Change search
Refine search result
2345678 201 - 250 of 451
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the 'Create feeds' function.
  • 201.
    Josefsson, Agnetha M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Magnusson, Partik K. E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Ylitalo, Nathalie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Quarforth-Tubbin, Pernilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Pontén, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Adami, Hans-Olov
    Gyllensten, Ulf B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    p53 polymorphism and risk of cervical cancer1998In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 396, no 6711, 531- p.Article in journal (Refereed)
  • 202. Joshi, Peter K
    et al.
    Esko, Tonu
    Mattsson, Hannele
    Eklund, Niina
    Gandin, Ilaria
    Nutile, Teresa
    Jackson, Anne U
    Schurmann, Claudia
    Smith, Albert V
    Zhang, Weihua
    Okada, Yukinori
    Stančáková, Alena
    Faul, Jessica D
    Zhao, Wei
    Bartz, Traci M
    Concas, Maria Pina
    Franceschini, Nora
    Enroth, Stefan
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Vitart, Veronique
    Trompet, Stella
    Guo, Xiuqing
    Chasman, Daniel I
    O'Connel, Jeffrey R
    Corre, Tanguy
    Nongmaithem, Suraj S
    Chen, Yuning
    Mangino, Massimo
    Ruggiero, Daniela
    Traglia, Michela
    Farmaki, Aliki-Eleni
    Kacprowski, Tim
    Bjonnes, Andrew
    van der Spek, Ashley
    Wu, Ying
    Giri, Anil K
    Yanek, Lisa R
    Wang, Lihua
    Hofer, Edith
    Rietveld, Cornelius A
    McLeod, Olga
    Cornelis, Marilyn C
    Pattaro, Cristian
    Verweij, Niek
    Baumbach, Clemens
    Abdellaoui, Abdel
    Warren, Helen R
    Vuckovic, Dragana
    Mei, Hao
    Bouchard, Claude
    Perry, John R B
    Cappellani, Stefania
    Mirza, Saira S
    Benton, Miles C
    Broeckel, Ulrich
    Medland, Sarah E
    Lind, Penelope A
    Malerba, Giovanni
    Drong, Alexander
    Yengo, Loic
    Bielak, Lawrence F
    Zhi, Degui
    van der Most, Peter J
    Shriner, Daniel
    Mägi, Reedik
    Hemani, Gibran
    Karaderi, Tugce
    Wang, Zhaoming
    Liu, Tian
    Demuth, Ilja
    Zhao, Jing Hua
    Meng, Weihua
    Lataniotis, Lazaros
    van der Laan, Sander W
    Bradfield, Jonathan P
    Wood, Andrew R
    Bonnefond, Amelie
    Ahluwalia, Tarunveer S
    Hall, Leanne M
    Salvi, Erika
    Yazar, Seyhan
    Carstensen, Lisbeth
    de Haan, Hugoline G
    Abney, Mark
    Afzal, Uzma
    Allison, Matthew A
    Amin, Najaf
    Asselbergs, Folkert W
    Bakker, Stephan J L
    Barr, R Graham
    Baumeister, Sebastian E
    Benjamin, Daniel J
    Bergmann, Sven
    Boerwinkle, Eric
    Bottinger, Erwin P
    Campbell, Archie
    Chakravarti, Aravinda
    Chan, Yingleong
    Chanock, Stephen J
    Chen, Constance
    Chen, Y-D Ida
    Collins, Francis S
    Connell, John
    Correa, Adolfo
    Cupples, L Adrienne
    Smith, George Davey
    Davies, Gail
    Dörr, Marcus
    Ehret, Georg
    Ellis, Stephen B
    Feenstra, Bjarke
    Feitosa, Mary F
    Ford, Ian
    Fox, Caroline S
    Frayling, Timothy M
    Friedrich, Nele
    Geller, Frank
    Scotland, Generation
    Gillham-Nasenya, Irina
    Gottesman, Omri
    Graff, Misa
    Grodstein, Francine
    Gu, Charles
    Haley, Chris
    Hammond, Christopher J
    Harris, Sarah E
    Harris, Tamara B
    Hastie, Nicholas D
    Heard-Costa, Nancy L
    Heikkilä, Kauko
    Hocking, Lynne J
    Homuth, Georg
    Hottenga, Jouke-Jan
    Huang, Jinyan
    Huffman, Jennifer E
    Hysi, Pirro G
    Ikram, M Arfan
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Joensuu, Anni
    Johansson, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Jousilahti, Pekka
    Jukema, J Wouter
    Kähönen, Mika
    Kamatani, Yoichiro
    Kanoni, Stavroula
    Kerr, Shona M
    Khan, Nazir M
    Koellinger, Philipp
    Koistinen, Heikki A
    Kooner, Manraj K
    Kubo, Michiaki
    Kuusisto, Johanna
    Lahti, Jari
    Launer, Lenore J
    Lea, Rodney A
    Lehne, Benjamin
    Lehtimäki, Terho
    Liewald, David C M
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Loh, Marie
    Lokki, Marja-Liisa
    London, Stephanie J
    Loomis, Stephanie J
    Loukola, Anu
    Lu, Yingchang
    Lumley, Thomas
    Lundqvist, Annamari
