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  • 1.
    Abellán, C.
    et al.
    ICFO - Institut de Ciencies Fotoniques, The Barcelona Institute of Science and Technology, Barcelona, Spain.
    Acín, A.
    ICFO - Institut de Ciencies Fotoniques, The Barcelona Institute of Science and Technology, Barcelona, Spain / ICREA - Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain.
    Alarcón, A.
    Millennium Institute for Research in Optics, Universidad de Concepción, Universidad de Concepción, Concepción, Chile / Departamento de Ingeniería Eléctrica, Universidad de Concepción, Concepción, Chile.
    Alibart, O.
    Université Côte d’Azur, CNRS UMR 7010, Institut de Physique de Nice (INPHYNI), Nice, France.
    Andersen, C. K.
    Department of Physics, ETH Zurich,, Zurich, Switzerland.
    Andreoli, F.
    Dipartimento di Fisica, Sapienza Università di Roma, Rome, Italy.
    Beckert, A.
    Department of Physics, ETH Zurich,, Zurich, Switzerland.
    Beduini, F. A.
    ICFO - Institut de Ciencies Fotoniques, The Barcelona Institute of Science and Technology, Barcelona, Spain.
    Bendersky, A.
    Departamento de Computación, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires and Instituto de Investigación en Ciencias de la Comunicación (ICC), CONICET, Buenos Aires, Argentina.
    Bentivegna, M.
    Dipartimento di Fisica, Sapienza Università di Roma, Rome, Italy.
    Bierhorst, P.
    National Institute of Standards and Technology, Boulder, CO, USA.
    Burchardt, D.
    Ludwig-Maximilians-Universität, Munich, Germany.
    Cabello, A.
    Departamento de Física Aplicada II, Universidad de Sevilla, Seville, Spain.
    Cariñe, J.
    Millennium Institute for Research in Optics, Universidad de Concepción, Universidad de Concepción, Concepción, Chile.
    Carrasco, S.
    ICFO - Institut de Ciencies Fotoniques, The Barcelona Institute of Science and Technology, Barcelona, Spain.
    Carvacho, G.
    Dipartimento di Fisica, Sapienza Università di Roma, Rome, Italy.
    Cavalcanti, D.
    Chaves, R.
    Cortés-Vega, J.
    Cuevas, A.
    Delgado, A.
    de Riedmatten, H.
    Eichler, C.
    Farrera, P.
    Fuenzalida, J.
    García-Matos, M.
    Garthoff, R.
    Gasparinetti, S.
    Gerrits, T.
    Ghafari Jouneghani, F.
    Glancy, S.
    Gómez, E. S.
    González, P.
    Guan, J. -Y.
    Handsteiner, J.
    Heinsoo, J.
    Heintze, G.
    Hirschmann, A.
    Jiménez, O.
    Kaiser, F.
    Knill, E.
    Knoll, L. T.
    Krinner, S.
    Kurpiers, P.
    Larotonda, M. A.
    Larsson, Jan-Åke
    Linköping University, Department of Electrical Engineering, Information Coding. Linköping University, Faculty of Science & Engineering.
    Lenhard, A.
    Li, H.
    Li, M. -H.
    Lima, G.
    Liu, B.
    Liu, Y.
    López Grande, I. H.
    Lunghi, T.
    Ma, X.
    Magaña-Loaiza, O. S.
    Magnard, P.
    Magnoni, A.
    Martí­-Prieto, M.
    Martínez, D.
    Mataloni, P.
    Mattar, A.
    Mazzera, M.
    Mirin, R. P.
    Mitchell, M. W.
    Nam, S.
    Oppliger, M.
    Pan, J. -W.
    Patel, R. B.
    Pryde, G. J.
    Rauch, D.
    Redeker, K.
    Rieländer, D.
    Ringbauer, M.
    Roberson, T.
    Rosenfeld, W.
    Salathé, Y.
    Santodonato, L.
    Sauder, G.
    Scheidl, T.
    Schmiegelow, C. T.
    Sciarrino, F.
    Seri, A.
    Shalm, L. K.
    Shi, S. -C
    Slussarenko, S.
    Stevens, M. J.
    Tanzilli, S.
    Toledo, F.
    Tura, J.
    Ursin, R.
    Vergyris, P.
    Verma, V. B.
    Walter, T.
    Wallraff, A.
    Wang, Z.
    Weinfurter, H.
    Weston, M. M.
    White, A. G.
    Wu, C.
    Xavier, Guilherme B.
    Linköping University, Department of Electrical Engineering, Information Coding. Linköping University, Faculty of Science & Engineering.
    You, L.
    Yuan, X.
    Zeilinger, A.
    Zhang, Q.
    Zhang, W.
    Zhong, J.
    Challenging Local Realism with Human Choices2018In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 557, p. 212-216Article in journal (Refereed)
    Abstract [en]

    A Bell test is a randomized trial that compares experimental observations against the philosophical worldview of local realism , in which the properties of the physical world are independent of our observation of them and no signal travels faster than light. A Bell test requires spatially distributed entanglement, fast and high-efficiency detection and unpredictable measurement settings. Although technology can satisfy the first two of these requirements, the use of physical devices to choose settings in a Bell test involves making assumptions about the physics that one aims to test. Bell himself noted this weakness in using physical setting choices and argued that human ‘free will’ could be used rigorously to ensure unpredictability in Bell tests. Here we report a set of local-realism tests using human choices, which avoids assumptions about predictability in physics. We recruited about 100,000 human participants to play an online video game that incentivizes fast, sustained input of unpredictable selections and illustrates Bell-test methodology. The participants generated 97,347,490 binary choices, which were directed via a scalable web platform to 12 laboratories on five continents, where 13 experiments tested local realism using photons, single atoms, atomic ensembles and superconducting devices. Over a 12-hour period on 30 November 2016, participants worldwide provided a sustained data flow of over 1,000 bits per second to the experiments, which used different human-generated data to choose each measurement setting. The observed correlations strongly contradict local realism and other realistic positions in bi-partite and tri-partite 12 scenarios. Project outcomes include closing the ‘freedom-of-choice loophole’ (the possibility that the setting choices are influenced by ‘hidden variables’ to correlate with the particle properties), the utilization of video-game methods for rapid collection of human-generated randomness, and the use of networking techniques for global participation in experimental science.

  • 2.
    Bai, Sai
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, Faculty of Science & Engineering. Univ Oxford, England.
    Da, Peimei
    Univ Oxford, England.
    Li, Cheng
    Univ Bayreuth, Germany; Xiamen Univ, Peoples R China.
    Wang, Zhiping
    Univ Oxford, England.
    Yuan, Zhongcheng
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Fu, Fan
    Empa-Swiss Federal Laboratories for Materials Science and Technology, Duebendorf, Switzerland.
    Kawecki, Maciej
    Empa, Switzerland; Univ Basel, Switzerland.
    Liu, Xianjie
    Linköping University, Department of Physics, Chemistry and Biology, Surface Physics and Chemistry. Linköping University, Faculty of Science & Engineering.
    Sakai, Nobuya
    Univ Oxford, England.
    Wang, Jacob Tse-Wei
    CSIRO Energy, Australia.
    Huettner, Sven
    Univ Bayreuth, Germany.
    Buecheler, Stephan
    Empa Swiss Fed Labs Mat Sci and Technol, Switzerland.
    Fahlman, Mats
    Linköping University, Department of Physics, Chemistry and Biology, Surface Physics and Chemistry. Linköping University, Faculty of Science & Engineering.
    Gao, Feng
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, Faculty of Science & Engineering. Univ Oxford, England.
    Snaith, Henry J.
    Univ Oxford, England.
    Planar perovskite solar cells with long-term stability using ionic liquid additives2019In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 571, no 7764, p. 245-250Article in journal (Refereed)
    Abstract [en]

    Solar cells based on metal halide perovskites are one of the most promising photovoltaic technologies(1-4). Over the past few years, the long-term operational stability of such devices has been greatly improved by tuning the composition of the perovskites(5-9), optimizing the interfaces within the device structures(10-13), and using new encapsulation techniques(14,15). However, further improvements are required in order to deliver a longer-lasting technology. Ion migration in the perovskite active layer-especially under illumination and heat-is arguably the most difficult aspect to mitigate(16-18). Here we incorporate ionic liquids into the perovskite film and thence into positive-intrinsic-negative photovoltaic devices, increasing the device efficiency and markedly improving the long-term device stability. Specifically, we observe a degradation in performance of only around five per cent for the most stable encapsulated device under continuous simulated full-spectrum sunlight for more than 1,800 hours at 70 to 75 degrees Celsius, and estimate that the time required for the device to drop to eighty per cent of its peak performance is about 5,200 hours. Our demonstration of long-term operational, stable solar cells under intense conditions is a key step towards a reliable perovskite photovoltaic technology.

