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  • 101.
    Charpentier, Emmanuelle
    et al.
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Doudna, Jennifer A.
    Biotechnology: rewriting a genome2013In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 495, no 7439, p. 50-51Article in journal (Other academic)
  • 102.
    Charpentier Ljungqvist, Fredrik
    et al.
    Stockholm University, Faculty of Humanities, Department of History.
    Krusic, Paul J.
    Stockholm University, Faculty of Science, Department of Physical Geography.
    Sundqvist, Hanna S.
    Stockholm University, Faculty of Science, Department of Physical Geography.
    Zorita, Eduardo
    Brattström, Gudrun
    Stockholm University, Faculty of Science, Department of Mathematics.
    Frank, David
    Northern Hemisphere hydroclimate variability over the past twelve centuries2016In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 532, no 7597, p. 94-98Article in journal (Refereed)
    Abstract [en]

    Accurate modelling and prediction of the local to continental-scale hydroclimate response to global warming is essential given the strong impact of hydroclimate on ecosystem functioning, crop yields, water resources, and economic security. However, uncertainty in hydroclimate projections remains large, in part due to the short length of instrumental measurements available with which to assess climate models. Here we present a spatial reconstruction of hydroclimate variability over the past twelve centuries across the Northern Hemisphere derived from a network of 196 at least millennium-long proxy records. We use this reconstruction to place recent hydrological changes and future precipitation scenarios in a long-term context of spatially resolved and temporally persistent hydroclimate patterns. We find a larger percentage of land area with relatively wetter conditions in the ninth to eleventh and the twentieth centuries, whereas drier conditions are more widespread between the twelfth and nineteenth centuries. Our reconstruction reveals that prominent seesaw patterns of alternating moisture regimes observed in instrumental data across the Mediterranean, western USA, and China have operated consistently over the past twelve centuries. Using an updated compilation of 128 temperature proxy records, we assess the relationship between the reconstructed centennial-scale Northern Hemisphere hydroclimate and temperature variability. Even though dry and wet conditions occurred over extensive areas under both warm and cold climate regimes, a statistically significant co-variability of hydroclimate and temperature is evident for particular regions. We compare the reconstructed hydroclimate anomalies with coupled atmosphere-ocean general circulation model simulations and find reasonable agreement during pre-industrial times. However, the intensification of the twentieth-century-mean hydroclimate anomalies in the simulations, as compared to previous centuries, is not supported by our new multi-proxy reconstruction. This finding suggests that much work remains before we can model hydroclimate variability accurately, and highlights the importance of using palaeoclimate data to place recent and predicted hydroclimate changes in a millennium-long context.

  • 103.
    Chen, Donglei
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
    Blom, Henning
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
    Sanchez, Sophie
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology. Uppsala University, Science for Life Laboratory, SciLifeLab. European Synchrotron Radiat Facil, 6 Rue Jules Horowitz, F-38043 Grenoble, France..
    Tafforeau, Paul
    European Synchrotron Radiat Facil, 6 Rue Jules Horowitz, F-38043 Grenoble, France..
    Ahlberg, Per
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    The stem osteichthyan Andreolepis and the origin of tooth replacement2016In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 539, no 7628, p. 237-+Article in journal (Refereed)
    Abstract [en]

    The teeth of gnathostomes (jawed vertebrates) show rigidly patterned, unidirectional replacement that may or may not be associated with a shedding mechanism. These mechanisms, which are critical for the maintenance of the dentition, are incongruently distributed among extant gnathostomes. Although a permanent tooth-generating dental lamina is present in all chondrichthyans, many tetrapods and some teleosts, it is absent in the non-teleost actinopterygians. Tooth-shedding by basal hard tissue resorption occurs in most osteichthyans (including tetrapods) but not in chondrichthyans. Here we report a three-dimensional virtual dissection of the dentition of a 424-million-year-old stem osteichthyan, Andreolepis hedei, using propagation phase-contrast synchrotron microtomography, with a reconstruction of its growth history. Andreolepis, close to the common ancestor of all extant osteichthyans, shed its teeth by basal resorption but probably lacked a permanent dental lamina. This is the earliest documented instance of resorptive tooth shedding and may represent the primitive osteichthyan mode of tooth replacement.

  • 104. Chen, Richard Z
    et al.
    Pettersson, Ulf
    Whitehead Institute for Biomedical Research, Department of Biology, Cambridge, USA.
    Beard, Caroline
    Jackson-Grusby, Laurie
    Jaenisch, Rudolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Medical Genetics.
    DNA hypomethylation leads to elevated mutation rates1998In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 395, no 6697, p. 89-93Article in journal (Refereed)
    Abstract [en]

    Genome-wide demethylation has been suggested to be a step in carcinogenesis. Evidence for this notion comes from the frequently observed global DNA hypomethylation in tumour cells, and from a recent study suggesting that defects in DNA methylation might contribute to the genomic instability of some colorectal tumour cell lines. DNA hypomethylation has also been associated with abnormal chromosomal structures, as observed in cells from patients with ICF (Immunodeficiency, Centromeric instability and Facial abnormalities) syndrome and in cells treated with the demethylating agent 5-azadeoxycytidine. Here we report that murine embryonic stem cells nullizygous for the major DNA methyltransferase (Dnmt1) gene exhibited significantly elevated mutation rates at both the endogenous hypoxanthine phosphoribosyltransferase (Hprt) gene and an integrated viral thymidine kinase (tk) transgene. Gene deletions were the predominant mutations at both loci. The major cause of the observed tk deletions was either mitotic recombination or chromosomal loss accompanied by duplication of the remaining chromosome. Our results imply an important role for mammalian DNA methylation in maintaining genome stability.

  • 105. Cho, Hae Sung
    et al.
    Deng, Hexiang
    Miyasaka, Keiichi
    Dong, Zhiyue
    Cho, Minhyung
    Neimark, Alexander V.
    Kang, Jeung Ku
    Yaghi, Omar M.
    Terasaki, Osamu
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK). Graduate School of Energy, Environment, Water and Sustainability, South Korea.
    Extra adsorption and adsorbate superlattice formation in metal-organic frameworks2015In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 527, no 7579, p. 503-U193Article in journal (Refereed)
    Abstract [en]

    Metal-organic frameworks (MOFs) have a high internal surface area and widely tunable composition(1,2), which make them useful for applications involving adsorption, such as hydrogen, methane or carbon dioxide storage(3-9). The selectivity and uptake capacity of the adsorption process are determined by interactions involving the adsorbates and their porous host materials. But, although the interactions of adsorbate molecules with the internal MOF surface(10-17) and also amongst themselves within individual pores(18-22) have been extensively studied, adsorbate-adsorbate interactions across pore walls have not been explored. Here we show that local strain in the MOF, induced by pore filling, can give rise to collective and long-range adsorbate-adsorbate interactions and the formation of adsorbate superlattices that extend beyond an original MOF unit cell. Specifically, we use in situ small-angle X-ray scattering to track and map the distribution and ordering of adsorbate molecules in five members of the mesoporous MOF-74 series along entire adsorption-desorption isotherms. We find in all cases that the capillary condensation that fills the pores gives rise to the formation of 'extra adsorption domains'-that is, domains spanning several neighbouring pores, which have a higher adsorbate density than non-domain pores. In the case of one MOF, IRMOF-74-V-hex, these domains form a superlattice structure that is difficult to reconcile with the prevailing view of pore-filling as a stochastic process. The visualization of the adsorption process provided by our data, with clear evidence for initial adsorbate aggregation in distinct domains and ordering before an even distribution is finally reached, should help to improve our understanding of this process and may thereby improve our ability to exploit it practically.

  • 106. Choi, Minkee
    et al.
    Na, Kyungsu
    Kim, Jeongnam
    Sakamoto, Yasuhiro
    Terasaki, Osamu
    Stockholm University, Faculty of Science, Department of Physical, Inorganic and Structural Chemistry.
    Ryoo, Ryong
    Stable single-unit-cell nanosheets of zeolite MFI as active and long-lived catalysts2009In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 461, no 7261, p. 246-249Article in journal (Refereed)
    Abstract [en]

    Zeolites-microporous crystalline aluminosilicates-are widely used in petrochemistry and fine-chemical synthesis(1-3) because strong acid sites within their uniform micropores enable size- and shape-selective catalysis. But the very presence of the micropores, with aperture diameters below 1 nm, often goes hand-in-hand with diffusion limitations(3-5) that adversely affect catalytic activity. The problem can be overcome by reducing the thickness of the zeolite crystals, which reduces diffusion path lengths and thus improves molecular diffusion(4,5). This has been realized by synthesizing zeolite nanocrystals(6), by exfoliating layered zeolites(7-9), and by introducing mesopores in the microporous material through templating strategies(10-17) or demetallation processes(18-22). But except for the exfoliation, none of these strategies has produced 'ultrathin' zeolites with thicknesses below 5 nm. Here we show that appropriately designed bifunctional surfactants can direct the formation of zeolite structures on themesoporous and microporous length scales simultaneously and thus yield MFI (ZSM-5, one of the most important catalysts in the petrochemical industry) zeolite nanosheets that are only 2 nm thick, which corresponds to the b-axis dimension of a single MFI unit cell. The large number of acid sites on the external surface of these zeolites renders them highly active for the catalytic conversion of large organic molecules, and the reduced crystal thickness facilitates diffusion and thereby dramatically suppresses catalyst deactivation through coke deposition during methanol-to-gasoline conversion. We expect that our synthesis approach could be applied to other zeolites to improve their performance in a range of important catalytic applications.

     

