiol & Publ Hlth, London, England..
    Wickremasinghe, Ananda Rajitha
    Univ Kelaniya, Dept Publ Hlth, Fac Med, Box 6,Thalagolla Rd, Ragama 11010, Sri Lanka..
    Wijmenga, Cisca
    Univ Med Ctr Groningen, Dept Genet, NL-9700 RB Groningen, Netherlands.;Univ Groningen, NL-9700 AB Groningen, Netherlands..
    Yang, Tsun-Po
    Yuan, Wei
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England.;Inst Canc Res, Surrey SM2 5NG, England..
    Zhernakova, Alexandra
    Univ Med Ctr Groningen, Dept Genet, NL-9700 RB Groningen, Netherlands.;Univ Groningen, NL-9700 AB Groningen, Netherlands..
    Batterham, Rachel L.
    Univ Coll London Hosp, UCLH Bariatr Ctr Weight Loss, Weight Management & Metab & Endocrine Surg, Ground Floor West Wing,250 Euston Rd, London NW1 2PG, England.;UCL, Rayne Inst, Dept Med, Ctr Obes Res, London WC1E 6JJ, England..
    Smith, George Davey
    Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England..
    Deloukas, Panos
    Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London EC1M 6BQ, England.;King Abdulaziz Univ, Princess Jawhara Brahim Ctr Excellence Res Heredi, Jeddah 21589, Saudi Arabia..
    Heijmans, Bastiaan T.
    Herder, Christian
    German Ctr Diabet Res DZD, Neuherberg, Germany.;Heinrich Heine Univ Dusseldorf, German Diabet Ctr, Leibniz Ctr Diabet Res, Inst Clin Diabetol, Dusseldorf, Germany..
    Hofman, Albert
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Lindgren, Cecilia M.
    Broad Inst, Massachusetts Inst Technol & Harvard Univ, Cambridge, MA 02142 USA..
    Milani, Lili
    Univ Tartu, Estonian Genome Ctr, Riia 23b, EE-51010 Tartu, Estonia..
    van der Harst, Pim
    Univ Med Ctr Groningen, Dept Cardiol, Univ Groningen, NL-9700 RB Groningen, Netherlands.;ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, NL-3511 GC Utrecht, Netherlands..
    Peters, Annette
    German Ctr Diabet Res DZD, Neuherberg, Germany.;Partner site Munich Heart Alliance, DZHK German Ctr Cardiovasc Res, Munich, Germany..
    Illig, Thomas
    Res Unit Mol Epidemiol, German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Hannover Med Sch, Hannover Unified Biobank, Feodor Lynen St 15, Hannover, Germany.;Hannover Med Sch, Inst Human Genet, Carl Neuberg St 1, Hannover, Germany..
    Relton, Caroline L.
    Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England..
    Waldenberger, Melanie
    Res Unit Mol Epidemiol, German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Inst Epidemiol II, German Res Ctr Environm Hlth, Helmholtz Zentrum M nchen, Neuherberg, Germany..
    Jaervelin, Marjo-Riitta
    Imperial Coll London, Sch Publ Hlth, MRC Hlth Protect Agcy HPE Ctr Environm & Hlth, Dept Epidemiol & Biostatist, London, England.;Univ Oulu, Bioctr Oulu, POB 5000, Oulu, Finland.;Univ Oulu, Ctr Life Course Epidemiol, Fac Med, POB 5000, Oulu 90014, Finland.;Oulu Univ Hosp, Unit Primary Care, Kajaanintie 50,Box 20, Oulu, Finland..
    Bollati, Valentina
    Univ Studi Milano & Fondazione IRCCS CaGranda Osp, Dept Clin Sci & Community Hlth, EPIGET Lab, Milan, Italy..
    Soong, Richie
    Natl Univ Singapore, Cancer Sci Inst Singapore, Singapore, Singapore.;Natl Univ Singapore Hosp, Dept Pathol, Singapore, Singapore..
    Spector, Tim D.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England..
    Scott, James
    Imperial Coll London, Natl Heart & Lung Inst, London W12 0NN, England..
    McCarthy, Mark I.
    Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Oxford NIHR Biomed Res Ctr, Churchill Hosp, Oxford OX3 7LJ, England..
    Elliott, Paul
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostatist, MRC PHE Ctr Environm & Hlth, London W2 1PG, England..
    Bell, Jordana T.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England..
    Matullo, Giuseppe
    Human Genet Fdn Torino, Turin, Italy.;Univ Torino, Dept Med Sci, Turin, Italy..
    Gieger, Christian
    Res Unit Mol Epidemiol, German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Inst Epidemiol II, German Res Ctr Environm Hlth, Helmholtz Zentrum M nchen, Neuherberg, Germany..
    Kooner, Jaspal S.
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostatist, MRC PHE Ctr Environm & Hlth, London W2 1PG, England.;Imperial Coll London, Natl Heart & Lung Inst, London W12 0NN, England.;Ealing Hosp NHS Trust, Middlesex UB1 3HW, England.;Imperial Coll Healthcare NHS Trust, London W12 0HS, England..
    Grallert, Harald
    Res Unit Mol Epidemiol, German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Inst Epidemiol II, German Res Ctr Environm Hlth, Helmholtz Zentrum M nchen, Neuherberg, Germany.;German Ctr Diabet Res DZD, Neuherberg, Germany.;Imperial Coll London, Natl Heart & Lung Inst, London W12 0NN, England..
    Chambers, John C.
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostatist, MRC PHE Ctr Environm & Hlth, London W2 1PG, England.;Imperial Coll London, Natl Heart & Lung Inst, London W12 0NN, England.;Ealing Hosp NHS Trust, Middlesex UB1 3HW, England.;Imperial Coll Healthcare NHS Trust, London W12 0HS, England.;Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore, Singapore..
    Epigenome-wide association study of body mass index, and the adverse outcomes of adiposity2017In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 541, no 7635, p. 81-+Article in journal (Refereed)
    Abstract [en]