  • 3.
    Berggren, Magnus
    et al.
    Bell Laboratories, Murray Hill, New Jersey, USA.
    Dodabalapur, A.
    Bell Laboratories, Murray Hill, New Jersey, USA.
    Slusher, R. E.
    Bell Laboratories, Murray Hill, New Jersey, USA.
    Bao, Z.
    Bell Laboratories, Murray Hill, New Jersey, USA.
    Light amplification in organic thin films using cascade energy transfer1997In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 389, p. 466-469Article in journal (Refereed)
    Abstract [en]

    There is currently renewed interest in the development of lasers using solid-state organic and polymeric materials as the gain media. These materials have a number of properties that make them good candidates for such applications — for example, emission bands that are displaced (via a Stokes shift) from absorption bands, and the ease with which the emitting species can be embedded in a suitable host material1, 2, 3, 4, 5. But despite these advantages, the threshold power densities required for light amplification that have been reported so far have been high6, 7, 8. Here we describe an approach, based on energy transfer between molecular species, that can lower the threshold for stimulated emission and laser action while improving markedly the waveguiding properties of the active material. In our materials, an initial molecular excited state is generated in the host compound by absorption of light; this state is then resonantly and non-radiatively transferred down in energy (through one or more steps) between suitably matched dye molecules dispersed in the host, so ensuring that the absorption losses at the final emission wavelengths are very small. Such composite gain media provide provide broad tunability of the emission wavelength, and also decouple the optical emission properties from the transport properties, so providing greater flexibility for the design of future electrically driven device structures.

  • 4.
    Berggren, Magnus
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology. null.
    Inganäs, Olle
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology. null.
    Gustafsson, Göran
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology. null.
    Rasmusson, J.
    Chalmers Tekniska Högskola.
    Andersson, Mats R.
    Chalmers Tekniska Högskola.
    Hjertberg, T.
    Chalmers Tekniska Högskola.
    Wennerström, O.
    Chalmers Tekniska Högskola.
    Light-emitting diodes with variable colours from polymer blends1994In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 372, no 6505, p. 444-446Article in journal (Refereed)
    Abstract [en]

    THE range of materials now available for polymer-based light-emitting diodes (LEDs) is such that electroluminescence can be obtained throughout the visible spectrum(1-12). Here we show that, by blending polymers with different emission and charge-transport characteristics, LEDs can be fabricated in which the emission colour varies as a function of the operating voltage. This phenomenon arises from the self-organizing properties of the blends, in which entropy drives phase separation of the constituent polymers and gives rise to submicrometre-sized domains having a range of compositions and emission characteristics. Emission from domains of different composition is controlled by the ease with which charge is injected, which in turn depends on the applied voltage.

  • 5.
    Cardoso-Moreira, Margarida
    et al.
    Heidelberg Univ ZMBH, Germany; Univ Lausanne, Switzerland.
    Halbert, Jean
    Univ Lausanne, Switzerland.
    Valloton, Delphine
    Univ Lausanne, Switzerland.
    Velten, Britta
    European Mol Biol Lab, Germany.
    Chen, Chunyan
    Chinese Acad Sci, Peoples R China; Chinese Acad Sci, Peoples R China; Univ Chinese Acad Sci, Peoples R China.
    Shao, Yi
    Chinese Acad Sci, Peoples R China; Chinese Acad Sci, Peoples R China; Univ Chinese Acad Sci, Peoples R China.
    Liechti, Angelica
    Univ Lausanne, Switzerland.
    Ascencao, Kelly
    Univ Lausanne, Switzerland.
    Rummel, Coralie
    Univ Lausanne, Switzerland.
    Ovchinnikova, Svetlana
    Heidelberg Univ ZMBH, Germany.
    Mazin, Pavel V.
    Skolkovo Inst Sci and Technol, Russia; RAS, Russia; HSE Univ, Russia.
    Xenarios, Ioannis
    Univ Lausanne, Switzerland.
    Harshman, Keith
    Univ Lausanne, Switzerland.
    Mort, Matthew
    Cardiff Univ, Wales.
    Cooper, David N.
    Cardiff Univ, Wales.
    Sandi, Carmen
    Ecole Polytech Fed Lausanne, Switzerland.
    Soares, Michael J.
    Univ Kansas, MO USA; Childrens Mercy, MO USA.
    Ferreira, Paula G.
    Univ Porto, Portugal; Univ Porto, Portugal.
    Afonso, Sandra
    Univ Porto, Portugal.
    Carneiro, Miguel
    Univ Porto, Portugal; Univ Porto, Portugal.
    Turner, James M. A.
    Francis Crick Inst, England.
    VandeBerg, John L.
    Univ Texas Rio Grande Valley, TX USA; Univ Texas Rio Grande Valley, TX USA; Univ Texas Rio Grande Valley, TX USA; Univ Texas Rio Grande Valley, TX USA; Univ Texas Rio Grande Valley, TX USA; Univ Texas Rio Grande Valley, TX USA.
    Fallahshahroudi, Amir
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Behr, Ruediger
    Leibniz Inst Primate Res DPZ, Germany; DZHK German Ctr Cardiovasc Res, Germany.
    Lisgo, Steven
    Newcastle Univ, England.
    Lindsay, Susan
    Newcastle Univ, England.
    Khaitovich, Philipp
    Skolkovo Inst Sci and Technol, Russia; Chinese Acad Sci, Peoples R China; Univ Chinese Acad Sci, Peoples R China.
    Huber, Wolfgang
    European Mol Biol Lab, Germany.
    Baker, Julie
    Stanford Univ, CA 94305 USA.
    Anders, Simon
    Heidelberg Univ ZMBH, Germany.
    Zhang, Yong E.
    Chinese Acad Sci, Peoples R China; Chinese Acad Sci, Peoples R China; Chinese Acad Sci, Peoples R China.
    Kaessmann, Henrik
    Heidelberg Univ ZMBH, Germany.
    Gene expression across mammalian organ development2019In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 571, no 7766, p. 505-+Article in journal (Refereed)
    Abstract [en]

    The evolution of gene expression in mammalian organ development remains largely uncharacterized. Here we report the transcriptomes of seven organs (cerebrum, cerebellum, heart, kidney, liver, ovary and testis) across developmental time points from early organogenesis to adulthood for human, rhesus macaque, mouse, rat, rabbit, opossum and chicken. Comparisons of gene expression patterns identified correspondences of developmental stages across species, and differences in the timing of key events during the development of the gonads. We found that the breadth of gene expression and the extent of purifying selection gradually decrease during development, whereas the amount of positive selection and expression of new genes increase. We identified differences in the temporal trajectories of expression of individual genes across species, with brain tissues showing the smallest percentage of trajectory changes, and the liver and testis showing the largest. Our work provides a resource of developmental transcriptomes of seven organs across seven species, and comparative analyses that characterize the development and evolution of mammalian organs.