    Männistö, Satu
    Marques-Vidal, Pedro
    Masciullo, Corrado
    Matchan, Angela
    Mathias, Rasika A
    Matsuda, Koichi
    Meigs, James B
    Meisinger, Christa
    Meitinger, Thomas
    Menni, Cristina
    Mentch, Frank D
    Mihailov, Evelin
    Milani, Lili
    Montasser, May E
    Montgomery, Grant W
    Morrison, Alanna
    Myers, Richard H
    Nadukuru, Rajiv
    Navarro, Pau
    Nelis, Mari
    Nieminen, Markku S
    Nolte, Ilja M
    O'Connor, George T
    Ogunniyi, Adesola
    Padmanabhan, Sandosh
    Palmas, Walter R
    Pankow, James S
    Patarcic, Inga
    Pavani, Francesca
    Peyser, Patricia A
    Pietilainen, Kirsi
    Poulter, Neil
    Prokopenko, Inga
    Ralhan, Sarju
    Redmond, Paul
    Rich, Stephen S
    Rissanen, Harri
    Robino, Antonietta
    Rose, Lynda M
    Rose, Richard
    Sala, Cinzia
    Salako, Babatunde
    Salomaa, Veikko
    Sarin, Antti-Pekka
    Saxena, Richa
    Schmidt, Helena
    Scott, Laura J
    Scott, William R
    Sennblad, Bengt
    Seshadri, Sudha
    Sever, Peter
    Shrestha, Smeeta
    Smith, Blair H
    Smith, Jennifer A
    Soranzo, Nicole
    Sotoodehnia, Nona
    Southam, Lorraine
    Stanton, Alice V
    Stathopoulou, Maria G
    Strauch, Konstantin
    Strawbridge, Rona J
    Suderman, Matthew J
    Tandon, Nikhil
    Tang, Sian-Tsun
    Taylor, Kent D
    Tayo, Bamidele O
    Töglhofer, Anna Maria
    Tomaszewski, Maciej
    Tšernikova, Natalia
    Tuomilehto, Jaakko
    Uitterlinden, Andre G
    Vaidya, Dhananjay
    van Hylckama Vlieg, Astrid
    van Setten, Jessica
    Vasankari, Tuula
    Vedantam, Sailaja
    Vlachopoulou, Efthymia
    Vozzi, Diego
    Vuoksimaa, Eero
    Waldenberger, Melanie
    Ware, Erin B
    Wentworth-Shields, William
    Whitfield, John B
    Wild, Sarah
    Willemsen, Gonneke
    Yajnik, Chittaranjan S
    Yao, Jie
    Zaza, Gianluigi
    Zhu, Xiaofeng
    Salem, Rany M
    Melbye, Mads
    Bisgaard, Hans
    Samani, Nilesh J
    Cusi, Daniele
    Mackey, David A
    Cooper, Richard S
    Froguel, Philippe
    Pasterkamp, Gerard
    Grant, Struan F A
    Hakonarson, Hakon
    Ferrucci, Luigi
    Scott, Robert A
    Morris, Andrew D
    Palmer, Colin N A
    Dedoussis, George
    Deloukas, Panos
    Bertram, Lars
    Lindenberger, Ulman
    Berndt, Sonja I
    Lindgren, Cecilia M
    Timpson, Nicholas J
    Tönjes, Anke
    Munroe, Patricia B
    Sørensen, Thorkild I A
    Rotimi, Charles N
    Arnett, Donna K
    Oldehinkel, Albertine J
    Kardia, Sharon L R
    Balkau, Beverley
    Gambaro, Giovanni
    Morris, Andrew P
    Eriksson, Johan G
    Wright, Margie J
    Martin, Nicholas G
    Hunt, Steven C
    Starr, John M
    Deary, Ian J
    Griffiths, Lyn R
    Tiemeier, Henning
    Pirastu, Nicola
    Kaprio, Jaakko
    Wareham, Nicholas J
    Pérusse, Louis
    Wilson, James G
    Girotto, Giorgia
    Caulfield, Mark J
    Raitakari, Olli
    Boomsma, Dorret I
    Gieger, Christian
    van der Harst, Pim
    Hicks, Andrew A
    Kraft, Peter
    Sinisalo, Juha
    Knekt, Paul
    Johannesson, Magnus
    Magnusson, Patrik K E
    Hamsten, Anders
    Schmidt, Reinhold
    Borecki, Ingrid B
    Vartiainen, Erkki
    Becker, Diane M
    Bharadwaj, Dwaipayan
    Mohlke, Karen L
    Boehnke, Michael
    van Duijn, Cornelia M
    Sanghera, Dharambir K
    Teumer, Alexander
    Zeggini, Eleftheria
    Metspalu, Andres
    Gasparini, Paolo
    Ulivi, Sheila
    Ober, Carole
    Toniolo, Daniela
    Rudan, Igor
    Porteous, David J
    Ciullo, Marina
    Spector, Tim D
    Hayward, Caroline
    Dupuis, Josée
    Loos, Ruth J F
    Wright, Alan F
    Chandak, Giriraj R
    Vollenweider, Peter
    Shuldiner, Alan R
    Ridker, Paul M
    Rotter, Jerome I
    Sattar, Naveed
    Gyllensten, Ulf
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    North, Kari E
    Pirastu, Mario
    Psaty, Bruce M
    Weir, David R
    Laakso, Markku
    Gudnason, Vilmundur
    Takahashi, Atsushi
    Chambers, John C
    Kooner, Jaspal S
    Strachan, David P
    Campbell, Harry
    Hirschhorn, Joel N
    Perola, Markus
    Polašek, Ozren
    Wilson, James F
    Directional dominance on stature and cognition in diverse human populations2015In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 523, no 7561, 459-462 p.Article in journal (Refereed)
    Abstract [en]

    Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.

  • 203.
    Jostins, Luke
    et al.
    Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
    Halfvarson, Jonas
    Örebro University Hospital. Örebro University, School of Medical Sciences.
    Cho, Judy H.
    Department of Genetics, Yale School of Medicine, New Haven CT, United States; Department of Internal Medicine, Section of Digestive Diseases, Yale School of Medicine, New Haven CT, United States.
    Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease2012In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 491, no 7422, 119-124 p.Article in journal (Refereed)
    Abstract [en]

    Crohn's disease and ulcerative colitis, the two common forms of inflammatory bowel disease (IBD), affect over 2.5 million people of European ancestry, with rising prevalence in other populations(1). Genome-wide association studies and subsequent meta-analyses of these two diseases(2,3) as separate phenotypes have implicated previously unsuspected mechanisms, such as autophagy(4), in their pathogenesis and showed that some IBD loci are shared with other inflammatory diseases(5). Here we expand on the knowledge of relevant pathways by undertaking a meta-analysis of Crohn's disease and ulcerative colitis genome-wide association scans, followed by extensive validation of significant findings, with a combined total of more than 75,000 cases and controls. We identify 71 new associations, for a total of 163 IBD loci, that meet genome-wide significance thresholds. Most loci contribute to both phenotypes, and both directional (consistently favouring one allele over the course of human history) and balancing (favouring the retention of both alleles within populations) selection effects are evident. Many IBD loci are also implicated in other immune-mediated disorders, most notably with ankylosing spondylitis and psoriasis. We also observe considerable overlap between susceptibility loci for IBD and mycobacterial infection. Gene co-expression network analysis emphasizes this relationship, with pathways shared between host responses to mycobacteria and those predisposing to IBD.