    Approximately 1.5 billion people worldwide are overweight or affected by obesity, and are at risk of developing type (2) diabetes, cardiovascular disease and related metabolic and inflammatory disturbances(1,2). Although the mechanisms linking adiposity to associated clinical conditions are poorly understood, recent studies suggest that adiposity may influence DNA methylation(3-6), a key regulator of gene expression and molecular phenotype(7). Here we use epigenome-wide association to show that body mass index (BMI; a key measure of adiposity) is associated with widespread changes in DNA methylation (187 genetic loci with P < 1 x 10(-7), range P = 9.2 x 10(-8) to 6.0 x 10(-46); n = 10,261 samples). Genetic association analyses demonstrate that the alterations in DNA methylation are predominantly the consequence of adiposity, rather than the cause. We find that methylation loci are enriched for functional genomic features in multiple tissues (P < 0.05), and show that sentinel methylation markers identify gene expression signatures at 38 loci (P < 9.0 x 10(-6), range P = 5.5 x 10(-6) to 6.1 x 10(-35), n = 1,785 samples). The methylation loci identify genes involved in lipid and lipoprotein metabolism, substrate transport and inflammatory pathways. Finally, we show that the disturbances in DNA methylation predict future development of type 2 diabetes (relative risk per 1 standard deviation increase in methylation risk score: 2.3 (2.07-2.56); P = 1.1 x 10(-54)). Our results provide new insights into the biologic pathways influenced by adiposity, and may enable development of new strategies for prediction and prevention of type 2 diabetes and other adverse clinical consequences of obesity.

  • 445. Wang, Jian
    et al.
    Krejci, Radovan
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
    Giangrandel, Scott
    Kuang, Chongai
    Barbosa, Henrique M. J.
    Brito, Joel
    Carbone, Samara
    Chi, Xuguang
    Comstock, Jennifer
    Ditas, Florian
    Lavric, Jost
    Manninen, Hanna E.
    Mei, Fan
    Moran-Zuloaga, Daniel
    Poehlker, Christopher
    Poehlker, Mira L.
    Saturno, Jorge
    Schmid, Beat
    Souza, Rodrigo A. F.
    Springston, Stephen R.
    Tomlinson, Jason M.
    Toto, Tami
    Walter, David
    Wimmer, Daniela
    Smith, James N.
    Kulmala, Markku
    Machado, Luiz A. T.
    Artaxo, Paulo
    Andreae, Meinrat O.
    Petaja, Tuukka
    Martin, Scot T.
    Amazon boundary layer aerosol concentration sustained by vertical transport during rainfall2016In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 539, no 7629, p. 416-419Article in journal (Refereed)
    Abstract [en]