  • 107. Clack, J. A.
    et al.
    Ahlberg, Per E.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Evolutionary Organism Biology.
    Finney, S. M.
    Dominguez Alonso, P.
    Robinson, J.
    Ketcham, R. A.
    A uniquely specialized ear in a very early tetrapod2003In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 425, no 6953, p. 66-69Article in journal (Refereed)
  • 108. Clark, Andrew G.
    et al.
    Eisen, Michael B.
    Smith, Douglas R.
    Bergman, Casey M.
    Oliver, Brian
    Markow, Therese A.
    Kaufman, Thomas C.
    Kellis, Manolis
    Gelbart, William
    Iyer, Venky N.
    Pollard, Daniel A.
    Sackton, Timothy B.
    Larracuente, Amanda M.
    Singh, Nadia D.
    Abad, Jose P.
    Abt, Dawn N.
    Adryan, Boris
    Aguade, Montserrat
    Akashi, Hiroshi
    Anderson, Wyatt W.
    Aquadro, Charles F.
    Ardell, David H.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, The Linnaeus Centre for Bioinformatics.
    Arguello, Roman
    Artieri, Carlo G.
    Barbash, Daniel A.
    Barker, Daniel
    Barsanti, Paolo
    Batterham, Phil
    Batzoglou, Serafim
    Begun, Dave
    Bhutkar, Arjun
    Blanco, Enrico
    Bosak, Stephanie A.
    Bradley, Robert K.
    Brand, Adrianne D.
    Brent, Michael R.
    Brooks, Angela N.
    Brown, Randall H.
    Butlin, Roger K.
    Caggese, Corrado
    Calvi, Brian R.
    de Carvalho, A. Bernardo
    Caspi, Anat
    Castrezana, Sergio
    Celniker, Susan E.
    Chang, Jean L.
    Chapple, Charles
    Chatterji, Sourav
    Chinwalla, Asif
    Civetta, Alberto
    Clifton, Sandra W.
    Comeron, Josep M.
    Costello, James C.
    Coyne, Jerry A.
    Daub, Jennifer
    David, Robert G.
    Delcher, Arthur L.
    Delehaunty, Kim
    Do, Chuong B.
    Ebling, Heather
    Edwards, Kevin
    Eickbush, Thomas
    Evans, Jay D.
    Filipski, Alan
    Findeiss, Sven
    Freyhult, Eva
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, The Linnaeus Centre for Bioinformatics.
    Fulton, Lucinda
    Fulton, Robert
    Garcia, Ana C. L.
    Gardiner, Anastasia
    Garfield, David A.
    Garvin, Barry E.
    Gibson, Greg
    Gilbert, Don
    Gnerre, Sante
    Godfrey, Jennifer
    Good, Robert
    Gotea, Valer
    Gravely, Brenton
    Greenberg, Anthony J.
    Griffiths-Jones, Sam
    Gross, Samuel
    Guigo, Roderic
    Gustafson, Erik A.
    Haerty, Wilfried
    Hahn, Matthew W.
    Halligan, Daniel L.
    Halpern, Aaron L.
    Halter, Gillian M.
    Han, Mira V.
    Heger, Andreas
    Hillier, LaDeana
    Hinrichs, Angie S.
    Holmes, Ian
    Hoskins, Roger A.
    Hubisz, Melissa J.
    Hultmark, Dan
    Huntley, Melanie A.
    Jaffe, David B.
    Jagadeeshan, Santosh
    Jeck, William R.
    Johnson, Justin
    Jones, Corbin D.
    Jordan, William C.
    Karpen, Gary H.
    Kataoka, Eiko
    Keightley, Peter D.
    Kheradpour, Pouya
    Kirkness, Ewen F.
    Koerich, Leonardo B.
    Kristiansen, Karsten
    Kudrna, Dave
    Kulathinal, Rob J.
    Kumar, Sudhir
    Kwok, Roberta
    Lander, Eric
    Langley, Charles H.
    Lapoint, Richard
    Lazzaro, Brian P.
    Lee, So-Jeong
    Levesque, Lisa
    Li, Ruiqiang
    Lin, Chiao-Feng
    Lin, Michael F.
    Lindblad-Toh, Kerstin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Llopart, Ana
    Long, Manyuan
    Low, Lloyd
    Lozovsky, Elena
    Lu, Jian
    Luo, Meizhong
    Machado, Carlos A.
    Makalowski, Wojciech
    Marzo, Mar
    Matsuda, Muneo
    Matzkin, Luciano
    McAllister, Bryant
    McBride, Carolyn S.
    McKernan, Brendan
    McKernan, Kevin
    Mendez-Lago, Maria
    Minx, Patrick
    Mollenhauer, Michael U.
    Montooth, Kristi
    Mount, Stephen M.
    Mu, Xu
    Myers, Eugene
    Negre, Barbara
    Newfeld, Stuart
    Nielsen, Rasmus
    Noor, Mohamed A. F.
    O'Grady, Patrick
    Pachter, Lior
    Papaceit, Montserrat
    Parisi, Matthew J.
    Parisi, Michael
    Parts, Leopold
    Pedersen, Jakob S.
    Pesole, Graziano
    Phillippy, Adam M.
    Ponting, Chris P.
    Pop, Mihai
    Porcelli, Damiano
    Powell, Jeffrey R.
    Prohaska, Sonja
    Pruitt, Kim
    Puig, Marta
    Quesneville, Hadi
    Ram, Kristipati Ravi
    Rand, David
    Rasmussen, Matthew D.
    Reed, Laura K.
    Reenan, Robert
    Reily, Amy
    Remington, Karin A.
    Rieger, Tania T.
    Ritchie, Michael G.
    Robin, Charles
    Rogers, Yu-Hui
    Rohde, Claudia
    Rozas, Julio
    Rubenfield, Marc J.
    Ruiz, Alfredo
    Russo, Susan
    Salzberg, Steven L.
    Sanchez-Gracia, Alejandro
    Saranga, David J.
    Sato, Hajime
    Schaeffer, Stephen W.
    Schatz, Michael C.
    Schlenke, Todd
    Schwartz, Russell
    Segarra, Carmen
    Singh, Rama S.
    Sirot, Laura
    Sirota, Marina
    Sisneros, Nicholas B.
    Smith, Chris D.
    Smith, Temple F.
    Spieth, John
    Stage, Deborah E.
    Stark, Alexander
    Stephan, Wolfgang
    Strausberg, Robert L.
    Strempel, Sebastian
    Sturgill, David
    Sutton, Granger
    Sutton, Granger G.
    Tao, Wei
    Teichmann, Sarah
    Tobari, Yoshiko N.
    Tomimura, Yoshihiko
    Tsolas, Jason M.
    Valente, Vera L. S.
    Venter, Eli
    Venter, J. Craig
    Vicario, Saverio
    Vieira, Filipe G.
    Vilella, Albert J.
    Villasante, Alfredo
    Walenz, Brian
    Wang, Jun
    Wasserman, Marvin
    Watts, Thomas
    Wilson, Derek
    Wilson, Richard K.
    Wing, Rod A.
    Wolfner, Mariana F.
    Wong, Alex
    Wong, Gane Ka-Shu
    Wu, Chung-I
    Wu, Gabriel
    Yamamoto, Daisuke
    Yang, Hsiao-Pei
    Yang, Shiaw-Pyng
    Yorke, James A.
    Yoshida, Kiyohito
    Zdobnov, Evgeny
    Zhang, Peili
    Zhang, Yu
    Zimin, Aleksey V.
    Baldwin, Jennifer
    Abdouelleil, Amr
    Abdulkadir, Jamal
    Abebe, Adal
    Abera, Brikti
    Abreu, Justin
    Acer, St Christophe
    Aftuck, Lynne
    Alexander, Allen
    An, Peter
    Anderson, Erica
    Anderson, Scott
    Arachi, Harindra
    Azer, Marc
    Bachantsang, Pasang
    Barry, Andrew
    Bayul, Tashi
    Berlin, Aaron
    Bessette, Daniel
    Bloom, Toby
    Blye, Jason
    Boguslavskiy, Leonid
    Bonnet, Claude
    Boukhgalter, Boris
    Bourzgui, Imane
    Brown, Adam
    Cahill, Patrick
    Channer, Sheridon
    Cheshatsang, Yama
    Chuda, Lisa
    Citroen, Mieke
    Collymore, Alville
    Cooke, Patrick
    Costello, Maura
    D'Aco, Katie
    Daza, Riza
    De Haan, Georgius
    DeGray, Stuart
    DeMaso, Christina
    Dhargay, Norbu
    Dooley, Kimberly
    Dooley, Erin
    Doricent, Missole
    Dorje, Passang
    Dorjee, Kunsang
    Dupes, Alan
    Elong, Richard
    Falk, Jill
    Farina, Abderrahim
    Faro, Susan
    Ferguson, Diallo
    Fisher, Sheila
    Foley, Chelsea D.
    Franke, Alicia
    Friedrich, Dennis
    Gadbois, Loryn
    Gearin, Gary
    Gearin, Christina R.
    Giannoukos, Georgia
    Goode, Tina
    Graham, Joseph
    Grandbois, Edward
    Grewal, Sharleen
    Gyaltsen, Kunsang
    Hafez, Nabil
    Hagos, Birhane
    Hall, Jennifer
    Henson, Charlotte
    Hollinger, Andrew
    Honan, Tracey
    Huard, Monika D.
    Hughes, Leanne
    Hurhula, Brian
    Husby, M. Erii
    Kamat, Asha
    Kanga, Ben
    Kashin, Seva
    Khazanovich, Dmitry
    Kisner, Peter
    Lance, Krista
    Lara, Marcia
    Lee, William
    Lennon, Niall
    Letendre, Frances
    LeVine, Rosie
    Lipovsky, Alex
    Liu, Xiaohong
    Liu, Jinlei
    Liu, Shangtao
    Lokyitsang, Tashi
    Lokyitsang, Yeshi
    Lubonja, Rakela
    Lui, Annie
    MacDonald, Pen
    Magnisalis, Vasilia
    Maru, Kebede
    Matthews, Charles
    McCusker, William
    McDonough, Susan
    Mehta, Teena
    Meldrim, James
    Meneus, Louis
    Mihai, Oana
    Mihalev, Atanas
    Mihova, Tanya
    Mittelman, Rachel
    Mlenga, Valentine
    Montmayeur, Anna
    Mulrain, Leonidas
    Navidi, Adam
    Naylor, Jerome
    Negash, Tamrat
    Nguyen, Thu
    Nguyen, Nga
    Nicol, Robert
    Norbu, Choe
    Norbu, Nyima
    Novod, Nathaniel
    O'Neill, Barry
    Osman, Sahal
    Markiewicz, Eva
    Oyono, Otero L.
    Patti, Christopher
    Phunkhang, Pema
    Pierre, Fritz
    Priest, Margaret
    Raghuraman, Sujaa
    Rege, Filip
    Reyes, Rebecca
    Rise, Cecil
    Rogov, Peter
    Ross, Keenan
    Ryan, Elizabeth
    Settipalli, Sampath
    Shea, Terry
    Sherpa, Ngawang
    Shi, Lu
    Shih, Diana
    Sparrow, Todd
    Spaulding, Jessica
    Stalker, John
    Stange-Thomann, Nicole
    Stavropoulos, Sharon
    Stone, Catherine
    Strader, Christopher
    Tesfaye, Senait
    Thomson, Talene
    Thoulutsang, Yama
    Thoulutsang, Dawa
    Topham, Kerri
    Topping, Ira
    Tsamla, Tsamla
    Vassiliev, Helen
    Vo, Andy
    Wangchuk, Tsering
    Wangdi, Tsering
    Weiand, Michael
    Wilkinson, Jane
    Wilson, Adam
    Yadav, Shailendra
    Young, Geneva
    Yu, Qing
    Zembek, Lisa
    Zhong, Danni
    Zimmer, Andrew
    Zwirko, Zac
    Alvarez, Pablo
    Brockman, Will
    Butler, Jonathan
    Chin, CheeWhye
    Grabherr, Manfred
    Kleber, Michael
    Mauceli, Evan
    MacCallum, Iain
    Evolution of genes and genomes on the Drosophila phylogeny.2007In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 450, no 7167, p. 203-218Article in journal (Refereed)
    Abstract [en]

    Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.

  • 109. Clutton-Brock, T. H.
    et al.
    Hodge, S. J.
    Spong, Göran
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Evolution, Animal Ecology.
    Russell, A. F.
    Jordan, N. R.
    Bennett, N. C.
    Sharpe, L. L.
    Manser, M. B.
    Intrasexual competition and sexual selection in cooperative mammals2006In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 444, no 7122, p. 1065-1068Article in journal (Refereed)
    Abstract [en]

    In most animals, the sex that invests least in its offspring competes more intensely for access to the opposite sex and shows greater development of secondary sexual characters than the sex that invests most(1,2). However, in some mammals where females are the primary care-givers, females compete more frequently or intensely with each other than males(3-5). A possible explanation is that, in these species, the resources necessary for successful female reproduction are heavily concentrated and intrasexual competition for breeding opportunities is more intense among females than among males. Intrasexual competition between females is likely to be particularly intense in cooperative breeders where a single female monopolizes reproduction in each group(6). Here, we use data from a twelve-year study of wild meerkats (Suricata suricatta), where females show high levels of reproductive skew, to show that females gain greater benefits from acquiring dominant status than males and traits that increase competitive ability exert a stronger influence on their breeding success. Females that acquire dominant status also develop a suite of morphological, physiological and behavioural characteristics that help them to control other group members. Our results show that sex differences in parental investment are not the only mechanism capable of generating sex differences in reproductive competition and emphasize the extent to which competition for breeding opportunities between females can affect the evolution of sex differences and the operation of sexual selection.

  • 110. Conrad, Donald F.
    et al.
    Pinto, Dalila
    Redon, Richard
    Feuk, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Gokcumen, Omer
    Zhang, Yujun
    Aerts, Jan
    Andrews, T. Daniel
    Barnes, Chris
    Campbell, Peter
    Fitzgerald, Tomas
    Hu, Min
    Ihm, Chun Hwa
    Kristiansson, Kati
    MacArthur, Daniel G.
    MacDonald, Jeffrey R.
    Onyiah, Ifejinelo
    Pang, Andy Wing Chun
    Robson, Sam
    Stirrups, Kathy
    Valsesia, Armand
    Walter, Klaudia
    Wei, John
    Tyler-Smith, Chris
    Carter, Nigel P.
    Lee, Charles
    Scherer, Stephen W.
    Hurles, Matthew E.
    Origins and functional impact of copy number variation in the human genome2010In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 464, no 7289, p. 704-712Article in journal (Refereed)
    Abstract [en]

    Structural variations of DNA greater than 1 kilobase in size account for most bases that vary among human genomes, but are still relatively under-ascertained. Here we use tiling oligonucleotide microarrays, comprising 42 million probes, to generate a comprehensive map of 11,700 copy number variations (CNVs) greater than 443 base pairs, of which most (8,599) have been validated independently. For 4,978 of these CNVs, we generated reference genotypes from 450 individuals of European, African or East Asian ancestry. The predominant mutational mechanisms differ among CNV size classes. Retrotransposition has duplicated and inserted some coding and non-coding DNA segments randomly around the genome. Furthermore, by correlation with known trait-associated single nucleotide polymorphisms (SNPs), we identified 30 loci with CNVs that are candidates for influencing disease susceptibility. Despite this, having assessed the completeness of our map and the patterns of linkage disequilibrium between CNVs and SNPs, we conclude that, for complex traits, the heritability void left by genome-wide association studies will not be accounted for by common CNVs.