  • 204. Jun, C.
    et al.
    Ban, Yifang
    KTH, School of Architecture and the Built Environment (ABE), Urban Planning and Environment, Geoinformatics.
    Li, S.
    Open access to Earth land-cover map2014In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 514, no 7253Article in journal (Refereed)
  • 205. Jun, Chen
    et al.
    Ban, Yifang
    KTH, School of Architecture and the Built Environment (ABE), Urban Planning and Environment, Geodesy and Geoinformatics.
    Li, Songnian
    China: Open access to Earth land-cover map2014In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 514, no 7523, 434-434 p.Article in journal (Refereed)
  • 206.
    Kanopka, Arvydas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Mühleman, Oliver
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Akusjärvi, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Inhibition by SRproteins of splicing of a regulated adenovirus pre-mRNA1996In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 381, 535-538 p.Article in journal (Refereed)
    Abstract [en]

    The adenovirus L1 unit represents an example of an alternatively spliced precursor messenger (pre-mRNA) where on 5' splice can be jointed to one of two alternative 3' splice sites, producing the 52,55K or the IIIa mRNAs (Fig. 1a). Efficient usage of the distal IIIa 3' splice site requires late viral protein synthesis and is therefore confined to the late phase of virus infection. Here we show that, in extracts from uninfected cells, the classical SR proteins, which are essential splicing factors, inhibit IIIa pre-mRNA splicing by binding to an intronic repressor element and preventing recruitment of the U2 small nuclear ribonucleoprotein particle to the spliceosome. We further show that the viral repressor element has splicing-enhancer activity when appropriately placed in the pre-mRNA. Together, our results demonstrate that SR proteins function as activators or repressors of splicing depending on where on the pre-mRNA they bind.

  • 207.
    Kanopka, Arvydas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Mühleman, Oliver
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Petersen-Mahrt, Svend
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Estmer, Camilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Öhrmalm, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Akusjärvi, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Regulation of adenovirus alternative RNAsplicing by dephosphorylation of SR proteins1998In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 393, no 6681, 185-187 p.Article in journal (Refereed)
    Abstract [en]

    SR proteins are a family of essential splicing factors required for early recognition of splice sites during spliceosome assembly. They also function as alternative RNA splicing factors when overexpressed in vivo or added in excess to extracts in vitro. SR proteins are highly phosphorylated in vivo, a modification that is required for their function in spliceosome assembly and splicing catalysis. Here we show that SR proteins purified from late adenovirus-infected cells are inactivated as splicing enhancer or splicing repressor proteins by virus-induced dephosphorylation. We further show that the virus-encoded protein E4-ORF4 activates dephosphorylation by protein phosphatase 2A of HeLa SR proteins and converts their splicing properties into that of SR proteins purified from late adenovirus-infected cells. Taken together, our results suggest that E4-ORF4 is an important factor controlling the temporal shift in adenovirus alternative RNA splicing. We conclude that alternative pre-mRNA splicing, like many other biological processes, is regulated by reversible protein phosphorylation.

  • 208.
    Karlsson, Anders
    et al.
    Gothenburg University, Sweden.
    Karlsson, Roger
    Gothenburg University, Sweden.
    Karlsson, Mattias
    Gothenburg University, Sweden.
    Cans, Annsofie
    Gothenburg University, Sweden.
    Strömberg, Anette
    Gothenburg University, Sweden.
    Ryttsén, Frida
    Gothenburg University, Sweden.
    Orwar, Owe
    Chalmers University of Technology, Sweden.
    Molecular engineering: Networks of nanotubes and containers2001In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 409, no 6817, 150-152 p.Article in journal (Refereed)
  • 209.
    Karlsson, Jan
    et al.
    Umeå University, Faculty of Science and Technology, Ecology and Environmental Science.
    Byström, Pär
    Umeå University, Faculty of Science and Technology, Ecology and Environmental Science.
    Ask, Jenny
    Umeå University, Faculty of Science and Technology, Ecology and Environmental Science.
    Ask, Per
    Umeå University, Faculty of Science and Technology, Ecology and Environmental Science.
    Persson, Lennart
    Umeå University, Faculty of Science and Technology, Ecology and Environmental Science.
    Jansson, Mats
    Umeå University, Faculty of Science and Technology, Ecology and Environmental Science.
    Light limitation of nutrient-poor lake ecosystems2009In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 460, 506-509 p.Article in journal (Refereed)
    Abstract [en]