    The nucleation of atmospheric vapours is an important source of new aerosol particles that can subsequently grow to form cloud condensation nuclei in the atmosphere(1). Most field studies of atmospheric aerosols over continents are influenced by atmospheric vapours of anthropogenic origin (for example, ref. 2) and, in consequence, aerosol processes in pristine, terrestrial environments remain poorly understood. The Amazon rainforest is one of the few continental regions where aerosol particles and their precursors can be studied under near-natural conditions(3-5), but the origin of small aerosol particles that grow into cloud condensation nuclei in the Amazon boundary layer remains unclear(6-8). Here we present aircraft- and ground-based measurements under clean conditions during the wet season in the central Amazon basin. We find that high concentrations of small aerosol particles (with diameters of less than 50 nanometres) in the lower free troposphere are transported from the free troposphere into the boundary layer during precipitation events by strong convective downdrafts and weaker downward motions in the trailing stratiform region. This rapid vertical transport can help to maintain the population of particles in the pristine Amazon boundary layer, and may therefore influence cloud properties and climate under natural conditions.

  • 446. Wang, Kaituo
    et al.
    Sitsel, Oleg
    Meloni, Gabriele
    Autzen, Henriette Elisabeth
    Andersson, Magnus
    KTH, School of Engineering Sciences (SCI), Theoretical Physics, Theoretical & Computational Biophysics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Klymchuk, Tetyana
    Nielsen, Anna Marie
    Rees, Douglas C.
    Nissen, Poul
    Gourdon, Pontus
    Structure and mechanism of Zn2+-transporting P-type ATPases2014In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 514, no 7523, p. 518-+Article in journal (Refereed)
    Abstract [en]

    Zinc is an essential micronutrient for all living organisms. It is required for signalling and proper functioning of a range of proteins involved in, for example, DNA binding and enzymatic catalysis(1). In prokaryotes and photosynthetic eukaryotes, Zn2+-transporting P-type ATPases of class IB (ZntA) are crucial for cellular redistribution and detoxification of Zn2+ and related elements(2,3). Here we present crystal structures representing the phosphoenzyme ground state (E2P) and a dephosphorylation intermediate (E2.P-i) of ZntA from Shigella sonnei, determined at 3.2 angstrom and 2.7 angstrom resolution, respectively. The structures reveal a similar fold to Cu+-ATPases, with an amphipathic helix at the membrane interface. A conserved electronegative funnel connects this region to the intramembranous high-affinity ion-binding site and may promote specific uptake of cellular Zn2+ ions by the transporter. The E2P structure displays a wide extracellular release pathway reaching the invariant residues at the high-affinity site, including C392, C394 and D714. The pathway closes in the E2.P-i state, in which D714 interacts with the conserved residue K693, which possibly stimulates Zn2+ release as a built-in counter ion, as has been proposed for H+-ATPases. Indeed, transport studies in liposomes provide experimental support for ZntA activity without counter transport. These findings suggest a mechanistic link between P-IB-type Zn2+-ATPases and P-III-type H+-ATPases and at the same time show structural features of the extracellular release pathway that resemble P-II-type ATPases such as the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase(4,5) (SERCA) and Na+, K+-ATPase(6). These findings considerably increase our understanding of zinc transport in cells and represent new possibilities for biotechnology and biomedicine.

  • 447. Wang, Yingdi
    et al.
    Nakayama, Masanori
    Pitulescu, Mara E
    Schmidt, Tim S
    Bochenek, Magdalena L
    Sakakibara, Akira
    Adams, Susanne
    Davy, Alice
    Deutsch, Urban
    Lüthi, Urs
    Barberis, Alcide
    Benjamin, Laura E
    Mäkinen, Taija
    Nobes, Catherine D
    Adams, Ralf H
    Ephrin-B2 controls VEGF-induced angiogenesis and lymphangiogenesis.2010In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 465, no 7297Article in journal (Refereed)
    Abstract [en]