  • 111. Constância, Miguel
    et al.
    Hemberger, Myriam
    Hughes, Jennifer
    Dean, Wendy
    Ferguson-Smith, Anne
    Fundele, Reinald
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Animal Development and Genetics.
    Stewart, Francesca
    Kelsey, Gavin
    Fowden, Abigail
    Sibley, Colin
    Reik, Wolf
    Placental-specific IGF-II is a major modulator of placental and fetal growth2002In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 417, no 6892, p. 945-8Article in journal (Refereed)
  • 112. Contreras, F.-Xabier
    et al.
    Ernst, Andreas M.
    Haberkant, Per
    Björkholm, Patrik
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Lindahl, Erik
    Gönen, Basak
    Tischer, Christian
    Elofsson, Arne
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    von Heijne, Gunnar
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Thiele, Christoph
    Pepperkok, Rainer
    Wieland, Felix
    Brügger, Britta
    Molecular recognition of a single sphingolipid species by a protein’s transmembrane domain2012In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 481, no 7382, p. 525-529Article in journal (Refereed)
    Abstract [en]

    Functioning and processing of membrane proteins critically depend on the way their transmembrane segments are embedded in the membrane. Sphingolipids are structural components of membranes and can also act as intracellular second messengers. Not much is known of sphingolipids binding to transmembrane domains (TMDs) of proteins within the hydrophobic bilayer, and how this could affect protein function. Here we show a direct and highly specific interaction of exclusively one sphingomyelin species, SM 18, with the TMD of the COPI machinery protein p24 (ref. 2). Strikingly, the interaction depends on both the headgroup and the backbone of the sphingolipid, and on a signature sequence (VXXTLXXIY) within the TMD. Molecular dynamics simulations show a close interaction of SM 18 with the TMD. We suggest a role of SM 18 in regulating the equilibrium between an inactive monomeric and an active oligomeric state of the p24 protein, which in turn regulates COPI-dependent transport. Bioinformatic analyses predict that the signature sequence represents a conserved sphingolipid-binding cavity in a variety of mammalian membrane proteins. Thus, in addition to a function as second messengers, sphingolipids can act as cofactors to regulate the function of transmembrane proteins. Our discovery of an unprecedented specificity of interaction of a TMD with an individual sphingolipid species adds to our understanding of why biological membranes are assembled from such a large variety of different lipids.

  • 113.
    Contreras, F.-Xabier
    et al.
    Heidelberg University.
    Ernst, Andreas M
    Heidelberg University.
    Haberkant, Per
    Heidelberg University.
    Björkholm, Patrik
    Stockholm University.
    Lindahl, Erik
    KTH, School of Engineering Sciences (SCI), Theoretical Physics, Theoretical & Computational Biophysics.
    Gönen, Başak
    Tischer, Christian
    Heidelberg University.
    Elofsson, Arne
    Stockholm University.
    von Heijne, Gunnar
    Stockholm University.
    Thiele, Christoph
    Heidelberg University.
    Pepperkok, Rainer
    Heidelberg University.
    Wieland, Felix
    Heidelberg University.
    Brügger, Britta
    Heidelberg University.
    Molecular recognition of a single sphingolipid species by a protein's transmembrane domain2012In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 481, no 7382, p. 525-529Article in journal (Refereed)
    Abstract [en]

    Functioning and processing of membrane proteins critically depend on the way their transmembrane segments are embedded in the membrane. Sphingolipids are structural components of membranes and can also act as intracellular second messengers. Not much is known of sphingolipids binding to transmembrane domains (TMDs) of proteins within the hydrophobic bilayer, and how this could affect protein function. Here we show a direct and highly specific interaction of exclusively one sphingomyelin species, SM 18, with the TMD of the COPI machinery protein p24 (ref. 2). Strikingly, the interaction depends on both the headgroup and the backbone of the sphingolipid, and on a signature sequence (VXXTLXXIY) within the TMD. Molecular dynamics simulations show a close interaction of SM 18 with the TMD. We suggest a role of SM 18 in regulating the equilibrium between an inactive monomeric and an active oligomeric state of the p24 protein, which in turn regulates COPI-dependent transport. Bioinformatic analyses predict that the signature sequence represents a conserved sphingolipid-binding cavity in a variety of mammalian membrane proteins. Thus, in addition to a function as second messengers, sphingolipids can act as cofactors to regulate the function of transmembrane proteins. Our discovery of an unprecedented specificity of interaction of a TMD with an individual sphingolipid species adds to our understanding of why biological membranes are assembled from such a large variety of different lipids.

  • 114. Coquel, Flavie
    et al.
    Silva, Maria-Joao
    Técher, Hervé
    Zadorozhny, Karina
    Sharma, Sushma
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Nieminuszczy, Jadwiga
    Mettling, Clément
    Dardillac, Elodie
    Barthe, Antoine
    Schmitz, Anne-Lyne
    Promonet, Alexy
    Cribier, Alexandra
    Sarrazin, Amélie
    Niedzwiedz, Wojciech
    Lopez, Bernard
    Costanzo, Vincenzo
    Krejci, Lumir
    Chabes, Andrei
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Benkirane, Monsef
    Lin, Yea-Lih
    Pasero, Philippe
    SAMHD1 acts at stalled replication forks to prevent interferon induction2018In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 557, no 7703, p. 57-61Article in journal (Refereed)
    Abstract [en]

    SAMHD1 was previously characterized as a dNTPase that protects cells from viral infections. Mutations in SAMHD1 are implicated in cancer development and in a severe congenital inflammatory disease known as Aicardi-Goutières syndrome. The mechanism by which SAMHD1 protects against cancer and chronic inflammation is unknown. Here we show that SAMHD1 promotes degradation of nascent DNA at stalled replication forks in human cell lines by stimulating the exonuclease activity of MRE11. This function activates the ATR-CHK1 checkpoint and allows the forks to restart replication. In SAMHD1-depleted cells, single-stranded DNA fragments are released from stalled forks and accumulate in the cytosol, where they activate the cGAS-STING pathway to induce expression of pro-inflammatory type I interferons. SAMHD1 is thus an important player in the replication stress response, which prevents chronic inflammation by limiting the release of single-stranded DNA from stalled replication forks.

  • 115. Craddock, Nick
    et al.
    Hurles, Matthew E.
    Cardin, Niall
    Pearson, Richard D.
    Plagnol, Vincent
    Robson, Samuel
    Vukcevic, Damjan
    Barnes, Chris
    Conrad, Donald F.
    Giannoulatou, Eleni
    Holmes, Chris
    Marchini, Jonathan L.
    Stirrups, Kathy
    Tobin, Martin D.
    Wain, Louise V.
    Yau, Chris
    Aerts, Jan
    Ahmad, Tariq
    Andrews, T. Daniel
    Arbury, Hazel
    Attwood, Anthony
    Auton, Adam
    Ball, Stephen G.
    Balmforth, Anthony J.
    Barrett, Jeffrey C.
    Barroso, Ines
    Barton, Anne
    Bennett, Amanda J.
    Bhaskar, Sanjeev
    Blaszczyk, Katarzyna
    Bowes, John
    Brand, Oliver J.
    Braund, Peter S.
    Bredin, Francesca
    Breen, Gerome
    Brown, Morris J.
    Bruce, Ian N.
    Bull, Jaswinder
    Burren, Oliver S.
    Burton, John
    Byrnes, Jake
    Caesar, Sian
    Clee, Chris M.
    Coffey, Alison J.
    Connell, John M. C.
    Cooper, Jason D.
    Dominiczak, Anna F.
    Downes, Kate
    Drummond, Hazel E.
    Dudakia, Darshna
    Dunham, Andrew
    Ebbs, Bernadette
    Eccles, Diana
    Edkins, Sarah
    Edwards, Cathryn
    Elliot, Anna
    Emery, Paul
    Evans, David M.
    Evans, Gareth
    Eyre, Steve
    Farmer, Anne
    Ferrier, I. Nicol
    Feuk, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Fitzgerald, Tomas
    Flynn, Edward
    Forbes, Alistair
    Forty, Liz
    Franklyn, Jayne A.
    Freathy, Rachel M.
    Gibbs, Polly
    Gilbert, Paul
    Gokumen, Omer
    Gordon-Smith, Katherine
    Gray, Emma
    Green, Elaine
    Groves, Chris J.
    Grozeva, Detelina
    Gwilliam, Rhian
    Hall, Anita
    Hammond, Naomi
    Hardy, Matt
    Harrison, Pile
    Hassanali, Neelam
    Hebaishi, Husam
    Hines, Sarah
    Hinks, Anne
    Hitman, Graham A.
    Hocking, Lynne
    Howard, Eleanor
    Howard, Philip
    Howson, Joanna M. M.
    Hughes, Debbie
    Hunt, Sarah
    Isaacs, John D.
    Jain, Mahim
    Jewell, Derek P.
    Johnson, Toby
    Jolley, Jennifer D.
    Jones, Ian R.
    Jones, Lisa A.
    Kirov, George
    Langford, Cordelia F.
    Lango-Allen, Hana
    Lathrop, G. Mark
    Lee, James
    Lee, Kate L.
    Lees, Charlie
    Lewis, Kevin
    Lindgren, Cecilia M.
    Maisuria-Armer, Meeta
    Maller, Julian
    Mansfield, John
    Martin, Paul
    Massey, Dunecan C. O.
    McArdle, Wendy L.
    McGuffin, Peter
    McLay, Kirsten E.
    Mentzer, Alex
    Mimmack, Michael L.
    Morgan, Ann E.
    Morris, Andrew P.
    Mowat, Craig
    Myers, Simon
    Newman, William
    Nimmo, Elaine R.
    O'Donovan, Michael C.
    Onipinla, Abiodun
    Onyiah, Ifejinelo
    Ovington, Nigel R.
    Owen, Michael J.
    Palin, Kimmo
    Parnell, Kirstie
    Pernet, David
    Perry, John R. B.
    Phillips, Anne
    Pinto, Dalila
    Prescott, Natalie J.
    Prokopenko, Inga
    Quail, Michael A.
    Rafelt, Suzanne
    Rayner, Nigel W.
    Redon, Richard
    Reid, David M.
    Renwick, Anthony
    Ring, Susan M.
    Robertson, Neil
    Russell, Ellie
    St Clair, David
    Sambrook, Jennifer G.
    Sanderson, Jeremy D.
    Schuilenburg, Helen
    Scott, Carol E.
    Scott, Richard
    Seal, Sheila
    Shaw-Hawkins, Sue
    Shields, Beverley M.
    Simmonds, Matthew J.
    Smyth, Debbie J.
    Somaskantharajah, Elilan
    Spanova, Katarina
    Steer, Sophia
    Stephens, Jonathan
    Stevens, Helen E.
    Stone, Millicent A.
    Su, Zhan
    Symmons, Deborah P. M.
    Thompson, John R.
    Thomson, Wendy
    Travers, Mary E.
    Turnbull, Clare
    Valsesia, Armand
    Walker, Mark
    Walker, Neil M.
    Wallace, Chris
    Warren-Perry, Margaret
    Watkins, Nicholas A.
    Webster, John
    Weedon, Michael N.
    Wilson, Anthony G.
    Woodburn, Matthew
    Wordsworth, B. Paul
    Young, Allan H.
    Zeggini, Eleftheria
    Carter, Nigel P.
    Frayling, Timothy M.
    Lee, Charles
    McVean, Gil
    Munroe, Patricia B.
    Palotie, Aarno
    Sawcer, Stephen J.
    Scherer, Stephen W.
    Strachan, David P.
    Tyler-Smith, Chris
    Brown, Matthew A.
    Burton, Paul R.
    Caulfield, Mark J.
    Compston, Alastair
    Farrall, Martin
    Gough, Stephen C. L.
    Hall, Alistair S.
    Hattersley, Andrew T.
    Hill, Adrian V. S.
    Mathew, Christopher G.
    Pembrey, Marcus
    Satsangi, Jack
    Stratton, Michael R.
    Worthington, Jane
    Deloukas, Panos
    Duncanson, Audrey
    Kwiatkowski, Dominic P.
    McCarthy, Mark I.
    Ouwehand, Willem H.
    Parkes, Miles
    Rahman, Nazneen
    Todd, John A.
    Samani, Nilesh J.
    Donnelly, Peter
    Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls2010In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 464, no 7289, p. 713-720Article in journal (Refereed)
    Abstract [en]

    Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed,19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated similar to 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.