  • 6.
    Dong, X.-P.
    et al.
    Department of Molecular, Cellular, and Developmental Biology, University of Michigan, 830 North University, Ann Arbor, MI 48109, United States.
    Cheng, X.
    Department of Molecular, Cellular, and Developmental Biology, University of Michigan, 830 North University, Ann Arbor, MI 48109, United States.
    Mills, E.
    Department of Molecular, Cellular, and Developmental Biology, University of Michigan, 830 North University, Ann Arbor, MI 48109, United States.
    Delling, M.
    Department of Cardiology, Children's Hospital Boston, Enders 1350, 320 Longwood Avenue, Boston, MA 02115, United States.
    Wang, F.
    Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
    Kurz, Tino
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Pharmacology .
    Xu, H.
    Department of Molecular, Cellular, and Developmental Biology, University of Michigan, 830 North University, Ann Arbor, MI 48109, United States.
    The type IV mucolipidosis-associated protein TRPML1 is an endolysosomal iron release channel2008In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 455, no 7215, p. 992-996Article in journal (Refereed)
    Abstract [en]

    TRPML1 (mucolipin 1, also known as MCOLN1) is predicted to be an intracellular late endosomal and lysosomal ion channel protein that belongs to the mucolipin subfamily of transient receptor potential (TRP) proteins. Mutations in the human TRPML1 gene cause mucolipidosis type IV disease (ML4). ML4 patients have motor impairment, mental retardation, retinal degeneration and iron-deficiency anaemia. Because aberrant iron metabolism may cause neural and retinal degeneration, it may be a primary cause of ML4 phenotypes. In most mammalian cells, release of iron from endosomes and lysosomes after iron uptake by endocytosis of Fe3+-bound transferrin receptors, or after lysosomal degradation of ferritin-iron complexes and autophagic ingestion of iron-containing macromolecules, is the chief source of cellular iron. The divalent metal transporter protein DMT1 (also known as SLC11A2) is the only endosomal Fe2+ transporter known at present and it is highly expressed in erythroid precursors. Genetic studies, however, suggest the existence of a DMT1-independent endosomal and lysosomal Fe2+ transport protein. By measuring radiolabelled iron uptake, by monitoring the levels of cytosolic and intralysosomal iron and by directly patch-clamping the late endosomal and lysosomal membrane, here we show that TRPML1 functions as a Fe2+ permeable channel in late endosomes and lysosomes. ML4 mutations are shown to impair the ability of TRPML1 to permeate Fe2+ at varying degrees, which correlate well with the disease severity. A comparison of TRPML1-/-ML4 and control human skin fibroblasts showed a reduction in cytosolic Fe2+ levels, an increase in intralysosomal Fe 2+ levels and an accumulation of lipofuscin-like molecules in TRPML1-/- cells. We propose that TRPML1 mediates a mechanism by which Fe2+ is released from late endosomes and lysosomes. Our results indicate that impaired iron transport may contribute to both haematological and degenerative symptoms of ML4 patients. ©2008 Macmillan Publishers Limited. All rights reserved.

  • 7.
    Dubrovinsky, L.
    et al.
    University of Bayreuth, Germany.
    Dubrovinskaia, N.
    University of Bayreuth, Germany.
    Bykova, E.
    University of Bayreuth, Germany; University of Bayreuth, Germany.
    Bykov, M.
    University of Bayreuth, Germany.
    Prakapenka, V.
    University of Chicago, IL 60437 USA.
    Prescher, C.
    University of Chicago, IL 60437 USA.
    Glazyrin, K.
    Deutsch Elektronen Synchrotron DESY, Germany.
    Liermann, H. -P.
    Deutsch Elektronen Synchrotron DESY, Germany.
    Hanfland, M.
    European Synchrotron Radiat Facil, France.
    Ekholm, Marcus
    Linköping University, Department of Physics, Chemistry and Biology, Theoretical Physics. Linköping University, Faculty of Science & Engineering.
    Feng, Qingguo
    Linköping University, Department of Physics, Chemistry and Biology, Theoretical Physics. Linköping University, The Institute of Technology.
    Pourovskii, L. V.
    Linköping University, Faculty of Science & Engineering. Ecole Polytech, France.
    Katsnelson, M. I.
    Radboud University of Nijmegen, Netherlands; Ural Federal University, Russia.
    Wills, J. M.
    Los Alamos National Lab, NM 87545 USA.
    Abrikosov, Igor
    Linköping University, Department of Physics, Chemistry and Biology, Theoretical Physics. Linköping University, Faculty of Science & Engineering. National University of Science and Technology MISIS, Russia.
    The most incompressible metal osmium at static pressures above 750 gigapascals2015In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 525, no 7568, p. 226-+Article in journal (Refereed)
    Abstract [en]

    Metallic osmium (Os) is one of the most exceptional elemental materials, having, at ambient pressure, the highest known density and one of the highest cohesive energies and melting temperatures(1). It is also very incompressible(2-4), but its high-pressure behaviour is not well understood because it has been studied(2-6) so far only at pressures below 75 gigapascals. Here we report powder X-ray diffraction measurements on Os at multi-megabar pressures using both conventional and double-stage diamond anvil cells(7), with accurate pressure determination ensured by first obtaining self-consistent equations of state of gold, platinum, and tungsten in static experiments up to 500 gigapascals. These measurements allow us to show that Os retains its hexagonal close-packed structure upon compression to over 770 gigapascals. But although its molar volume monotonically decreases with pressure, the unit cell parameter ratio of Os exhibits anomalies at approximately 150 gigapascals and 440 gigapascals. Dynamical mean-field theory calculations suggest that the former anomaly is a signature of the topological change of the Fermi surface for valence electrons. However, the anomaly at 440 gigapascals might be related to an electronic transition associated with pressure-induced interactions between core electrons. The ability to affect the core electrons under static high-pressure experimental conditions, even for incompressible metals such as Os, opens up opportunities to search for new states of matter under extreme compression.

  • 8.
    Ek, Monica
    et al.
    Department of Medicine, Unit of Rheumatology, The Karolinska Institute, Stockholm, Sweden.
    Engblom, David
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Saha, Sipra
    Department of Medical Biochemistry and Biophysics, The Karolinska Institute, Stockholm, Sweden.
    Blomqvist, Anders
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Jakobsson, Per-Johan
    Department of Medical Biochemistry and Biophysics, The Karolinska Institute, Stockholm, Sweden.
    Ericsson-Dahlstrand, Anders
    Department of Medicine, Unit of Rheumatology, The Karolinska Institute, Stockholm, Sweden.
    Inflammatory response: pathway across the blood–brain barrier2001In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 410, p. 430-431Article in journal (Refereed)
    Abstract [en]

    No abstract available.