    In development, tissue regeneration or certain diseases, angiogenic growth leads to the expansion of blood vessels and the lymphatic vasculature. This involves endothelial cell proliferation as well as angiogenic sprouting, in which a subset of cells, termed tip cells, acquires motile, invasive behaviour and extends filopodial protrusions. Although it is already appreciated that angiogenesis is triggered by tissue-derived signals, such as vascular endothelial growth factor (VEGF) family growth factors, the resulting signalling processes in endothelial cells are only partly understood. Here we show with genetic experiments in mouse and zebrafish that ephrin-B2, a transmembrane ligand for Eph receptor tyrosine kinases, promotes sprouting behaviour and motility in the angiogenic endothelium. We link this pro-angiogenic function to a crucial role of ephrin-B2 in the VEGF signalling pathway, which we have studied in detail for VEGFR3, the receptor for VEGF-C. In the absence of ephrin-B2, the internalization of VEGFR3 in cultured cells and mutant mice is defective, which compromises downstream signal transduction by the small GTPase Rac1, Akt and the mitogen-activated protein kinase Erk. Our results show that full VEGFR3 signalling is coupled to receptor internalization. Ephrin-B2 is a key regulator of this process and thereby controls angiogenic and lymphangiogenic growth.

  • 448. Warren, Wesley C
    et al.
    Clayton, David F
    Ellegren, Hans
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Arnold, Arthur P
    Hillier, Ladeana W
    Künstner, Axel
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics.
    Searle, Steve
    White, Simon
    Vilella, Albert J
    Fairley, Susan
    Heger, Andreas
    Kong, Lesheng
    Ponting, Chris P
    Jarvis, Erich D
    Mello, Claudio V
    Minx, Pat
    Lovell, Peter
    Velho, Tarciso A F
    Ferris, Margaret
    Balakrishnan, Christopher N
    Sinha, Saurabh
    Blatti, Charles
    London, Sarah E
    Li, Yun
    Lin, Ya-Chi
    George, Julia
    Sweedler, Jonathan
    Southey, Bruce
    Gunaratne, Preethi
    Watson, Michael
    Nam, Kiwoong
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics.
    Backström, Niclas
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics.
    Smeds, Linnea
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics.
    Nabholz, Benoit
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics.
    Itoh, Yuichiro
    Whitney, Osceola
    Pfenning, Andreas R
    Howard, Jason
    Völker, Martin
    Skinner, Bejamin M
    Griffin, Darren K
    Ye, Liang
    McLaren, William M
    Flicek, Paul
    Quesada, Victor
    Velasco, Gloria
    Lopez-Otin, Carlos
    Puente, Xose S
    Olender, Tsviya
    Lancet, Doron
    Smit, Arian F A
    Hubley, Robert
    Konkel, Miriam K
    Walker, Jerilyn A
    Batzer, Mark A
    Gu, Wanjun
    Pollock, David D
    Chen, Lin
    Cheng, Ze
    Eichler, Evan E
    Stapley, Jessica
    Slate, Jon
    Ekblom, Robert
    Birkhead, Tim
    Burke, Terry
    Burt, David
    Scharff, Constance
    Adam, Iris
    Richard, Hugues
    Sultan, Marc
    Soldatov, Alexey
    Lehrach, Hans
    Edwards, Scott V
    Yang, Shiaw-Pyng
    Li, Xiaoching
    Graves, Tina
    Fulton, Lucinda
    Nelson, Joanne
    Chinwalla, Asif
    Hou, Shunfeng
    Mardis, Elaine R
    Wilson, Richard K
    The genome of a songbird2010In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 464, no 7289, p. 757-762Article in journal (Refereed)
    Abstract [en]

    The zebra finch is an important model organism in several fields with unique relevance to human neuroscience. Like other songbirds, the zebra finch communicates through learned vocalizations, an ability otherwise documented only in humans and a few other animals and lacking in the chicken-the only bird with a sequenced genome until now. Here we present a structural, functional and comparative analysis of the genome sequence of the zebra finch (Taeniopygia guttata), which is a songbird belonging to the large avian order Passeriformes. We find that the overall structures of the genomes are similar in zebra finch and chicken, but they differ in many intrachromosomal rearrangements, lineage-specific gene family expansions, the number of long-terminal-repeat-based retrotransposons, and mechanisms of sex chromosome dosage compensation. We show that song behaviour engages gene regulatory networks in the zebra finch brain, altering the expression of long non-coding RNAs, microRNAs, transcription factors and their targets. We also show evidence for rapid molecular evolution in the songbird lineage of genes that are regulated during song experience. These results indicate an active involvement of the genome in neural processes underlying vocal communication and identify potential genetic substrates for the evolution and regulation of this behaviour.