  • 116. Craig, O. E.
    et al.
    Saul, H.
    Lucquin, A.
    Nishida, Y.
    Tache, K.
    Clarke, L.
    Thompson, A.
    Altoft, D. T.
    Uchiyama, J.
    Ajimoto, M.
    Gibbs, K.
    Isaksson, Sven
    Stockholm University, Faculty of Humanities, Department of Archaeology and Classical Studies, Archaeological Research Laboratory. Stockholm University, Faculty of Humanities, Centre for the Study of Cultural Evolution.
    Heron, C. P.
    Jordan, P.
    Earliest evidence for the use of pottery2013In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 496, p. 351-354Article in journal (Refereed)
    Abstract [en]

    Pottery was a hunter-gatherer innovation that first emerged in East Asia between 20,000 and 12,000 calibrated years before present(1,2) (cal BP), towards the end of the Late Pleistocene epoch, a period of time when humans were adjusting to changing climates and new environments. Ceramic container technologies were one of a range of late glacial adaptations that were pivotal to structuring subsequent cultural trajectories in different regions of the world, but the reasons for their emergence and widespread uptake are poorly understood. The first ceramic containers must have provided prehistoric hunter-gatherers with attractive new strategies for processing and consuming foodstuffs, but virtually nothing is known of how early pots were used. Here we report the chemical analysis of food residues associated with Late Pleistocene pottery, focusing on one of the best-studied prehistoric ceramic sequences in the world, the Japanese Jomon. We demonstrate that lipids can be recovered reliably from charred surface deposits adhering to pottery dating from about 15,000 to 11,800 cal BP (the Incipient Jomon period), the oldest pottery so far investigated, and that in most cases these organic compounds are unequivocally derived from processing freshwater and marine organisms. Stable isotope data support the lipid evidence and suggest that most of the 101 charred deposits analysed, from across the major islands of Japan, were derived from high-trophic-level aquatic food. Productive aquatic ecotones were heavily exploited by late glacial foragers(3), perhaps providing an initial impetus for investment in ceramic container technology, and paving the way for further intensification of pottery use by hunter-gatherers in the early Holocene epoch. Now that we have shown that it is possible to analyse organic residues from some of the world's earliest ceramic vessels, the subsequent development of this critical technology can be clarified through further widespread testing of hunter-gatherer pottery from later periods.

  • 117. Cressey, Daniel
    Geology: The next land rush2008In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 451, no 7174, p. 12-15Article in journal (Refereed)
  • 118. Curtis, Bruce A.
    et al.
    Tanifuji, Goro
    Burki, Fabien
    Gruber, Ansgar
    Irimia, Manuel
    Maruyama, Shinichiro
    Arias, Maria C.
    Ball, Steven G.
    Gile, Gillian H.
    Hirakawa, Yoshihisa
    Hopkins, Julia F.
    Kuo, Alan
    Rensing, Stefan A.
    Schmutz, Jeremy
    Symeonidi, Aikaterini
    Elias, Marek
    Eveleigh, Robert J. M.
    Herman, Emily K.
    Klute, Mary J.
    Nakayama, Takuro
    Obornik, Miroslav
    Reyes-Prieto, Adrian
    Armbrust, E. Virginia
    Aves, Stephen J.
    Beiko, Robert G.
    Coutinho, Pedro
    Dacks, Joel B.
    Durnford, Dion G.
    Fast, Naomi M.
    Green, Beverley R.
    Grisdale, Cameron J.
    Hempel, Franziska
    Henrissat, Bernard
    Höppner, Marc P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Ishida, Ken-Ichiro
    Kim, Eunsoo
    Koreny, Lude. K.
    Kroth, Peter G.
    Liu, Yuan
    Malik, Shehre-Banoo
    Maier, Uwe G.
    McRose, Darcy
    Mock, Thomas
    Neilson, Jonathan A. D.
    Onodera, Naoko T.
    Poole, Anthony M.
    Pritham, Ellen J.
    Richards, Thomas A.
    Rocap, Gabrielle
    Roy, Scott W.
    Sarai, Chihiro
    Schaack, Sarah
    Shirato, Shu
    Slamovits, Claudio H.
    Spencer, David F.
    Suzuki, Shigekatsu
    Worden, Alexandra Z.
    Zauner, Stefan
    Barry, Kerrie
    Bell, Callum
    Bharti, Arvind K.
    Crow, John A.
    Grimwood, Jane
    Kramer, Robin
    Lindquist, Erika
    Lucas, Susan
    Salamov, Asaf
    McFadden, Geoffrey I.
    Lane, Christopher E.
    Keeling, Patrick J.
    Gray, Michael W.
    Grigoriev, Igor V.
    Archibald, John M.
    Algal genomes reveal evolutionary mosaicism and the fate of nucleomorphs2012In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 492, no 7427, p. 59-65Article in journal (Refereed)
    Abstract [en]

    Cryptophyte and chlorarachniophyte algae are transitional forms in the widespread secondary endosymbiotic acquisition of photosynthesis by engulfment of eukaryotic algae. Unlike most secondary plastid-bearing algae, miniaturized versions of the endosymbiont nuclei (nucleomorphs) persist in cryptophytes and chlorarachniophytes. To determine why, and to address other fundamental questions about eukaryote-eukaryote endosymbiosis, we sequenced the nuclear genomes of the cryptophyte Guillardia theta and the chlorarachniophyte Bigelowiella natans. Both genomes have >21,000 protein genes and are intron rich, and B. natans exhibits unprecedented alternative splicing for a single-celled organism. Phylogenomic analyses and subcellular targeting predictions reveal extensive genetic and biochemical mosaicism, with both host-and endosymbiont-derived genes servicing the mitochondrion, the host cell cytosol, the plastid and the remnant endosymbiont cytosol of both algae. Mitochondrion-to-nucleus gene transfer still occurs in both organisms but plastid-to-nucleus and nucleomorph-to-nucleus transfers do not, which explains why a small residue of essential genes remains locked in each nucleomorph.

  • 119. Dahl-Jensen, D.
    et al.
    Albert, M. R.
    Aldahan, A.
    Azuma, N.
    Balslev-Clausen, D.
    Baumgartner, M.
    Berggren, A. -M
    Bigler, M.
    Binder, T.
    Blunier, T.
    Bourgeois, J. C.
    Brook, E. J.
    Buchardt, S. L.
    Buizert, C.
    Capron, E.
    Chappellaz, J.
    Chung, J.
    Clausen, H. B.
    Cvijanovic, I.
    Davies, S. M.
    Ditlevsen, P.
    Eicher, O.
    Fischer, H.
    Fisher, D. A.
    Fleet, L. G.
    Gfeller, G.
    Gkinis, V.
    Gogineni, S.
    Goto-Azuma, K.
    Grinsted, A.
    Gudlaugsdottir, H.
    Guillevic, M.
    Hansen, S. B.
    Hansson, Margareta
    Stockholm University, Faculty of Science, Department of Physical Geography and Quaternary Geology.
    Hirabayashi, M.
    Hong, S.
    Hur, S. D.
    Huybrechts, P.
    Hvidberg, C. S.
    Iizuka, Yoshinori
    Stockholm University, Faculty of Science, Department of Physical Geography and Quaternary Geology. Hokkaido University, Japan.
    Jenk, T.
    Johnsen, S. J.
    Jones, T. R.
    Jouzel, J.
    Karlsson, N. B.
    Kawamura, K.
    Keegan, K.
    Kettner, E.
    Kipfstuhl, S.
    Kjaer, H. A.
    Koutnik, M.
    Kuramoto, T.
    Koehler, P.
    Laepple, T.
    Landais, A.
    Langen, P. L.
    Larsen, L. B.
    Leuenberger, D.
    Leuenberger, M.
    Leuschen, C.
    Li, J.
    Lipenkov, V.
    Martinerie, P.
    Maselli, O. J.
    Masson-Delmotte, V.
    McConnell, J. R.
    Miller, H.
    Mini, O.
    Miyamoto, A.
    Montagnat-Rentier, M.
    Mulvaney, R.
    Muscheler, R.
    Orsi, A. J.
    Paden, J.
    Panton, C.
    Pattyn, F.
    Petit, J. -R
    Pol, K.
    Popp, T.
    Possnert, G.
    Prie, F.
    Prokopiou, M.
    Quiquet, A.
    Rasmussen, S. O.
    Raynaud, D.
    Ren, J.
    Reutenauer, C.
    Ritz, C.
    Rockmann, T.
    Rosen, J. L.
    Rubino, M.
    Rybak, O.
    Samyn, D.
    Sapart, C. J.
    Schilt, A.
    Schmidt, A. M. Z.
    Schwander, J.
    Schuepbach, S.
    Seierstad, I.
    Severinghaus, J. P.
    Sheldon, S.
    Simonsen, S. B.
    Sjolte, J.
    Solgaard, A. M.
    Sowers, T.
    Sperlich, P.
    Steen-Larsen, H. C.
    Steffen, K.
    Steffensen, J. P.
    Steinhage, D.
    Stocker, T. F.
    Stowasser, C.
    Sturevik, A. S.
    Sturges, W. T.
    Sveinbjornsdottir, A.
    Svensson, A.
    Tison, J. -L
    Uetake, J.
    Vallelonga, P.
    van de Wal, R. S. W.
    van der Wel, G.
    Vaughn, B. H.
    Vinther, B.
    Waddington, E.
    Wegner, A.
    Weikusat, I.
    White, J. W. C.
    Wilhelms, F.
    Winstrup, M.
    Witrant, E.
    Wolff, E. W.
    Xiao, C.
    Zheng, J.
    Eemian interglacial reconstructed from a Greenland folded ice core2013In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 493, no 7433, p. 489-494Article in journal (Refereed)
    Abstract [en]

    Efforts to extract a Greenland ice core with a complete record of the Eemian interglacial (130,000 to 115,000 years ago) have until now been unsuccessful. The response of the Greenland ice sheet to the warmer-than-present climate of the Eemian has thus remained unclear. Here we present the new North Greenland Eemian Ice Drilling ('NEEM') ice core and show only a modest ice-sheet response to the strong warming in the early Eemian. We reconstructed the Eemian record from folded ice using globally homogeneous parameters known from dated Greenland and Antarctic ice-core records. On the basis of water stable isotopes, NEEM surface temperatures after the onset of the Eemian (126,000 years ago) peaked at 8 +/- 4 degrees Celsius above the mean of the past millennium, followed by a gradual cooling that was probably driven by the decreasing summer insolation. Between 128,000 and 122,000 years ago, the thickness of the northwest Greenland ice sheet decreased by 400 +/- 250 metres, reaching surface elevations 122,000 years ago of 130 +/- 300 metres lower than the present. Extensive surface melt occurred at the NEEM site during the Eemian, a phenomenon witnessed when melt layers formed again at NEEM during the exceptional heat of July 2012. With additional warming, surface melt might become more common in the future.