  • 9.
    Gad, Helge
    et al.
    Karolinska Institute, Sweden .
    Koolmeister, Tobias
    Karolinska Institute, Sweden .
    Jemth, Ann-Sofie
    Karolinska Institute, Sweden .
    Eshtad, Saeed
    Karolinska Institute, Sweden .
    Jacques, Sylvain A.
    Karolinska Institute, Sweden .
    Ström, Cecilia E.
    Karolinska Institute, Sweden .
    Svensson, Linda M.
    Stockholm University, Sweden .
    Schultz, Niklas
    Karolinska Institute, Sweden .
    Lundbäck, Thomas
    Karolinska Institute, Sweden .
    Osk Einarsdottir, Berglind
    University of Gothenburg, Sweden; Sahlgrenska University Hospital, Sweden .
    Saleh, Aljona
    Stockholm University, Sweden .
    Göktürk, Camilla
    Karolinska Institute, Sweden .
    Baranczewski, Pawel
    Karolinska Institute, Sweden Uppsala University, Sweden .
    Svensson, Richard
    Karolinska Institute, Sweden; Uppsala University, Sweden .
    Berntsson, Ronnie P. -A.
    Stockholm University, Sweden .
    Gustafsson, Robert
    Stockholm University, Sweden .
    Strömberg, Kia
    Karolinska Institute, Sweden .
    Sanjiv, Kumar
    Karolinska Institute, Sweden .
    Jacques-Cordonnier, Marie-Caroline
    Karolinska Institute, Sweden .
    Desroses, Matthieu
    Karolinska Institute, Sweden .
    Gustavsson, Anna-Lena
    Karolinska Institute, Sweden .
    Olofsson, Roger
    University of Gothenburg, Sweden; Sahlgrenska University Hospital, Sweden .
    Johansson, Fredrik
    Stockholm University, Sweden .
    Homan, Evert J.
    Karolinska Institute, Sweden .
    Loseva, Olga
    Karolinska Institute, Sweden .
    Bräutigam, Lars
    Karolinska Institute, Sweden .
    Johansson, Lars
    Karolinska Institute, Sweden .
    Höglund, Andreas
    Karolinska Institute, Sweden .
    Hagenkort, Anna
    Karolinska Institute, Sweden .
    Pham, Therese
    Karolinska Institute, Sweden .
    Altun, Mikael
    Karolinska Institute, Sweden .
    Gaugaz, Fabienne Z.
    Karolinska Institute, Sweden; Uppsala University, Sweden .
    Vikingsson, Svante
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Evers, Bastiaan
    Karolinska Institute, Sweden .
    Henriksson, Martin
    Karolinska Institute, Sweden .
    Vallin, Karl S. A.
    Karolinska Institute, Sweden .
    Wallner, Olov A.
    Karolinska Institute, Sweden .
    Hammarström, Lars G. J.
    Karolinska Institute, Sweden .
    Wiita, Elisee
    Karolinska Institute, Sweden .
    Almlöf, Ingrid
    Karolinska Institute, Sweden .
    Kalderén, Christina
    Karolinska Institute, Sweden .
    Axelsson, Hanna
    Karolinska Institute, Sweden .
    Djureinovic, Tatjana
    Stockholm University, Sweden .
    Carreras Puigvert, Jordi
    Karolinska Institute, Sweden .
    Häggblad, Maria
    Stockholm University, Sweden .
    Jeppsson, Fredrik
    Karolinska Institute, Sweden .
    Martens, Ulf
    Stockholm University, Sweden .
    Lundin, Cecilia
    Karolinska Institute, Sweden .
    Lundgren, Bo
    Stockholm University, Sweden .
    Granelli, Ingrid
    Stockholm University, Sweden .
    Jenmalm Jensen, Annika
    Karolinska Institute, Sweden .
    Artursson, Per
    Karolinska Institute, Sweden; Uppsala University, Sweden .
    Nilsson, Jonas A.
    University of Gothenburg, Sweden, Sahlgrens University Hospital, Sweden .
    Stenmark, Pål
    Stockholm University, Sweden .
    Scobie, Martin
    Karolinska Institute, Sweden .
    Warpman Berglund, Ulrika
    Karolinska Institute, Sweden .
    Helleday, Thomas
    Karolinska Institute, Sweden .
    MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool2014In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 508, no 7495, p. 215-221Article in journal (Refereed)
    Abstract [en]

    Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.

  • 10.
    Gudasz, Cristian
    et al.
    Limnology, Department of Ecology and Evolution, Uppsala University.
    Bastviken, David
    Linköping University, The Tema Institute, Department of Water and Environmental Studies. Linköping University, Faculty of Arts and Sciences.
    Steger, Kristin
    Limnology, Department of Ecology and Evolution, Uppsala University.
    Premke, Katrin
    Limnology, Department of Ecology and Evolution, Uppsala University.
    Sobek, Sebastian
    Limnology, Department of Ecology and Evolution, Uppsala University.
    Tranvik, Lars J.
    Limnology, Department of Ecology and Evolution, Uppsala University.
    Temperature-controlled organic carbon mineralization in lake sediments2010In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 466, no 7305, p. 478-481Article in journal (Other academic)
    Abstract [en]

    Peatlands, soils and the ocean floor are well-recognized as sites of organic carbon accumulation and represent important global carbon sinks. Although the annual burial of organic carbon in lakes and reservoirs exceeds that of ocean sediments, these inland waters are components of the global carbon cycle that receive only limited attention. Of the organic carbon that is being deposited onto the sediments, a certain proportion will be mineralized and the remainder will be buried over geological timescales. Here we assess the relationship between sediment organic carbon mineralization and temperature in a cross-system survey of boreal lakes in Sweden, and with input from a compilation of published data from a wide range of lakes that differ with respect to climate, productivity and organic carbon source. We find that the mineralization of organic carbon in lake sediments exhibits a strongly positive relationship with temperature, which suggests that warmer water temperatures lead to more mineralization and less organic carbon burial. Assuming that future organic carbon delivery to the lake sediments will be similar to that under present-day conditions, we estimate that temperature increases following the latest scenarios presented by the Intergovernmental Panel on Climate Change could result in a 4-27 per cent (0.9-6.4 Tg C yr(-1)) decrease in annual organic carbon burial in boreal lakes.

  • 11.
    Heinzel, T.
    et al.
    University of California, San Diego, USA.
    Lavinsky, R. M.
    University of California, San Diego, USA.
    Mullen, T. M.
    University of California, San Diego, USA.
    Söderström, Mats
    University of California, San Diego, USA.
    Laherty, C. D.
    Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
    Torchia, J.
    University of California, San Diego, USA.
    Yang, W. M.
    University of South Florida, Tampa, USA.
    Brard, G.
    University of California, San Diego, USA.
    Ngo, S. D.
    University of California, San Diego, USA.
    Davie, J. R.
    University of Manitoba, Winnipeg, Canada.
    Seto, E.
    University of South Florida, Tampa, USA.
    Eisenman, R. N.
    Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
    Rose, D. W.
    University of California, San Diego, USA.
    Glass, C. K.
    University of California, San Diego, USA.
    Rosenfeld, M. G.
    University of California, San Diego, USA.
    A complex containing N-CoR, mSin3 and histone deacetylase mediates transcriptional repression1997In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 387, no 6628, p. 43-48Article in journal (Refereed)
    Abstract [en]

    Transcriptional repression by nuclear receptors has been correlated to binding of the putative co-repressor, N-CoR. A complex has been identified that contains N-CoR, the Mad presumptive co-repressor mSin3, and the histone deacetylase mRPD3, and which is required for both nuclear receptor- and Mad-dependent repression, but not for repression by transcription factors of the ets-domain family. These data predict that the ligand-induced switch of heterodimeric nuclear receptors from repressor to activator functions involves the exchange of complexes containing histone deacetylases with those that have histone acetylase activity.