  • 449. Wedemeyer-Bohm, Sven
    et al.
    Scullion, Eamon
    Steiner, Oskar
    van der Voort, Luc Rouppe
    de la Cruz Rodriguez, Jaime
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Theoretical Astrophysics.
    Fedun, Viktor
    Erdelyi, Robert
    Magnetic tornadoes as energy channels into the solar corona2012In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 486, no 7404, p. 505-508Article in journal (Refereed)
    Abstract [en]

    Heating the outer layers of the magnetically quiet solar atmosphere to more than one million kelvin and accelerating the solar wind requires an energy flux of approximately 100 to 300 watts per square metre(1-6), but how this energy is transferred and dissipated there is a puzzle and several alternative solutions have been proposed. Braiding and twisting of magnetic field structures, which is caused by the convective flows at the solar surface, was suggested as an efficient mechanism for atmospheric heating(7). Convectively driven vortex flows that harbour magnetic fields are observed(8-10) to be abundant in the photosphere (the visible surface of the Sun). Recently, corresponding swirling motions have been discovered(11) in the chromosphere, the atmospheric layer sandwiched between the photosphere and the corona. Here we report the imprints of these chromospheric swirls in the transition region and low corona, and identify them as observational signatures of rapidly rotating magnetic structures. These ubiquitous structures, which resemble super-tornadoes under solar conditions, reach from the convection zone into the upper solar atmosphere and provide an alternative mechanism for channelling energy from the lower into the upper solar atmosphere.

  • 450. Wernet, Philippe
    et al.
    Kunnus, Kristjan
    Josefsson, Ida
    Stockholm University, Faculty of Science, Department of Physics.
    Rajkovic, Ivan
    Quevedo, Wilson
    Beye, Martin
    Schreck, Simon
    Grübel, Sebastian
    Scholz, Mirko
    Nordlund, Dennis
    Zhang, Wenkai
    Hartsock, Robert W.
    Schlotter, William F.
    Turner, Joshua J.
    Kennedy, Brian
    Hennies, Frank
    de Groot, Frank M. F.
    Gaffney, Kelly J.
    Techert, Simone
    Odelius, Michael
    Stockholm University, Faculty of Science, Department of Physics.
    Föhlisch, Alexander
    Orbital-specific mapping of the ligand exchange dynamics of Fe(CO)5 in solution2015In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 520, no 7545, p. 78-81Article in journal (Refereed)
    Abstract [en]

    Transition-metal complexes have long attracted interest for fundamental chemical reactivity studies and possible use in solar energy conversion. Electronic excitation, ligand loss from the metal centre, or a combination of both, creates changes in charge and spin density at the metal site that need to be controlled to optimize complexes for photocatalytic hydrogen production and selective carbon-hydrogen bond activation. An understanding at the molecular level of how transition-metal complexes catalyse reactions, and in particular of the role of the short-lived and reactive intermediate states involved, will be critical for such optimization. However, suitable methods for detailed characterization of electronic excited states have been lacking. Here we show, with the use of X-ray laser-based femtosecond resolution spectroscopy and advanced quantum chemical theory to probe the reaction dynamics of the benchmark transition-metal complex Fe(CO)5 insolution, that the photoinduced removal of CO generates the 16-electron Fe(CO)4 species, a homogeneous catalyst with an electron deficiency at the Fe centre, in a hitherto unreported excited singlet state that either converts to the triplet ground state or combines with a CO or solvent molecule to regenerate a penta-coordinated Fe species on a sub-picosecond timescale. This finding, which resolves the debate about the relative importance of different spin channels in the photochemistry of Fe(CO)5 (refs 4, 16,17,18,19 and 20), was made possible by the ability of femtosecond X-ray spectroscopy to probe frontier-orbital interactions with atom specificity. We expect the method to be broadly applicable in the chemical sciences, and to complement approaches that probe structural dynamics in ultrafast processes.

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