  • 120. Dahl-Jensen, D.
    et al.
    Albert, M. R.
    Aldahan, Ala
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, LUVAL.
    Azuma, N.
    Balslev-Clausen, D.
    Baumgartner, M.
    Berggren, Ann-Marie
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences.
    Bigler, M.
    Binder, T.
    Blunier, T.
    Bourgeois, J. C.
    Brook, E. J.
    Buchardt, S. L.
    Buizert, C.
    Capron, E.
    Chappellaz, J.
    Chung, J.
    Clausen, H. B.
    Cvijanovic, I.
    Davies, S. M.
    Ditlevsen, P.
    Eicher, O.
    Fischer, H.
    Fisher, D. A.
    Fleet, L. G.
    Gfeller, G.
    Gkinis, V.
    Gogineni, S.
    Goto-Azuma, K.
    Grinsted, A.
    Gudlaugsdottir, H.
    Guillevic, M.
    Hansen, S. B.
    Hansson, M.
    Hirabayashi, M.
    Hong, S.
    Hur, S. D.
    Huybrechts, P.
    Hvidberg, C. S.
    Iizuka, Y.
    Jenk, T.
    Johnsen, S. J.
    Jones, T. R.
    Jouzel, J.
    Karlsson, N. B.
    Kawamura, K.
    Keegan, K.
    Kettner, E.
    Kipfstuhl, S.
    Kjaer, H. A.
    Koutnik, M.
    Kuramoto, T.
    Koehler, P.
    Laepple, T.
    Landais, A.
    Langen, P. L.
    Larsen, L. B.
    Leuenberger, D.
    Leuenberger, M.
    Leuschen, C.
    Li, J.
    Lipenkov, V.
    Martinerie, P.
    Maselli, O. J.
    Masson-Delmotte, V.
    McConnell, J. R.
    Miller, H.
    Mini, O.
    Miyamoto, A.
    Montagnat-Rentier, M.
    Mulvaney, R.
    Muscheler, R.
    Orsi, A. J.
    Paden, J.
    Panton, C.
    Pattyn, F.
    Petit, J. -R
    Pol, K.
    Popp, T.
    Possnert, Göran
    Uppsala University, Disciplinary Domain of Science and Technology, För teknisk-naturvetenskapliga fakulteten gemensamma enheter, Tandem Laboratory.
    Prie, F.
    Prokopiou, M.
    Quiquet, A.
    Rasmussen, S. O.
    Raynaud, D.
    Ren, J.
    Reutenauer, C.
    Ritz, C.
    Rockmann, T.
    Rosen, J. L.
    Rubino, M.
    Rybak, O.
    Samyn, D.
    Sapart, C. J.
    Schilt, A.
    Schmidt, A. M. Z.
    Schwander, J.
    Schuepbach, S.
    Seierstad, I.
    Severinghaus, J. P.
    Sheldon, S.
    Simonsen, S. B.
    Sjolte, J.
    Solgaard, A. M.
    Sowers, T.
    Sperlich, P.
    Steen-Larsen, H. C.
    Steffen, K.
    Steffensen, J. P.
    Steinhage, D.
    Stocker, T. F.
    Stowasser, C.
    Sturevik, A. S.
    Sturges, W. T.
    Sveinbjornsdottir, A.
    Svensson, A.
    Tison, J. -L
    Uetake, J.
    Vallelonga, P.
    van de Wal, R. S. W.
    van der Wel, G.
    Vaughn, B. H.
    Vinther, B.
    Waddington, E.
    Wegner, A.
    Weikusat, I.
    White, J. W. C.
    Wilhelms, F.
    Winstrup, M.
    Witrant, E.
    Wolff, E. W.
    Xiao, C.
    Zheng, J.
    Eemian interglacial reconstructed from a Greenland folded ice core2013In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 493, no 7433, p. 489-494Article in journal (Refereed)
    Abstract [en]

    Efforts to extract a Greenland ice core with a complete record of the Eemian interglacial (130,000 to 115,000 years ago) have until now been unsuccessful. The response of the Greenland ice sheet to the warmer-than-present climate of the Eemian has thus remained unclear. Here we present the new North Greenland Eemian Ice Drilling ('NEEM') ice core and show only a modest ice-sheet response to the strong warming in the early Eemian. We reconstructed the Eemian record from folded ice using globally homogeneous parameters known from dated Greenland and Antarctic ice-core records. On the basis of water stable isotopes, NEEM surface temperatures after the onset of the Eemian (126,000 years ago) peaked at 8 +/- 4 degrees Celsius above the mean of the past millennium, followed by a gradual cooling that was probably driven by the decreasing summer insolation. Between 128,000 and 122,000 years ago, the thickness of the northwest Greenland ice sheet decreased by 400 +/- 250 metres, reaching surface elevations 122,000 years ago of 130 +/- 300 metres lower than the present. Extensive surface melt occurred at the NEEM site during the Eemian, a phenomenon witnessed when melt layers formed again at NEEM during the exceptional heat of July 2012. With additional warming, surface melt might become more common in the future.

  • 121. D'Alisa, Giacomo
    et al.
    Armiero, Marco
    KTH, School of Architecture and the Built Environment (ABE), Philosophy and History of Technology, History of Science, Technology and Environment.
    De Rosa, Salvatore Paolo
    Rethink Campania's toxic-waste scandal2014In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 509, no 7501, p. 427-427Article in journal (Refereed)
  • 122. Daumke, Oliver
    et al.
    Lundmark, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Vallis, Yvonne
    Martens, Sascha
    Butler, P Jonathan G
    McMahon, Harvey T
    Architectural and mechanistic insights into an EHD ATPase involved in membrane remodelling2007In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 449, no 7164, p. 923-927Article in journal (Refereed)
    Abstract [en]

    The ability to actively remodel membranes in response to nucleotide hydrolysis has largely been attributed to GTPases of the dynamin superfamily, and these have been extensively studied. Eps15 homology (EH)-domain-containing proteins (EHDs/RME-1/pincher) comprise a less-well-characterized class of highly conserved eukaryotic ATPases implicated in clathrin-independent endocytosis, and recycling from endosomes. Here we show that EHDs share many common features with the dynamin superfamily, such as a low affinity for nucleotides, the ability to tubulate liposomes in vitro, oligomerization around lipid tubules in ring-like structures and stimulated nucleotide hydrolysis in response to lipid binding. We present the structure of EHD2, bound to a non-hydrolysable ATP analogue, and provide evidence consistent with a role for EHDs in nucleotide-dependent membrane remodelling in vivo. The nucleotide-binding domain is involved in dimerization, which creates a highly curved membrane-binding region in the dimer. Oligomerization of dimers occurs on another interface of the nucleotide-binding domain, and this allows us to model the EHD oligomer. We discuss the functional implications of the EHD2 structure for understanding membrane deformation.

  • 123. de lavergne, C.
    et al.
    Madec, G.
    Roquet, Fabien
    Stockholm University, Faculty of Science, Department of Meteorology .
    Holmes, R. M.
    McDougall, T. J.
    Abyssal ocean overturning shaped by seafloor distribution2017In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 551, no 7679, p. 181-186Article in journal (Refereed)
    Abstract [en]

    The abyssal ocean is broadly characterized by northward flow of the densest waters and southward flow of less-dense waters above them. Understanding what controls the strength and structure of these interhemispheric flows-referred to as the abyssal overturning circulation-is key to quantifying the ocean's ability to store carbon and heat on timescales exceeding a century. Here we show that, north of 32 degrees S, the depth distribution of the seafloor compels dense southernorigin waters to flow northward below a depth of about 4 kilometres and to return southward predominantly at depths greater than 2.5 kilometres. Unless ventilated from the north, the overlying mid-depths (1 to 2.5 kilometres deep) host comparatively weak mean meridional flow. Backed by analysis of historical radiocarbon measurements, the findings imply that the geometry of the Pacific, Indian and Atlantic basins places a major external constraint on the overturning structure.

  • 124. de Vries, B. L.
    et al.
    Acke, B.
    Blommaert, J. A. D. L.
    Waelkens, C.
    Waters, L. B. F. M.
    Vandenbussche, B.
    Min, M.
    Olofsson, Göran
    Stockholm University, Faculty of Science, Department of Astronomy.
    Dominik, C.
    Decin, L.
    Barlow, M. J.
    Brandeker, Alexis
    Stockholm University, Faculty of Science, Department of Astronomy.
    Di Francesco, J.
    Glauser, A. M.
    Greaves, J.
    Harvey, P. M.
    Holland, W. S.
    Ivison, R. J.
    Liseau, R.
    Pantin, E. E.
    Pilbratt, G. L.
    Royer, P.
    Sibthorpe, B.
    Comet-like mineralogy of olivine crystals in an extrasolar proto-Kuiper belt2012In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 490, no 7418, p. 74-76Article in journal (Refereed)
    Abstract [en]

    Some planetary systems harbour debris disks containing planetesimals such as asteroids and comets(1). Collisions between such bodies produce small dust particles(2), the spectral features of which reveal their composition and, hence, that of their parent bodies. A measurement of the composition of olivine crystals (Mg2-2xFe2xSiO4) has been done for the protoplanetary disk HD 100546 (refs 3, 4) and for olivine crystals in the warm inner parts of planetary systems. The latter compares well with the iron-rich olivine in asteroids(5,6) (x approximate to 0.29). In the cold outskirts of the beta Pictoris system, an analogue to the young Solar System, olivine crystals were detected(7) but their composition remained undetermined, leaving unknown how the composition of the bulk of Solar System cometary olivine grains compares with that of extrasolar comets(8,9). Here we report the detection of the 69-micrometre-wavelength band of olivine crystals in the spectrum of beta Pictoris. Because the disk is optically thin, we can associate the crystals with an extrasolar proto-Kuiper belt a distance of 15-45 astronomical units from the star (one astronomical unit is the Sun-Earth distance), determine their magnesium-rich composition (x = 0.01 +/- 0.001) and show that they make up 3.6 +/- 1.0 per cent of the total dust mass. These values are strikingly similar to those for the dust emitted by the most primitive comets in the Solar System(8-10), even though beta Pictoris is more massive and more luminous and has a different planetary system architecture.

  • 125. Decin, L.
    et al.
    Agundez, M.
    Barlow, M. J.
    Daniel, F.
    Cernicharo, J.
    Lombaert, R.
    De Beck, E.
    Royer, P.
    Vandenbussche, B.
    Wesson, R.
    Polehampton, E. T.
    Blommaert, J. A. D. L.
    De Meester, W.
    Exter, K.
    Feuchtgruber, H.
    Gear, W. K.
    Gomez, H. L.
    Groenewegen, M. A. T.
    Guelin, M.
    Hargrave, P. C.
    Huygen, R.
    Imhof, P.
    Ivison, R. J.
    Jean, C.
    Kahane, C.
    Kerschbaum, F.
    Leeks, S. J.
    Lim, T.
    Matsuura, M.
    Olofsson, Göran
    Stockholm University, Faculty of Science, Department of Astronomy.
    Posch, T.
    Regibo, S.
    Savini, G.
    Sibthorpe, B.
    Swinyard, B. M.
    Yates, J. A.
    Waelkens, C.
    Warm water vapour in the sooty outflow from a luminous carbon star2010In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 467, no 7311, p. 64-67Article in journal (Refereed)
    Abstract [en]

    The detection(1) of circumstellar water vapour around the ageing carbon star IRC + 10216 challenged the current understanding of chemistry in old stars, because water was predicted(2) to be almost absent in carbon-rich stars. Several explanations for the water were postulated, including the vaporization of icy bodies (comets or dwarf planets) in orbit around the star(1), grain surface reactions(3), and photochemistry in the outer circumstellar envelope(4). With a single water line detected so far from this one carbon-rich evolved star, it is difficult to discriminate between the different mechanisms proposed. Here we report the detection of dozens of water vapour lines in the far-infrared and sub-millimetre spectrum of IRC + 10216 using the Herschel satellite(5). This includes some high-excitation lines with energies corresponding to similar to 1,000 K, which can be explained only if water is present in the warm inner sooty region of the envelope. A plausible explanation for the warm water appears to be the penetration of ultraviolet photons deep into a clumpy circumstellar envelope. This mechanism also triggers the formation of other molecules, such as ammonia, whose observed abundances(6) are much higher than hitherto predicted(7).

  • 126. DeLuca, T H
    et al.
    Zackrisson, O
    Nilsson, M C
    Sellstedt, Anita
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Quantifying nitrogen-fixation in feather moss carpets of boreal forests2002In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 419, no 6910, p. 917-920Article in journal (Refereed)
    Abstract [en]

    Biological nitrogen (N) fixation is the primary source of N within natural ecosystems(1), yet the origin of boreal forest N has remained elusive. The boreal forests of Eurasia and North America lack any significant, widespread symbiotic N-fixing plants(1-6). With the exception of scattered stands of alder in early primary successional forests(7), N-fixation in boreal forests is considered to be extremely limited. Nitrogen-fixation in northern European boreal forests has been estimated(2) at only 0.5 kg Nha(-1) yr(-1); however, organic N is accumulated in these ecosystems at a rate of 3 kg N ha(-1) yr(-1) (ref. 8). Our limited understanding of the origin of boreal N is unacceptable given the extent of the boreal forest region, but predictable given our imperfect knowledge of N-fixation(1,9). Herein we report on a N-fixing symbiosis between a cyanobacterium (Nostoc sp.) and the ubiquitous feather moss, Pleurozium schreberi (Bird) Mitt. that alone fixes between 1.5 and 2.0 kg N ha(-1) yr(-1) in mid- to late-successional forests of northern Scandinavia and Finland. Previous efforts have probably underestimated N-fixation potential in boreal forests.