  • 12.
    Hoshino, Ayuko
    et al.
    Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA.
    Costa-Silva, Bruno
    Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA.
    Shen, Tang-Long
    Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA; National Taiwan University, Taiwan; National Taiwan University, Taiwan.
    Rodrigues, Goncalo
    Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA; University of Porto, Portugal.
    Hashimoto, Ayako
    Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA; University of Tokyo, Japan.
    Tesic Mark, Milica
    Rockefeller University, NY 10065 USA.
    Molina, Henrik
    Rockefeller University, NY 10065 USA.
    Kohsaka, Shinji
    Mem Sloan Kettering Cancer Centre, NY 10065 USA.
    Di Giannatale, Angela
    Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA.
    Ceder, Sophia
    Karolinska Institute, Sweden.
    Singh, Swarnima
    Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA.
    Williams, Caitlin
    Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA.
    Soplop, Nadine
    Rockefeller University, NY 10065 USA.
    Uryu, Kunihiro
    Rockefeller University, NY 10065 USA.
    Pharmer, Lindsay
    Mem Sloan Kettering Cancer Centre, NY 10065 USA.
    King, Tari
    Mem Sloan Kettering Cancer Centre, NY 10065 USA.
    Bojmar, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA.
    Davies, Alexander E.
    University of Calif Berkeley, CA 94720 USA.
    Ararso, Yonathan
    Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA.
    Zhang, Tuo
    Weill Cornell Med, NY 10021 USA.
    Zhang, Haiying
    Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA.
    Hernandez, Jonathan
    Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA; Mem Sloan Kettering Cancer Centre, NY 10065 USA.
    Weiss, Joshua M.
    Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA.
    Dumont-Cole, Vanessa D.
    Mem Sloan Kettering Cancer Centre, NY 10065 USA.
    Kramer, Kimberly
    Mem Sloan Kettering Cancer Centre, NY 10065 USA.
    Wexler, Leonard H.
    Mem Sloan Kettering Cancer Centre, NY 10065 USA.
    Narendran, Aru
    Alberta Childrens Prov Gen Hospital, Canada.
    Schwartz, Gary K.
    Columbia University, NY 10032 USA.
    Healey, John H.
    Mem Sloan Kettering Cancer Centre, NY 10065 USA.
    Sandström, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Jorgen Labori, Knut
    Oslo University Hospital, Norway.
    Kure, Elin H.
    Oslo University Hospital, Norway.
    Grandgenett, Paul M.
    University of Nebraska Medical Centre, NE 68198 USA.
    Hollingsworth, Michael A.
    University of Nebraska Medical Centre, NE 68198 USA.
    de Sousa, Maria
    Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA; University of Porto, Portugal.
    Kaur, Sukhwinder
    University of Nebraska Medical Centre, NE 68198 USA.
    Jain, Maneesh
    University of Nebraska Medical Centre, NE 68198 USA.
    Mallya, Kavita
    University of Nebraska Medical Centre, NE 68198 USA.
    Batra, Surinder K.
    University of Nebraska Medical Centre, NE 68198 USA.
    Jarnagin, William R.
    Mem Sloan Kettering Cancer Centre, NY 10065 USA.
    Brady, Mary S.
    Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA; Mem Sloan Kettering Cancer Centre, NY 10065 USA.
    Fodstad, Oystein
    Oslo University Hospital, Norway; University of Oslo, Norway.
    Muller, Volkmar
    University of Medical Centre, Germany.
    Pantel, Klaus
    University of Medical Centre Hamburg Eppendorf, Germany.
    Minn, Andy J.
    University of Penn, PA 19104 USA.
    Bissell, Mina J.
    University of Calif Berkeley, CA 94720 USA.
    Garcia, Benjamin A.
    University of Penn, PA 19104 USA.
    Kang, Yibin
    Princeton University, NJ 08544 USA; Rutgers Cancer Institute New Jersey, NJ 08903 USA.
    Rajasekhar, Vinagolu K.
    Mem Sloan Kettering Cancer Centre, NY 10065 USA.
    Ghajar, Cyrus M.
    Fred Hutchinson Cancer Research Centre, WA 98109 USA.
    Matei, Irina
    Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA.
    Peinado, Hector
    Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA; Spanish National Cancer Research Centre CNIO, Spain.
    Bromberg, Jacqueline
    Mem Sloan Kettering Cancer Centre, NY 10065 USA; Weill Cornell Med, NY 10021 USA.
    Lyden, David
    Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA; Mem Sloan Kettering Cancer Centre, NY 10065 USA.
    Tumour exosome integrins determine organotropic metastasis2015In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 527, no 7578, p. 329-+Article in journal (Refereed)
    Abstract [en]

    Ever since Stephen Pagets 1889 hypothesis, metastatic organotropism has remained one of cancers greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver-and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins alpha(6)beta(4) and alpha(6)beta(1) were associated with lung metastasis, while exosomal integrin alpha(v)beta(5) was linked to liver metastasis. Targeting the integrins alpha(6)beta(4) and alpha(v)beta(5) decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis.

  • 13. Hugot, J-P
    et al.
    Chamaillard, M
    Zouali, H
    Lesage, S
    C´zard, J-P
    Belaiche, J
    Almer, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, GE: gastromed.
    Tysk, C
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology.
    O'Morain, A
    Gassull, M
    Binder, V
    Finkel, Y
    Cortot, A
    Modigliani, R
    Laurent-Puig, P
    Gower-Rousseau, C
    Macry, J
    Comombel, J-F
    Sahbatou, M
    Thomas, G
    Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease2001In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 411, no 6837, p. 599-603Article in journal (Refereed)
    Abstract [en]

    Crohn's disease and ulcerative colitis, the two main types of chronic inflammatory bowel disease, are multifactorial conditions of unknown aetiology. A susceptibility locus for Crohn's disease has been mapped to chromosome 16. Here we have used a positional-cloning strategy, based on linkage analysis followed by linkage disequilibrium mapping, to identify three independent associations for Crohn's disease: a frameshift variant and two missense variants of NOD2, encoding a member of the Apaf-1/Ced-4 superfamily of apoptosis regulators that is expressed in monocytes. These NOD2 variants alter the structure of either the leucine-rich repeat domain of the protein or the adjacent region. NOD2 activates nuclear factor NF-?B, this activating function is regulated by the carboxy-terminal leucine-rich repeat domain, which has an inhibitory role and also acts as an intracellular receptor for components of microbial pathogens. These observations suggest that the NOD2 gene product confers susceptibility to Crohn's disease by altering the recognition of these components and/or by over-activating NF-?B in monocytes, thus documenting a molecular model for the pathogenic mechanism of Crohn's disease that can now be further investigated.

  • 14.
    Hörlein, A. J.
    et al.
    University of California, San Diego, USA.
    Näär, A. M.
    University of California, San Diego, USA.
    Heinzel, T.
    University of California, San Diego, USA.
    Torchia, J.
    University of California, San Diego, USA.
    Gloss, B.
    University of California, San Diego, USA.
    Kurokawa, R.
    University of California, San Diego, USA.
    Ryan, A.
    University of California, San Diego, USA.
    Kamei, Y.
    University of California, San Diego, USA.
    Söderström, Mats
    University of California, San Diego, USA.
    Glass, C. K.
    University of California, San Diego, USA.
    Rosenfeld, M. G.
    University of California, San Diego, USA.
    Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressor1995In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 377, no 6548, p. 397-404Article in journal (Refereed)
    Abstract [en]

    Thyroid-hormone and retinoic-acid receptors exert their regulatory functions by acting as both activators and repressors of gene expression. A nuclear receptor co-repressor (N-CoR) of relative molecular mass 270K has been identified which mediates ligand-independent inhibition of gene transcription by these receptors, suggesting that the molecular mechanisms of repression by thyroid-hormone and retinoic-acid receptors are analogous to the co-repressor-dependent transcriptional inhibitory mechanisms of yeast and Drosophila.

  • 15.
    Keeling, L.
    et al.
    Dept. of Anim. Environ. and Health, Swed. Univ. of Agricultural Sciences, PO Box 234, 53223 Skara, Sweden.
    Andersson, L.
    Dept. Med. Biochem. and Microbiol., Uppsala University, Box 597, 75124 Uppsala, Sweden, Dept. of Anim. Breeding and Genetics, Swed. Univ. of Agricultural Sciences, 75124 Uppsala, Sweden.
    Schutz, K.E.
    Schütz, K.E., Dept. of Anim. Environ. and Health, Swed. Univ. of Agricultural Sciences, PO Box 234, 53223 Skara, Sweden, AgResearch, Animal Behaviour and Welfare, Private Bag 3123, Hamilton, New Zealand.
    Kerje, Susanne
    Linköping University, Department of Physics, Chemistry and Biology, Zoology .
    Fredriksson, R.
    Dept. of Anim. Breeding and Genetics, Swed. Univ. of Agricultural Sciences, 75124 Uppsala, Sweden.
    Carlborg, O.
    Carlborg, Ö., Dept. of Anim. Breeding and Genetics, Swed. Univ. of Agricultural Sciences, 75124 Uppsala, Sweden, Roslin Institute, Roslin, Midlothian EH25 9PS, United Kingdom.
    Cornwallis, C.K.
    Dept. of Animal and Plant Sciences, University of Sheffield, Sheffield S10 2TN, United Kingdom.
    Pizzari, Tom
    Linköping University, Department of Physics, Chemistry and Biology, Zoology .
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Zoology .
    Feather pecking and victim pigmentation2004In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 431, no 7009, p. 645-646Article in journal (Refereed)
    Abstract [en]

    [No abstract available]