  • 127.
    Deodhar, Ganesh Bhaskar
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Philosophy, Mathematics and Science Section.
    Fine structure of K-absorption limit of silicon oxide1930In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 125, p. 777-778Article in journal (Refereed)
    Abstract [en]

    THAT the X-ray absorption limits are not simple but show a rather complicated structure has been known now for some time. The main difficulties in their experimental investigation are in respect of (1) amount of the absorbing substance, and (2) dispersion of the spectrograph. The amount of the absorber must not be either too great or too small, otherwise the details are lost. Secondly, the dispersion must be made as large as possible to bring out all the details and measure them with the usual accuracy.

  • 128. Dethoff, Elizabeth A
    et al.
    Petzold, Katja
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Chugh, Jeetender
    Casiano-Negroni, Anette
    Al-Hashimi, Hashim M
    Visualizing transient low-populated structures of RNA2012In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 491, no 7426, p. 724-728Article in journal (Refereed)
    Abstract [en]

    The visualization of RNA conformational changes has provided fundamental insights into how regulatory RNAs carry out their biological functions. The RNA structural transitions that have been characterized so far involve long-lived species that can be captured by structure characterization techniques. Here we report the nuclear magnetic resonance visualization of RNA transitions towards 'invisible' excited states (ESs), which exist in too little abundance (2-13%) and for too short a duration (45-250 μs) to allow structural characterization by conventional techniques. Transitions towards ESs result in localized rearrangements in base-pairing that alter building block elements of RNA architecture, including helix-junction-helix motifs and apical loops. The ES can inhibit function by sequestering residues involved in recognition and signalling or promote ATP-independent strand exchange. Thus, RNAs do not adopt a single conformation, but rather exist in rapid equilibrium with alternative ESs, which can be stabilized by cellular cues to affect functional outcomes.

  • 129. Ding, Li
    et al.
    Getz, Gad
    Wheeler, David A
    Mardis, Elaine R
    McLellan, Michael D
    Cibulskis, Kristian
    Sougnez, Carrie
    Greulich, Heidi
    Muzny, Donna M
    Morgan, Margaret B
    Fulton, Lucinda
    Fulton, Robert S
    Zhang, Qunyuan
    Wendl, Michael C
    Lawrence, Michael S
    Larson, David E
    Chen, Ken
    Dooling, David J
    Sabo, Aniko
    Hawes, Alicia C
    Shen, Hua
    Jhangiani, Shalini N
    Lewis, Lora R
    Hall, Otis
    Zhu, Yiming
    Mathew, Tittu
    Ren, Yanru
    Yao, Jiqiang
    Scherer, Steven E
    Clerc, Kerstin
    Metcalf, Ginger A
    Ng, Brian
    Milosavljevic, Aleksandar
    Gonzalez-Garay, Manuel L
    Osborne, John R
    Meyer, Rick
    Shi, Xiaoqi
    Tang, Yuzhu
    Koboldt, Daniel C
    Lin, Ling
    Abbott, Rachel
    Miner, Tracie L
    Pohl, Craig
    Fewell, Ginger
    Haipek, Carrie
    Schmidt, Heather
    Dunford-Shore, Brian H
    Kraja, Aldi
    Crosby, Seth D
    Sawyer, Christopher S
    Vickery, Tammi
    Sander, Sacha
    Robinson, Jody
    Winckler, Wendy
    Baldwin, Jennifer
    Chirieac, Lucian R
    Dutt, Amit
    Fennell, Tim
    Hanna, Megan
    Johnson, Bruce E
    Onofrio, Robert C
    Thomas, Roman K
    Tonon, Giovanni
    Weir, Barbara A
    Zhao, Xiaojun
    Ziaugra, Liuda
    Zody, Michael C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Giordano, Thomas
    Orringer, Mark B
    Roth, Jack A
    Spitz, Margaret R
    Wistuba, Ignacio I
    Ozenberger, Bradley
    Good, Peter J
    Chang, Andrew C
    Beer, David G
    Watson, Mark A
    Ladanyi, Marc
    Broderick, Stephen
    Yoshizawa, Akihiko
    Travis, William D
    Pao, William
    Province, Michael A
    Weinstock, George M
    Varmus, Harold E
    Gabriel, Stacey B
    Lander, Eric S
    Gibbs, Richard A
    Meyerson, Matthew
    Wilson, Richard K
    Somatic mutations affect key pathways in lung adenocarcinoma2008In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 455, no 7216, p. 1069-1075Article in journal (Refereed)
    Abstract [en]

    Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well-classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are probably involved in carcinogenesis. The frequently mutated genes include tyrosine kinases, among them the EGFR homologue ERBB4; multiple ephrin receptor genes, notably EPHA3; vascular endothelial growth factor receptor KDR; and NTRK genes. These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers--including NF1, APC, RB1 and ATM--and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. The observed mutational profiles correlate with clinical features, smoking status and DNA repair defects. These results are reinforced by data integration including single nucleotide polymorphism array and gene expression array. Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment.

  • 130.
    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.

  • 131.
    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.

  • 132.
    Dubrovinsky, L.
    et al.
    Bayerisches Geoinstitut, Universität Bayreuth.
    Dubrovinskaia, N.
    Bayerisches Geoinstitut, Universität Bayreuth.
    Langenhorst, F.
    Bayerisches Geoinstitut, Universität Bayreuth.
    Dobson, D.
    Bayerisches Geoinstitut, Universität Bayreuth.
    Rubie, D.
    Bayerisches Geoinstitut, Universität Bayreuth.
    Gessgmann, C.
    Max-Planck-Institut für Chemie, Mainz.
    Abrikosov, I. A.
    Condensed Matter Theory Group, Department of Physics, Uppsala University.
    Johansson, Börje
    KTH, Superseded Departments, Materials Science and Engineering.
    Baykov, Vitaly
    KTH, Superseded Departments, Materials Science and Engineering.
    Vitos, Levente
    KTH, Superseded Departments, Materials Science and Engineering.
    Le Bihan, T.
    European Synchrotron Radiation Facility, Grenoble.
    Crichton, W. A.
    European Synchrotron Radiation Facility, Grenoble.
    Dmitriev, V.
    Swiss-Norwegian Beam Lines at ESRF, Grenoble.
    Weber, H. P.
    Swiss-Norwegian Beam Lines at ESRF, Grenoble.
    Iron-silica interaction at extreme conditions and the electrically conducting layer at the base of Earth's mantle2003In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 422, no 6927, p. 58-61Article in journal (Refereed)
    Abstract [en]

    The boundary between the Earth's metallic core and its silicate mantle is characterized by strong lateral heterogeneity and sharp changes in density, seismic wave velocities, electrical conductivity and chemical composition(1-7). To investigate the composition and properties of the lowermost mantle, an understanding of the chemical reactions that take place between liquid iron and the complex Mg-Fe-Si-Al-oxides of the Earth's lower mantle is first required(8-15). Here we present a study of the interaction between iron and silica (SiO2) in electrically and laser-heated diamond anvil cells. In a multianvil apparatus at pressures up to 140 GPa and temperatures over 3,800 K we simulate conditions down to the core-mantle boundary. At high temperature and pressures below 40 GPa, iron and silica react to form iron oxide and an iron-silicon alloy, with up to 5 wt% silicon. At pressures of 85-140 GPa, however, iron and SiO2 do not react and iron-silicon alloys dissociate into almost pure iron and a CsCl-structured (B2) FeSi compound. Our experiments suggest that a metallic silicon-rich B2 phase, produced at the core-mantle boundary (owing to reactions between iron and silicate(2,9,10,13)), could accumulate at the boundary between the mantle and core and explain the anomalously high electrical conductivity of this region(6).

  • 133. Dubrovinsky, L. S.
    et al.
    Dubrovinskaia, N. A.
    Swamy, V.
    Muscat, J.
    Harrison, N. M.
    Ahuja, Rajeev
    Holm, B.
    Johansson, Börje
    KTH, Superseded Departments, Materials Science and Engineering.
    Materials science - The hardest known oxide2001In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 410, no 6829, p. 653-654Article in journal (Refereed)
  • 134. Dujon, B
    et al.
    Albermann, K
    Aldea, M
    Alexandraki, D
    Ansorge, W
    Arino, J
    Benes, V
    Bohn, C
    BolotinFukuhara, M
    Bordonne, R
    Boyer, J
    Camasses, A
    Casamayor, A
    Casas, C
    Cheret, G
    Cziepluch, C
    DaignanFornier, B
    Dang, V
    deHaan, M
    Delius, H
    Durand, P
    Fairhead, C
    Feldmann, H
    Gaillon, L
    Galisson, F
    Gamo, J
    Gancedo, C
    Goffeau, A
    Goulding, E
    Grivell, A
    Habbig, B
    Hand, J
    Hani, J
    Hattenhorst, U
    Hebling, U
    Hernando, Y
    Herrero, E
    Heumann, K
    Hiesel, R
    Hilger, F
    Hofmann, B
    Hollenberg, P
    Hughes, B
    Jauniaux, C
    Kalogeropoulos, A
    Katsoulou, C
    Kordes, E
    Lafuente, J
    Landt, O
    Louis, J
    Maarse, C
    Madania, A
    Mannhaupt, G
    Marck, C
    Martin, P
    Mewes, W
    Michaux, G
    Paces, V
    ParleMcDermott, G
    Pearson, M
    Perrin, A
    Pettersson, B
    Poch, O
    Pohl, M
    Poirey, R
    Portetelle, D
    Pujol, A
    Purnelle, B
    Rad, R
    Rechmann, S
    Schwager, C
    Schweizer, M
    Sor, F
    Sterky, Fredrik
    KTH, Superseded Departments, Biotechnology.
    Tarassov, A
    Teodoru, C
    Tettelin, H
    Thierry, A
    Tobiasch, E
    Tzermia, M
    Uhlen, Mathias
    KTH, Superseded Departments, Biotechnology.
    Unseld, M
    Valens, M
    Vandenbol, M
    Vetter, I
    Vicek, C
    Voet, M
    Volckaert, G
    Voss, H
    Wambutt, R
    Wedler, H
    Wiemann, S
    Winsor, B
    Wolfe, H
    Zollner, A
    Zumstein, E
    Kleine, K
    The nucleotide sequence of Saccharomyces cerevisiae chromosome XV1997In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 387, no 6632, p. 98-102Article in journal (Refereed)
    Abstract [en]

    Chromosome XV was one of the last two chromosomes of Saccharomyces cerevisiae to be discovered(1). It is the third-largest yeast chromosome after chromosomes XII and IV, and is very similar in size to chromosome VII. It alone represents 9% of the yeast genome (8% if ribosomal DNA is included). When systematic sequencing of chromosome XV was started, 93 genes or markers were identified, and most of them were mapped(2). However, very little else was known about chromosome XV which, in contrast to shorter chromosomes, had not been the object of comprehensive genetic or molecular analysis. It was therefore decided to start sequencing chromosome XV only in the third phase of the European Yeast Genome Sequencing Programme, after experience was gained on chromosomes III, XI and II (refs 3-5). The sequence of chromosome XV has been determined from a set of partly overlapping cosmid clones derived from a unique yeast strain, and physically mapped at 3.3-kilobase resolution before sequencing. As well as numerous new open reading frames (ORFs) and genes encoding tRNA or small RNA molecules, the sequence of 1,091,283 base pairs confirms the high proportion of orphan genes and reveals a number of ancestral and successive duplications with other yeast chromosomes.

  • 135.
    Dupret, Vincent
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
    Sanchez, Sophie
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
    Goujet, Daniel
    Tafforeau, Paul
    Ahlberg, Per Erik
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
    A primitive placoderm sheds light on the origin of the jawed vertebrate face2014In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 507, no 7493, p. 500-503Article in journal (Refereed)
    Abstract [en]

    Extant vertebrates form two clades, the jawless Cyclostomata (lampreys and hagfishes) and the jawed Gnathostomata (all other vertebrates), with contrasting facial architectures(1,2). These arise during development from just a few key differences in the growth patterns of the cranial primordia: notably, the nasal sacs and hypophysis originate from a single placode in cyclostomes but from separate placodes in gnathostomes, and infraoptic ectomesenchyme migrates forward either side of the single placode in cyclostomes but between the placodes in gnathostomes(3-8). Fossil stem gnathostomes preserve cranial anatomies rich in landmarks that provide proxies for developmental processes and allow the transition from jawless to jawed vertebrates to be broken down into evolutionary steps(7,9-12). Here we use propagation phase contrast synchrotron microtomography to image the cranial anatomy of the primitive placoderm (jawed stem gnathostome) Romundina(13), and show that itcombines jawed vertebrate architecture with cranial and cerebral proportions resembling those of cyclostomes and the galeaspid (jawless stem gnathostome) Shuyu(11). This combination seems to be primitive for jawed vertebrates, and suggests a decoupling between ectomesenchymal growth trajectory, ectomesenchymal proliferation, and cerebral shape change during the origin of gnathostomes.