  • 16.
    Kurokawa, R.
    et al.
    University of California, San Diego, USA.
    Söderström, Mats
    University of California, San Diego, USA.
    Hörlein, A.
    University of California, San Diego, USA.
    Halachmi, S.
    Dana Farber Cancer Institute, Boston, Massachusetts, USA .
    Brown, M.
    Dana Farber Cancer Institute, Boston, Massachusetts, USA .
    Rosenfeld, M. G.
    University of California, San Diego, USA.
    Glass, C. K.
    University of California, San Diego, USA.
    Polarity-specific activities of retinoic acid receptors determined by a co-repressor.1995In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 377, no 6548, p. 451-454Article in journal (Refereed)
    Abstract [en]

    Retinoic acid receptors (RARs) and retinoid-X receptors (RXRs) activate or repress transcription by binding as heterodimers to DNA-response elements that generally consist of two direct repeat half-sites of consensus sequence AGGTCA. On response elements consisting of direct repeats spaced by five base pairs (DR + 5 elements), RAR/RXR heterodimers activate transcription in response to RAR-specific ligands, such as all-trans-retinoic acid (RA). In contrast, on elements consisting of direct repeats spaced by one base pair (DR + 1 elements), RAR/RXR heterodimers exhibit little or no response to activating ligands and repress RXR-dependent transcription. Here we show that ligand-dependent transactivation by RAR on DR + 5 elements requires the dissociation of a new nuclear receptor co-repressor, N-CoR, and recruitment of the putative co-activators p140 and p160. Surprisingly, on DR + 1 elements, N-CoR remains associated with RAR/RXR heterodimers even in the presence of RAR ligands, resulting in constitutive repression. These observations indicate that DNA-response elements can allosterically regulate RAR-co-repressor interactions to determine positive or negative regulation of gene expression.

  • 17.
    Los, Marek Jan
    et al.
    Institute of Biochemistry, Albert-Ludwigs-University, Hermann-Heder-Strasse 7, D79104 Freiburg im Breisgau, Germany.
    Vandecraen, M.
    Laboratory of Molecular Biology, University of Ghent, Ghent, Belgium.
    Penning, Lc
    Laboratory of Molecular Biology, University of Ghent, Ghent, Belgium.
    Schenk, H.
    Divisions of Immunochemistry § Divisions of Immunogenetics, Tumorimmunology Program, German Cancer Research Center, Heidelberg, Germany.
    Westendorp, M.
    Divisions of Immunochemistry § Divisions of Immunogenetics, Tumorimmunology Program, German Cancer Research Center, Heidelberg, Germany.
    Baeuerle, Pa
    Institute of Biochemistry, Albert-Ludwigs-University, Hermann-Heder-Strasse 7, D79104 Freiburg im Breisgau, Germany.
    Droge, W.
    Divisions of Immunochemistry § Divisions of Immunogenetics, Tumorimmunology Program, German Cancer Research Center, Heidelberg, Germany.
    Krammer, Peter
    Divisions of Immunochemistry § Divisions of Immunogenetics, Tumorimmunology Program, German Cancer Research Center, Heidelberg, Germany.
    Fiers, W.
    Laboratory of Molecular Biology, University of Ghent, Ghent, Belgium.
    Schulze-Osthoff, Klaus
    Institute of Biochemistry, Albert-Ludwigs-University, Hermann-Heder-Strasse 7, D79104 Freiburg im Breisgau, Germany.
    Requirement of an Ice/Ced-3 Protease for Fas/Apo-1-Mediated Apoptosis1995In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 375, no 6526, p. 81-83Article in journal (Refereed)
    Abstract [en]

    THE Fas/APO-1 receptor is one of the major regulators of apoptosis(1-7). We report here that Fas/APO-1-mediated apoptosis requires the activation of a new class of cysteine proteases, including interleukin-1 beta-converting enzyme (ICE)(8-10) which are homologous to the product of the Caenorhabditis elegans cell-death gene ced-3 (refs 11, 12). Triggering of Fas/APO-1 rapidly stimulated the proteolytic activity of ICE. Overexpression of ICE, achieved by electroporation and microinjection, strongly potentiated Fas/APO-1-mediated cell death. In addition, inhibition of ICE activity by protease inhibitors, as well as by transient expression of the pox virus-derived serpin inhibitor CrmA or an antisense ICE construct, substantially suppressed Fas/APO-1-triggered cell death. We conclude that activation of ICE or an ICE-related protease is a critical event in Fas/APO-1-mediated cell death.

  • 18.
    Lundström, Ingemar
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Applied Physics .
    Artificial noses: Picture the smell2000In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 406, no 6797, p. 682-683Article, review/survey (Refereed)
    Abstract [en]

    [No abstract available]

  • 19.
    Lundström, Ingemar
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology.
    Erlandsson, Ragnar
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology.
    Frykman, Ulf
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology.
    Hedborg, Eva
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology.
    Spetz, Anita
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology.
    Sundgren, Hans
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology.
    Welin, Stefan
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology.
    Winquist, Fredrik
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology.
    Artificial 'olfactory' images from a chemical sensor using a light-pulse technique1991In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 352, no 6330, p. 47-50Article in journal (Refereed)
    Abstract [en]

    THERE is much interest in the use of chemical sensor arrays, in conjunction with pattern-recognition routines, for developing artificial olfactory devices-electronic noses-which can characterize the chemical composition of gas mixtures 1-5. Here we describe a technique that uses a continuous sensing surface and a detection method involving a scanning pulsed light source, to generate images that represent a fingerprint of the gases detected. The detector is a large-area field-effect device with a number of different catalytic metals constituting the detecting surface (the devices active gate) 6,7. A pulsed light beam scanned across this surface generates a photocapacitive current that varies with the value of the surface potential 8,9. A continuous sensing surface of this type provides information that would require an array of hundreds of discrete sensors. The technique also provides a new means of studying the coupling between the electronic properties of catalytic metals and chemical reactions taking place on their surfaces.

  • 20. Marteyn, Benoit
    et al.
    West, Nicholas P.
    Browning, Douglas F.
    Cole, Jeffery A.
    Shaw, Jonathan G.
    Palm, Fredrik
    Uppsala universitet, Institutionen för medicinsk cellbiologi.
    Mounier, Joelle
    Prevost, Marie-Christine
    Sansonetti, Philippe
    Tang, Christoph M.
    Modulation of Shigella virulence in response to available oxygen in vivo2010In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 465, no 7296, p. 355-358Article in journal (Refereed)
    Abstract [en]

    Bacteria coordinate expression of virulence determinants in response to localized microenvironments in their hosts. Here we show that Shigella flexneri, which causes dysentery, encounters varying oxygen concentrations in the gastrointestinal tract, which govern activity of its type three secretion system (T3SS). The T3SS is essential for cell invasion and virulence(1). In anaerobic environments (for example, the gastrointestinal tract lumen), Shigella is primed for invasion and expresses extended T3SS needles while reducing Ipa (invasion plasmid antigen) effector secretion. This is mediated by FNR (fumarate and nitrate reduction), a regulator of anaerobic metabolism that represses transcription of spa32 and spa33, virulence genes that regulate secretion through the T3SS. We demonstrate there is a zone of relative oxygenation adjacent to the gastrointestinal tract mucosa, caused by diffusion from the capillary network at the tips of villi. This would reverse the anaerobic block of Ipa secretion, allowing T3SS activation at its precise site of action, enhancing invasion and virulence.

  • 21.
    Mirman, Zachary
    et al.
    Laboratory for Cell Biology and Genetics, Rockefeller University, New York, NY, USA..
    Lottersberger, Francisca
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Laboratory for Cell Biology and Genetics, Rockefeller University, New York, NY, USA..
    Takai, Hiroyuki
    Laboratory for Cell Biology and Genetics, Rockefeller University, New York, NY, USA..
    Kibe, Tatsuya
    Laboratory for Cell Biology and Genetics, Rockefeller University, New York, NY, USA..
    Gong, Yi
    Laboratory for Cell Biology and Genetics, Rockefeller University, New York, NY, USA..
    Takai, Kaori
    Laboratory for Cell Biology and Genetics, Rockefeller University, New York, NY, USA..
    Bianchi, Alessandro
    Laboratory for Cell Biology and Genetics, Rockefeller University, New York, NY, USA.; Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Brighton, UK..
    Zimmermann, Michal
    Laboratory for Cell Biology and Genetics, Rockefeller University, New York, NY, USA.; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada..
    Durocher, Daniel
    Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada..
    de Lange, Titia
    Laboratory for Cell Biology and Genetics, Rockefeller University, New York, NY, USA. delange@rockefeller.edu..
    53BP1-RIF1-shieldin counteracts DSB resection through CST- and Polα-dependent fill-in.2018In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 560, no 7716, p. 112-116Article in journal (Refereed)
    Abstract [en]

    In DNA repair, the resection of double-strand breaks dictates the choice between homology-directed repair-which requires a 3' overhang-and classical non-homologous end joining, which can join unresected ends1,2. BRCA1-mutant cancers show minimal resection of double-strand breaks, which renders them deficient in homology-directed repair and sensitive to inhibitors of poly(ADP-ribose) polymerase 1 (PARP1)3-8. When BRCA1 is absent, the resection of double-strand breaks is thought to be prevented by 53BP1, RIF1 and the REV7-SHLD1-SHLD2-SHLD3 (shieldin) complex, and loss of these factors diminishes sensitivity to PARP1 inhibitors4,6-9. Here we address the mechanism by which 53BP1-RIF1-shieldin regulates the generation of recombinogenic 3' overhangs. We report that CTC1-STN1-TEN1 (CST)10, a complex similar to replication protein A that functions as an accessory factor of polymerase-α (Polα)-primase11, is a downstream effector in the 53BP1 pathway. CST interacts with shieldin and localizes with Polα to sites of DNA damage in a 53BP1- and shieldin-dependent manner. As with loss of 53BP1, RIF1 or shieldin, the depletion of CST leads to increased resection. In BRCA1-deficient cells, CST blocks RAD51 loading and promotes the efficacy of PARP1 inhibitors. In addition, Polα inhibition diminishes the effect of PARP1 inhibitors. These data suggest that CST-Polα-mediated fill-in helps to control the repair of double-strand breaks by 53BP1, RIF1 and shieldin.

  • 22.
    Pace, Michael L.
    et al.
    Institute of Ecosystem Studies, Millbrook, New York, USA.
    Cole, Jonathan J.
    Institute of Ecosystem Studies, Millbrook, New York, USA.
    Carpenter, Stephen R.
    Center for Limnology, University of Wisconsin, Madison, Wisconsin, USA.
    Kitchell, James F.
    Center for Limnology, University of Wisconsin, Madison, Wisconsin, USA.
    Hodgson, James R.
    Department of Biology, St. Norbert College, De Pere, Wisconsin, USA.
    Van de Bogert, Matthew C.
    Institute of Ecosystem Studies, Millbrook, New York, USA.
    Bade, Darren L.
    Center for Limnology, University of Wisconsin, Madison, Wisconsin, USA.
    Kritzberg, Emma S.
    Department of Ecology/Limnology, Lund University, Lund, Sweden.
    Bastviken, David
    Linköping University, Department of Thematic Studies, Department of Water and Environmental Studies. Linköping University, Faculty of Arts and Sciences.
    Whole-lake carbon-13 additions reveal terrestrial support of aquatic food webs2004In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 427, no 6971, p. 240-243Article in journal (Refereed)
    Abstract [en]

    Ecosystems are supported by organic carbon from two distinct sources. Endogenous carbon is produced by photosynthesis within an ecosystem by autotrophic organisms. Exogenous carbon is produced elsewhere and transported into ecosystems. Consumers may use exogenous carbon with consequent influences on population dynamics, predator-prey relationships and ecosystem processes(1). For example, exogenous inputs provide resources that may enhance consumer abundance beyond levels supported by within-system primary production(2). Exogenous fluxes of organic carbon to ecosystems are often large, but this material is recalcitrant and difficult to assimilate, in contrast to endogenously produced organic matter, which is used more easily(3,4). Here we show, by the experimental manipulation of dissolved inorganic C-13 in two lakes, that internal primary production is insufficient to support the food webs of these ecosystems. Additions of NaH (CO3)-C-13 enriched the C-13 content of dissolved inorganic carbon, particulate organic carbon, zooplankton and fish. Dynamics of C-13 indicate that 40-55% of particulate organic carbon and 22-50% of zooplankton carbon are derived from terrestrial sources, showing that there is significant subsidy of these ecosystems by organic carbon produced outside their boundaries.

  • 23.
    Pangala, Sunitha R.
    et al.
    Open University, England; University of Lancaster, England.
    Enrich Prast, Alex
    Linköping University, Department of Thematic Studies, Tema Environmental Change. Linköping University, Faculty of Arts and Sciences. University of Federal Rio de Janeiro, Brazil.
    Basso, Luana S.
    IPEN, Brazil.
    Bittencourt Peixoto, Roberta
    University of Federal Rio de Janeiro, Brazil.
    Bastviken, David
    Linköping University, Department of Thematic Studies, Tema Environmental Change. Linköping University, Faculty of Arts and Sciences.
    Hornibrook, Edward R. C.
    University of Bristol, England; University of British Columbia, Canada.
    Gatti, Luciana V.
    IPEN, Brazil; National Institute Space Research INPE, Brazil.
    Marotta, Humberto
    University of Federal Fluminense, Brazil.
    Silva Braucks Calazans, Luana
    University of Federal Rio de Janeiro, Brazil.
    Monica Sakuragui, Cassia
    University of Federal Rio de Janeiro, Brazil.
    Rodrigues Bastos, Wanderley
    Federal University of Rondonia, Brazil.
    Malm, Olaf
    University of Federal Rio de Janeiro, Brazil.
    Gloor, Emanuel
    University of Leeds, England.
    Bharat Miller, John
    NOAA, CO 80305 USA.
    Gauci, Vincent
    Open University, England.
    Large emissions from floodplain trees close the Amazon methane budget2017In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 552, no 7684, p. 230-+Article in journal (Refereed)
    Abstract [en]

    Wetlands are the largest global source of atmospheric methane (CH4)(1), a potent greenhouse gas. However, methane emission inventories from the Amazon floodplain(2,3), the largest natural geographic source of CH4 in the tropics, consistently underestimate the atmospheric burden of CH4 determined via remote sensing and inversion modelling(4,5), pointing to a major gap in our understanding of the contribution of these ecosystems to CH4 emissions. Here we report CH4 fluxes from the stems of 2,357 individual Amazonian floodplain trees from 13 locations across the central Amazon basin. We find that escape of soil gas through wetland trees is the dominant source of regional CH4 emissions. Methane fluxes from Amazon tree stems were up to 200 times larger than emissions reported for temperate wet forests(6) and tropical peat swamp forests(7), representing the largest non-ebullitive wetland fluxes observed. Emissions from trees had an average stable carbon isotope value (delta C-13) of -66.2 +/- 6.4 per mil, consistent with a soil biogenic origin. We estimate that floodplain trees emit 15.1 +/- 1.8 to 21.2 +/- 2.5 teragrams of CH4 a year, in addition to the 20.5 +/- 5.3 teragrams a year emitted regionally from other sources. Furthermore, we provide a topdown regional estimate of CH4 emissions of 42.7 +/- 5.6 teragrams of CH4 a year for the Amazon basin, based on regular vertical lower-troposphere CH4 profiles covering the period 2010-2013. We find close agreement between our top-down and combined bottom-up estimates, indicating that large CH4 emissions from trees adapted to permanent or seasonal inundation can account for the emission source that is required to close the Amazon CH4 budget. Our findings demonstrate the importance of tree stem surfaces in mediating approximately half of all wetland CH4 emissions in the Amazon floodplain, a region that represents up to one-third of the global wetland CH4 source when trees are combined with other emission sources.