  • 136. Edgar, Graham J.
    et al.
    Stuart-Smith, Rick D.
    Willis, Trevor J.
    Kininmonth, Stuart
    Stockholm University, Faculty of Science, Stockholm Resilience Centre. University of Tasmania, Australia.
    Baker, Susan C.
    Banks, Stuart
    Barrett, Neville S.
    Becerro, Mikel A.
    Bernard, Anthony T. F.
    Berkhout, Just
    Buxton, Colin D.
    Campbell, Stuart J.
    Cooper, Antonia T.
    Davey, Marlene
    Edgar, Sophie C.
    Foersterra, Guenter
    Galvan, David E.
    Irigoyen, Alejo J.
    Kushner, David J.
    Moura, Rodrigo
    Parnell, P. Ed
    Shears, Nick T.
    Soler, German
    Strain, Elisabeth M. A.
    Thomson, Russell J.
    Global conservation outcomes depend on marine protected areas with five key features2014In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 506, no 7487, p. 216-+Article in journal (Refereed)
    Abstract [en]

    In line with global targets agreed under the Convention on Biological Diversity, the number of marine protected areas (MPAs) is increasing rapidly, yet socio-economic benefits generated by MPAs remain difficult to predict and under debate(1,2). MPAs often fail to reach their full potential as a consequence of factors such as illegal harvesting, regulations that legally allow detrimental harvesting, or emigration of animals outside boundaries because of continuous habitat or inadequate size of reserve(3-5). Here we show that the conservation benefits of 87 MPAs investigated worldwide increase exponentially with the accumulation of five key features: no take, well enforced, old (>10 years), large (>100 km(2)), and isolated by deep water or sand. Using effective MPAs with four or five key features as an unfished standard, comparisons of underwater survey data from effective MPAs with predictions based on survey data from fished coasts indicate that total fish biomass has declined about two-thirds from historical baselines as a result of fishing. Effective MPAs also had twice as many large (>250 mm total length) fish species per transect, five times more large fish biomass, and fourteen times more shark biomass than fished areas. Most (59%) of the MPAs studied had only one or two key features and were not ecologically distinguishable from fished sites. Our results show that global conservation targets based on area alone will not optimize protection of marine biodiversity. More emphasis is needed on better MPA design, durable management and compliance to ensure that MPAs achieve their desired conservation value.

  • 137. Eghbali, M
    et al.
    Curmi, J P
    Birnir, Bryndis
    John Curtin School of Medical Research, Australian National University.
    Gage, P W
    Hippocampal GABA(A) channel conductance increased by diazepam.1997In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 388, no 6637, p. 71-5Article in journal (Refereed)
    Abstract [en]

    Benzodiazepines, which are widely used clinically for relief of anxiety and for sedation, are thought to enhance synaptic inhibition in the central nervous system by increasing the open probability of chloride channels activated by the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Here we show that the benzodiazepine diazepam can also increase the conductance of GABAA channels activated by low concentrations of GABA (0.5 or 5 microM) in rat cultured hippocampal neurons. Before exposure to diazepam, chloride channels activated by GABA had conductances of 8 to 53pS. Diazepam caused a concentration-dependent and reversible increase in the conductance of these channels towards a maximum conductance of 70-80 pS and the effect was as great as 7-fold in channels of lowest initial conductance. Increasing the conductance of GABAA channels tonically activated by low ambient concentrations of GABA in the extracellular environment may be an important way in which these drugs depress excitation in the central nervous system. That any drug has such a large effect on single channel conductance has not been reported previously and has implications for models of channel structure and conductance.

  • 138. Egorov, A. V.
    et al.
    Hamam, B. N.
    Fransén, Erik
    KTH, Superseded Departments, Numerical Analysis and Computer Science, NADA.
    Hasselmo, M. E.
    Alonso, A. A.
    Graded persistent activity in entorhinal cortex neurons2002In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 420, no 6912, p. 173-178Article in journal (Refereed)
    Abstract [en]

    Working memory represents the ability of the brain to hold externally or internally driven information for relatively short periods of time(1,2). Persistent neuronal activity is the elementary process underlying working memory but its cellular basis remains unknown. The most widely accepted hypothesis is that persistent activity is based on synaptic reverberations in recurrent circuits. The entorhinal cortex in the parahippocampal region is crucially involved in the acquisition, consolidation and retrieval of long-term memory traces for which working memory operations are essential(2). Here we show that individual neurons from layer V of the entorhinal cortex-which link the hippocampus to extensive cortical regions(3)-respond to consecutive stimuli with graded changes in firing frequency that remain stable after each stimulus presentation. In addition, the sustained levels of firing frequency can be either increased or decreased in an input-specific manner. This firing behaviour displays robustness to distractors; it is linked to cholinergic muscarinic receptor activation, and relies on activity-dependent changes of a Ca2+-sensitive cationic current. Such an intrinsic neuronal ability to generate graded persistent activity constitutes an elementary mechanism for working memory.

  • 139.
    Ehrenberg, Måns
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Structure and Molecular Biology.
    Protein synthesis: Translocation in slow motion2010In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 466, no 7304, p. 325-326Article in journal (Refereed)
  • 140. Ehret, Georg B.
    et al.
    Munroe, Patricia B.
    Rice, Kenneth M.
    Bochud, Murielle
    Johnson, Andrew D.
    Chasman, Daniel I.
    Smith, Albert V.
    Tobin, Martin D.
    Verwoert, Germaine C.
    Hwang, Shih-Jen
    Pihur, Vasyl
    Vollenweider, Peter
    O'Reilly, Paul F.
    Amin, Najaf
    Bragg-Gresham, Jennifer L.
    Teumer, Alexander
    Glazer, Nicole L.
    Launer, Lenore
    Zhao, Jing Hua
    Aulchenko, Yurii
    Heath, Simon
    Sober, Siim
    Parsa, Afshin
    Luan, Jian'an
    Arora, Pankaj
    Dehghan, Abbas
    Zhang, Feng
    Lucas, Gavin
    Hicks, Andrew A.
    Jackson, Anne U.
    Peden, John F.
    Tanaka, Toshiko
    Wild, Sarah H.
    Rudan, Igor
    Igl, Wilmar
    Milaneschi, Yuri
    Parker, Alex N.
    Fava, Cristiano
    Chambers, John C.
    Fox, Ervin R.
    Kumari, Meena
    Go, Min Jin
    van der Harst, Pim
    Kao, Wen Hong Linda
    Sjogren, Marketa
    Vinay, D. G.
    Alexander, Myriam
    Tabara, Yasuharu
    Shaw-Hawkins, Sue
    Whincup, Peter H.
    Liu, Yongmei
    Shi, Gang
    Kuusisto, Johanna
    Tayo, Bamidele
    Seielstad, Mark
    Sim, Xueling
    Nguyen, Khanh-Dung Hoang
    Lehtimaki, Terho
    Matullo, Giuseppe
    Wu, Ying
    Gaunt, Tom R.
    Onland-Moret, N. Charlotte
    Cooper, Matthew N.
    Platou, Carl G. P.
    Org, Elin
    Hardy, Rebecca
    Dahgam, Santosh
    Palmen, Jutta
    Vitart, Veronique
    Braund, Peter S.
    Kuznetsova, Tatiana
    Uiterwaal, Cuno S. P. M.
    Adeyemo, Adebowale
    Palmas, Walter
    Campbell, Harry
    Ludwig, Barbara
    Tomaszewski, Maciej
    Tzoulaki, Ioanna
    Palmer, Nicholette D.
    Aspelund, Thor
    Garcia, Melissa
    Chang, Yen-Pei C.
    O'Connell, Jeffrey R.
    Steinle, Nanette I.
    Grobbee, Diederick E.
    Arking, Dan E.
    Kardia, Sharon L.
    Morrison, Alanna C.
    Hernandez, Dena
    Najjar, Samer
    McArdle, Wendy L.
    Hadley, David
    Brown, Morris J.
    Connell, John M.
    Hingorani, Aroon D.
    Day, Ian N. M.
    Lawlor, Debbie A.
    Beilby, John P.
    Lawrence, Robert W.
    Clarke, Robert
    Hopewell, Jemma C.
    Ongen, Halit
    Dreisbach, Albert W.
    Li, Yali
    Young, J. Hunter
    Bis, Joshua C.
    Kahonen, Mika
    Viikari, Jorma
    Adair, Linda S.
    Lee, Nanette R.
    Chen, Ming-Huei
    Olden, Matthias
    Pattaro, Cristian
    Bolton, Judith A. Hoffman
    Koettgen, Anna
    Bergmann, Sven
    Mooser, Vincent
    Chaturvedi, Nish
    Frayling, Timothy M.
    Islam, Muhammad
    Jafar, Tazeen H.
    Erdmann, Jeanette
    Kulkarni, Smita R.
    Bornstein, Stefan R.
    Graessler, Juergen
    Groop, Leif
    Voight, Benjamin F.
    Kettunen, Johannes
    Howard, Philip
    Taylor, Andrew
    Guarrera, Simonetta
    Ricceri, Fulvio
    Emilsson, Valur
    Plump, Andrew
    Barroso, Ine S.
    Khaw, Kay-Tee
    Weder, Alan B.
    Hunt, Steven C.
    Sun, Yan V.
    Bergman, Richard N.
    Collins, Francis S.
    Bonnycastle, Lori L.
    Scott, Laura J.
    Stringham, Heather M.
    Peltonen, Leena
    Perola, Markus
    Vartiainen, Erkki
    Brand, Stefan-Martin
    Staessen, Jan A.
    Wang, Thomas J.
    Burton, Paul R.
    Artigas, Maria Soler
    Dong, Yanbin
    Snieder, Harold
    Wang, Xiaoling
    Zhu, Haidong
    Lohman, Kurt K.
    Rudock, Megan E.
    Heckbert, Susan R.
    Smith, Nicholas L.
    Wiggins, Kerri L.
    Doumatey, Ayo
    Shriner, Daniel
    Veldre, Gudrun
    Viigimaa, Margus
    Kinra, Sanjay
    Prabhakaran, Dorairaj
    Tripathy, Vikal
    Langefeld, Carl D.
    Rosengren, Annika
    Thelle, Dag S.
    Corsi, Anna Maria
    Singleton, Andrew
    Forrester, Terrence
    Hilton, Gina
    McKenzie, Colin A.
    Salako, Tunde
    Iwai, Naoharu
    Kita, Yoshikuni
    Ogihara, Toshio
    Ohkubo, Takayoshi
    Okamura, Tomonori
    Ueshima, Hirotsugu
    Umemura, Satoshi
    Eyheramendy, Susana
    Meitinger, Thomas
    Wichmann, H. -Erich
    Cho, Yoon Shin
    Kim, Hyung-Lae
    Lee, Jong-Young
    Scott, James
    Sehmi, Joban S.
    Zhang, Weihua
    Hedblad, Bo
    Nilsson, Peter
    Smith, George Davey
    Wong, Andrew
    Narisu, Narisu
    Stancakova, Alena
    Raffel, Leslie J.
    Yao, Jie
    Kathiresan, Sekar
    O'Donnell, Christopher J.
    Schwartz, Stephen M.
    Ikram, M. Arfan
    Longstreth, W. T., Jr.
    Mosley, Thomas H.
    Seshadri, Sudha
    Shrine, Nick R. G.
    Wain, Louise V.
    Morken, Mario A.
    Swift, Amy J.
    Laitinen, Jaana
    Prokopenko, Inga
    Zitting, Paavo
    Cooper, Jackie A.
    Humphries, Steve E.
    Danesh, John
    Rasheed, Asif
    Goel, Anuj
    Hamsten, Anders
    Watkins, Hugh
    Bakker, Stephan J. L.
    van Gilst, Wiek H.
    Janipalli, Charles S.
    Mani, K. Radha
    Yajnik, Chittaranjan S.
    Hofman, Albert
    Mattace-Raso, Francesco U. S.
    Oostra, Ben A.
    Demirkan, Ayse
    Isaacs, Aaron
    Rivadeneira, Fernando
    Lakatta, Edward G.
    Orru, Marco
    Scuteri, Angelo
    Ala-Korpela, Mika
    Kangas, Antti J.
    Lyytikainen, Leo-Pekka
    Soininen, Pasi
    Tukiainen, Taru
    Wurtz, Peter
    Ong, Rick Twee-Hee
    Doerr, Marcus
    Kroemer, Heyo K.
    Voelker, Uwe
    Voelzke, Henry
    Galan, Pilar
    Hercberg, Serge
    Lathrop, Mark
    Zelenika, Diana
    Deloukas, Panos
    Mangino, Massimo
    Spector, Tim D.
    Zhai, Guangju
    Meschia, James F.
    Nalls, Michael A.
    Sharma, Pankaj
    Terzic, Janos
    Kumar, M. V. Kranthi
    Denniff, Matthew
    Zukowska-Szczechowska, Ewa
    Wagenknecht, Lynne E.
    Fowkes, F. Gerald R.
    Charchar, Fadi J.
    Schwarz, Peter E. H.
    Hayward, Caroline
    Guo, Xiuqing
    Rotimi, Charles
    Bots, Michiel L.
    Brand, Eva
    Samani, Nilesh J.
    Polasek, Ozren
    Talmud, Philippa J.
    Nyberg, Fredrik
    Kuh, Diana
    Laan, Maris
    Hveem, Kristian
    Palmer, Lyle J.
    van der Schouw, Yvonne T.
    Casas, Juan P.
    Mohlke, Karen L.
    Vineis, Paolo
    Raitakari, Olli
    Ganesh, Santhi K.
    Wong, Tien Y.
    Tai, E. Shyong
    Cooper, Richard S.
    Laakso, Markku
    Rao, Dabeeru C.
    Harris, Tamara B.
    Morris, Richard W.
    Dominiczak, Anna F.
    Kivimaki, Mika
    Marmot, Michael G.
    Miki, Tetsuro
    Saleheen, Danish
    Chandak, Giriraj R.
    Coresh, Josef
    Navis, Gerjan
    Salomaa, Veikko
    Han, Bok-Ghee
    Zhu, Xiaofeng
    Kooner, Jaspal S.
    Melander, Olle
    Ridker, Paul M.
    Bandinelli, Stefania
    Gyllensten, Ulf B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Wright, Alan F.
    Wilson, James F.
    Ferrucci, Luigi
    Farrall, Martin
    Tuomilehto, Jaakko
    Pramstaller, Peter P.
    Elosua, Roberto
    Soranzo, Nicole
    Sijbrands, Eric J. G.
    Altshuler, David
    Loos, Ruth J. F.
    Shuldiner, Alan R.
    Gieger, Christian
    Meneton, Pierre
    Uitterlinden, Andre G.
    Wareham, Nicholas J.
    Gudnason, Vilmundur
    Rotter, Jerome I.
    Rettig, Rainer
    Uda, Manuela
    Strachan, David P.
    Witteman, Jacqueline C. M.
    Hartikainen, Anna-Liisa
    Beckmann, Jacques S.
    Boerwinkle, Eric
    Vasan, Ramachandran S.
    Boehnke, Michael
    Larson, Martin G.
    Jarvelin, Marjo-Riitta
    Psaty, Bruce M.
    Abecasis, Goncalo R.
    Chakravarti, Aravinda
    Elliott, Paul
    van Duijn, Cornelia M.
    Newton-Cheh, Christopher
    Levy, Daniel
    Caulfield, Mark J.
    Johnson, Toby
    Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk2011In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 478, no 7367, p. 103-109Article in journal (Refereed)
    Abstract [en]