  • 24.
    Persson, A.
    et al.
    Linköping University Hospital, Sweden.
    Paterlini, M.
    Paterlini, M..
    Q&A: An insider's view of the body2008In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 455, no 7216, p. 1036Other (Other academic)
    Abstract [en]

    [No abstract available]

  • 25.
    Pizzari, Tommaso
    et al.
    Swedish University of Agricultural Sciences, Skara, Sweden.
    Cornwallis, Charles K.
    University of Sheffield, UK.
    Løvlie, Hanne
    Stockholm University, Sweden.
    Jakobsson, Sven
    Stockholm University, Sweden.
    Birkhead, Tim R.
    University of Sheffield, UK.
    Sophisticated sperm allocation in male fowl2003In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 426, p. 70-74Article in journal (Refereed)
    Abstract [en]

    When a female is sexually promiscuous, the ejaculates of different males compete for the fertilization of her eggs; the more sperm a male inseminates into a female, the more likely he is to fertilize her eggs. Because sperm production is limited and costly, theory predicts that males will strategically allocate sperm (1) according to female promiscuity, (2) saving some for copulations with new females, and (3) to females producing more and/or better offspring. Whether males allocate sperm in all of these ways is not known, particularly in birds where the collection of natural ejaculates only recently became possible. Here we demonstrate male sperm allocation of unprecedented sophistication in the fowl Gallus gallus. Males show status-dependent sperm investment in females according to the level of female promiscuity; they progressively reduce sperm investment in a particular female but, on encountering a new female, instantaneously increase their sperm investment; and they preferentially allocate sperm to females with large sexual ornaments signalling superior maternal investment. Our results indicate that female promiscuity leads to the evolution of sophisticated male sexual behaviour.

  • 26.
    Rubin, Carl-Johan
    et al.
    Uppsala University.
    Zody, Michael C.
    Uppsala University, Broad Institute of Harvard.
    Meadows, Jennifer R. S.
    Uppsala University.
    Sherwood, Ellen
    Karolinska Institutet.
    Webster, Matthew
    Uppsala University.
    Jiang, Lin
    Uppsala University.
    Ingman, Max
    The Rudbeck Laboratory, Uppsala University.
    Sharpe, Ted
    Broad Institute of Harvard and MIT.
    Ka, Sojeong
    Department of Neurosceince, Uppsala University.
    Hallböök, Finn
    Department of Neurosceince, Uppsala University.
    Besnier, Francois
    Swedish University of Agricultural Sciences.
    Carlborg, Örjan
    Swedish University of Agricultural Sciences.
    Bed'hom, Bertrand
    INRA, AgroPArisTech.
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Zoology. Linköping University, The Institute of Technology.
    Siegel, Paul
    Virginia Polytechnic Institute and State University.
    Lindblad-Toh, Kerstin
    Uppsala University, Broad Institute of Harvard and MIT.
    Andersson, Leif
    Uppsala University, Swedish University of Agricultural Sciences.
    Whole-genome resequencing reveals loci under selection during chicken domestication2010In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 464, p. 587-591Article in journal (Refereed)
    Abstract [en]

    Domestic animals are excellent models for genetic studies of phenotypic evolution(1-3). They have evolved genetic adaptations to a new environment, the farm, and have been subjected to strong human-driven selection leading to remarkable phenotypic changes in morphology, physiology and behaviour. Identifying the genetic changes underlying these developments provides new insight into general mechanisms by which genetic variation shapes phenotypic diversity. Here we describe the use of massively parallel sequencing to identify selective sweeps of favourable alleles and candidate mutations that have had a prominent role in the domestication of chickens (Gallus gallus domesticus) and their subsequent specialization into broiler (meat-producing) and layer (egg-producing) chickens. We have generated 44.5-fold coverage of the chicken genome using pools of genomic DNA representing eight different populations of domestic chickens as well as red jungle fowl (Gallus gallus), the major wild ancestor(4). We report more than 7,000,000 single nucleotide polymorphisms, almost 1,300 deletions and a number of putative selective sweeps. One of the most striking selective sweeps found in all domestic chickens occurred at the locus for thyroid stimulating hormone receptor (TSHR), which has a pivotal role in metabolic regulation and photoperiod control of reproduction in vertebrates. Several of the selective sweeps detected in broilers overlapped genes associated with growth, appetite and metabolic regulation. We found little evidence that selection for loss-of-function mutations had a prominent role in chicken domestication, but we detected two deletions in coding sequences that we suggest are functionally important. This study has direct application to animal breeding and enhances the importance of the domestic chicken as a model organism for biomedical research.

  • 27.
    Sandewall, Erik
    Linköping University, Department of Computer and Information Science. Linköping University, The Institute of Technology.
    Systems - Opening up the process2006In: Nature, ISSN 0028-0836, E-ISSN 1476-4687Article in journal (Other academic)
    Abstract [en]

    n/a

  • 28.
    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.

  • 29.
    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.

  • 30.
    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]

      

  • 31.
    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).

  • 32.
    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.

  • 33.
    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.

  • 34.
    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.

  • 35.
    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.

  • 36.
    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)
  • 37.
    Wiltgren, Filip
    Linköping University, Faculty of Science & Engineering.
    SELF-LIMITED2016In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 535, no 7613, p. 586-586Article in journal (Other academic)
    Abstract [en]

    n/a

  • 38.
    Wiltgren, Filip
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, Faculty of Science & Engineering.
    When Nain came to Shirin’s door: Stories from the stars2018In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 557, no 7705, p. 462-462Article in journal (Other academic)
    Abstract [en]

    n/a

  • 39.
    Yvon-Durocher, Gabriel
    et al.
    University of Exeter, Penryn, UK.
    Allen, Andrew P.
    Macquarie University, Sydney, Australia .
    Bastviken, David
    Linköping University, The Tema Institute, Department of Water and Environmental Studies. Linköping University, Faculty of Arts and Sciences.
    Conrad, Ralf
    Max-Planck-Institute for Terrestrial Microbiology, Marburg, Germany .
    Gudasz, Cristian
    Umeå University, Sweden; Uppsala University, Sweden .
    St-Pierre, Annick
    University of Quebec, Canada .
    Thanh-Duc, Nguyen
    University of New Hampshire, Durham, USA.
    del Giorgio, Paul A.
    Université du Québec à Montréal, Canada.
    Methane fluxes show consistent temperature dependence across microbial to ecosystem scales2014In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 507, no 7493, p. 488-491Article in journal (Refereed)
    Abstract [en]

    Methane (CH4) is an important greenhouse gas because it has 25 times the global warming potential of carbon dioxide (CO2) by mass over a century(1). Recent calculations suggest that atmospheric CH4 emissions have been responsible for approximately 20% of Earths warming since pre-industrial times(2). Understanding how CH4 emissions from ecosystems will respond to expected increases in global temperature is therefore fundamental to predicting whether the carbon cycle will mitigate or accelerate climate change. Methanogenesis is the terminal step in the remineralization of organic matter and is carried out by strictly anaerobic Archaea(3). Like most other forms of metabolism, methanogenesis is temperature-dependent(4,5). However, it is not yet known how this physiological response combines with other biotic processes (for example, methanotrophy(6), substrate supply(3,7), microbial community composition(8)) and abiotic processes (for example, water-table depth(9,10)) to determine the temperature dependence of ecosystem-level CH4 emissions. It is also not known whether CH4 emissions at the ecosystem level have a fundamentally different temperature dependence than other key fluxes in the carbon cycle, such as photosynthesis and respiration. Here we use meta-analyses to show that seasonal variations in CH4 emissions from a wide range of ecosystems exhibit an average temperature dependence similar to that of CH4 production derived from pure cultures of methanogens and anaerobic microbial communities. This average temperature dependence (0.96 electron volts (eV)), which corresponds to a 57-fold increase between 0 and 30 degrees C, is considerably higher than previously observed for respiration (approximately 0.65 eV)(11) and photosynthesis (approximately 0.3 eV)(12). As a result, we show that both the emission of CH4 and the ratio of CH4 to CO2 emissions increase markedly with seasonal increases in temperature. Our findings suggest that global warming may have a large impact on the relative contributions of CO2 and CH4 to total greenhouse gas emissions from aquatic ecosystems, terrestrial wetlands and rice paddies.

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