    Blood pressure is a heritable trait(1) influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (>= 140 mm Hg systolic blood pressure or >= 90 mm Hg diastolic blood pressure)(2). Even small increments in blood pressure are associated with an increased risk of cardiovascular events(3). This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.

  • 141.
    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.

  • 142. El Albani, Abderrazak
    et al.
    Bengtson, Stefan
    Canfield, Donald E.
    Bekker, Andrey
    Macchiarelli, Roberto
    Mazurier, Arnaud
    Hammarlund, Emma U.
    Stockholm University, Faculty of Science, Department of Geological Sciences.
    Boulvais, Philippe
    Dupuy, Jean-Jacques
    Fontaine, Claude
    Fuersich, Franz T.
    Gauthier-Lafaye, Francois
    Janvier, Philippe
    Javaux, Emmanuelle
    Ossa, Frantz Ossa
    Pierson-Wickmann, Anne-Catherine
    Riboulleau, Armelle
    Sardini, Paul
    Vachard, Daniel
    Whitehouse, Martin
    Meunier, Alain
    Large colonial organisms with coordinated growth in oxygenated environments 2.1 Gyr ago2010In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 466, no 7302, p. 100-104Article in journal (Refereed)
    Abstract [en]

    The evidence for macroscopic life during the Palaeoproterozoic era (2.5-1.6 Gyr ago) is controversial(1-5). Except for the nearly 2-Gyr-old coil-shaped fossil Grypania spiralis(6,7), which may have been eukaryotic, evidence for morphological and taxonomic bio-diversification of macroorganisms only occurs towards the beginning of the Mesoproterozoic era (1.6-1.0 Gyr)(8). Here we report the discovery of centimetre-sized structures from the 2.1-Gyr-old black shales of the Palaeoproterozoic Francevillian B Formation in Gabon, which we interpret as highly organized and spatially discrete populations of colonial organisms. The structures are up to 12 cm in size and have characteristic shapes, with a simple but distinct ground pattern of flexible sheets and, usually, a permeating radial fabric. Geochemical analyses suggest that the sediments were deposited under an oxygenated water column. Carbon and sulphur isotopic data indicate that the structures were distinct biogenic objects, fossilized by pyritization early in the formation of the rock. The growth patterns deduced from the fossil morphologies suggest that the organisms showed cell-to-cell signalling and coordinated responses, as is commonly associated with multicellular organization(9). The Gabon fossils, occurring after the 2.45-2.32-Gyr increase in atmospheric oxygen concentration(10), may be seen as ancient representatives of multicellular life, which expanded so rapidly 1.5 Gyr later, in the Cambrian explosion.

  • 143.
    Ellegren, Hans
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Evolutionary Biology.
    Sheldon, Ben C.
    Genetic basis of fitness differences in natural populations2008In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 452, no 7184, p. 169-175Article, review/survey (Refereed)
    Abstract [en]

    Genomics profoundly influences current biology. One of many exciting consequences of this revolution is the potential for identifying and studying the genetic basis of those traits affecting fitness that are key to natural selection. Recent studies using a multitude of genomic approaches have established such genotype - phenotype relationships in natural populations, giving new insight into the genetic architecture of quantitative variation. In parallel, an emerging understanding of the quantitative genetics of fitness variation in the wild means that we are poised to see a synthesis of ecological and molecular approaches in evolutionary biology.

  • 144.
    Ellegren, Hans
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Smeds, Linnea
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Burri, Reto
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Ólason, Páll I.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Backström, Niclas
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Kawakami, Takeshi
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Künstner, Axel
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Mäkinen, Hannu
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Nadachowska-Brzyska, Krystyna
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Qvarnström, Anna
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal Ecology.
    Uebbing, Severin
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Wolf, Jochen B. W.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    The genomic landscape of species divergence in Ficedula flycatchers2012In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 491, no 7426, p. 756-760Article in journal (Refereed)
    Abstract [en]

    Unravelling the genomic landscape of divergence between lineages is key to understanding speciation. The naturally hybridizing collared flycatcher and pied flycatcher are important avian speciation models that show pre-as well as postzygotic isolation. We sequenced and assembled the 1.1-Gb flycatcher genome, physically mapped the assembly to chromosomes using a low-density linkage map and re-sequenced population samples of each species. Here we show that the genomic landscape of species differentiation is highly heterogeneous with approximately 50 'divergence islands' showing up to 50-fold higher sequence divergence than the genomic background. These non-randomly distributed islands, with between one and three regions of elevated divergence per chromosome irrespective of chromosome size, are characterized by reduced levels of nucleotide diversity, skewed allele-frequency spectra, elevated levels of linkage disequilibrium and reduced proportions of shared polymorphisms in both species, indicative of parallel episodes of selection. Proximity of divergence peaks to genomic regions resistant to sequence assembly, potentially including centromeres and telomeres, indicate that complex repeat structures may drive species divergence. A much higher background level of species divergence of the Z chromosome, and a lower proportion of shared polymorphisms, indicate that sex chromosomes and autosomes are at different stages of speciation. This study provides a roadmap to the emerging field of speciation genomics.

  • 145.
    Elmgren, Ragnar
    et al.
    Stockholm University, Faculty of Science, Department of Systems Ecology.
    Kumblad, Linda
    Stockholm University, Faculty of Science, Department of Systems Ecology.
    Emil, Rydin
    Baltic2020 Foundation.
    Wulff, Fredrik V.
    Stockholm University, Faculty of Science, Department of Systems Ecology.
    Political backing to save the Baltic sea2012In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 487, p. 432-432Article in journal (Other (popular science, discussion, etc.))
  • 146.
    Elming, Sten-åke
    Luleå University of Technology, Department of Civil, Environmental and Natural Resources Engineering, Geosciences and Environmental Engineering.
    Evidence for early Proterozoic plate tectonics from seismic reflection profiles in the Baltic Shield1990In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 348, p. 34-38Article in journal (Refereed)
    Abstract [en]

    Plate tectonics provides the linking framework for all tectonic and magmatic activity seen today, but it is not known when plate tectonics first developed on Earth. New deep seismic reflection and coincident refraction profiles across an exposed, 1.89-Gyr-old volcanic arc complex show a 10-km-thick offset in the Moho and bivergent reflectors in the crust, which were most probably created by plate convergence, subduction and accretion during the Early Proterozoic. Hence, plate tectonic models seem to be applicable for at least the second half of Earth's history.

  • 147.
    Elmqvist, Thomas
    Stockholm University, Faculty of Science, Stockholm Resilience Centre.
    Sustainability and resilience differ2017In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 546, no 7658, p. 352-352Article in journal (Other academic)
  • 148.
    Emerson, B. C.
    et al.
    University of East Anglia, UK.
    Kolm, Niclas
    University of East Anglia, UK; University of Edinburgh, UK.
    Ecology: Is speciation driven by species diversity? Reply.2005In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 438, no 7064, p. E2-Article in journal (Refereed)
  • 149.
    Emerson, B. C.
    et al.
    University of East Anglia, UK.
    Kolm, Niclas
    University of East Anglia, UK; University of Edinburgh, UK.
    Species diversity can drive speciation2005In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 434, no 7036, p. 1015-1017Article in journal (Refereed)
    Abstract [en]

    A fundamental question in evolutionary ecology and conservation biology is: why do some areas contain greater species diversity than others? Island biogeographic theory has identified the roles of immigration and extinction in relation to area size and proximity to source areas(1,2), and the role of speciation is also recognized as an important factor(3-6). However, one as yet unexplored possibility is that species diversity itself might help to promote speciation, and indeed the central tenets of island biogeographic theory support such a prediction. Here we use data for plants and arthropods of the volcanic archipelagos of the Canary and Hawaiian Islands to address whether there is a positive relationship between species diversity and rate of diversification. Our index of diversification for each island is the proportion of species that are endemic, and we test our prediction that this increases with increasing species number. We show that even after controlling for several important physical features of islands, diversification is strongly related to species number.

  • 150. Englund, Camilla
    et al.
    Loren, Christina
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Pathogenesis (UCMP) (Faculty of Medicine).
    Grabbe, Caroline
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Pathogenesis (UCMP) (Faculty of Medicine).
    Varshney, Gaurav
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Pathogenesis (UCMP) (Faculty of Medicine).
    Deleuil, Fabiene
    Hallberg, Bengt
    Palmer, Ruth
    Jeb signals through the Alk receptor tyrosine kinase to drive visceral muscle fusion2003In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 425, no 6957, p. 512-516Article in journal (Refereed)
1234567 101 - 150 of 480
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