    Productivity denotes the rate of biomass synthesis in ecosystems and is a fundamental characteristic that frames ecosystem function and management. Limitation of productivity by nutrient availability is an established paradigm for lake ecosystems1, 2, 3. Here, we assess the relevance of this paradigm for a majority of the world's small, nutrient-poor lakes, with different concentrations of coloured organic matter4, 5. By comparing small unproductive lakes along a water colour gradient, we show that coloured terrestrial organic matter controls the key process for new biomass synthesis (the benthic primary production) through its effects on light attenuation. We also show that this translates into effects on production and biomass of higher trophic levels (benthic invertebrates and fish). These results are inconsistent with the idea that nutrient supply primarily controls lake productivity, and we propose that a large share of the world's unproductive lakes, within natural variations of organic carbon and nutrient input, are limited by light and not by nutrients. We anticipate that our result will have implications for understanding lake ecosystem function and responses to environmental change. Catchment export of coloured organic matter is sensitive to short-term natural variability and long-term, large-scale changes, driven by climate and different anthropogenic influences6, 7. Consequently, changes in terrestrial carbon cycling will have pronounced effects on most lake ecosystems by mediating changes in light climate and productivity of lakes.

  • 210. Kaukua, Nina
    et al.
    Shahidi, Maryam Khatibi
    Konstantinidou, Chrysoula
    Dyachuk, Vyacheslav
    Kaucka, Marketa
    Furlan, Alessandro
    An, Zhengwen
    Wang, Longlong
    Hultman, Isabell
    Ahrlund-Richter, Larsa
    Blom, Hans
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Brismar, Hjalmar
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Lopes, Natalia Assaife
    Pachnis, Vassilis
    Suter, Ueli
    Clevers, Hans
    Thesleff, Irma
    Sharpe, Paul
    Ernfors, Patrik
    Fried, Kaj
    Adameyko, Igor
    Glial origin of mesenchymal stem cells in a tooth model system2014In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 513, no 7519, 551-554 p.Article in journal (Refereed)
    Abstract [en]

    Mesenchymal stem cells occupy niches in stromal tissues where they provide sources of cells for specialized mesenchymal derivatives during growth and repair(1). The origins of mesenchymal stem cells have been the subject of considerable discussion, and current consensus holds that perivascular cells form mesenchymal stem cells in most tissues. The continuously growing mouse incisor tooth offers an excellent model to address the origin of mesenchymal stem cells. These stem cells dwell in a niche at the tooth apex where they produce a variety of differentiated derivatives. Cells constituting the tooth are mostly derived from two embryonic sources: neural crest ectomesenchyme and ectodermal epithelium(2). It has been thought for decades that the dental mesenchymal stem cells(3) giving rise to pulp cells and odontoblasts derive from neural crest cells after their migration in the early head and formation of ectomesenchymal tissue(4,5). Here we show that a significant population of mesenchymal stem cells during development, self-renewal and repair of a tooth are derived from peripheral nerve-associated glia. Glial cells generate multipotent mesenchymal stem cells that produce pulp cells and odontoblasts. By combining a clonal colour-coding technique(6) with tracing of peripheral glia, we provide new insights into the dynamics of tooth organogenesis and growth.

  • 211.
    Keeling, L.
    et al.
    Dept. of Anim. Environ. and Health, Swed. Univ. of Agricultural Sciences, PO Box 234, 53223 Skara, Sweden.
    Andersson, L.
    Dept. Med. Biochem. and Microbiol., Uppsala University, Box 597, 75124 Uppsala, Sweden, Dept. of Anim. Breeding and Genetics, Swed. Univ. of Agricultural Sciences, 75124 Uppsala, Sweden.
    Schutz, K.E.
    Schütz, K.E., Dept. of Anim. Environ. and Health, Swed. Univ. of Agricultural Sciences, PO Box 234, 53223 Skara, Sweden, AgResearch, Animal Behaviour and Welfare, Private Bag 3123, Hamilton, New Zealand.
    Kerje, Susanne
    Linköping University, Department of Physics, Chemistry and Biology, Zoology .
    Fredriksson, R.
    Dept. of Anim. Breeding and Genetics, Swed. Univ. of Agricultural Sciences, 75124 Uppsala, Sweden.
    Carlborg, O.
    Carlborg, Ö., Dept. of Anim. Breeding and Genetics, Swed. Univ. of Agricultural Sciences, 75124 Uppsala, Sweden, Roslin Institute, Roslin, Midlothian EH25 9PS, United Kingdom.
    Cornwallis, C.K.
    Dept. of Animal and Plant Sciences, University of Sheffield, Sheffield S10 2TN, United Kingdom.
    Pizzari, Tom
    Linköping University, Department of Physics, Chemistry and Biology, Zoology .
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Zoology .
    Feather pecking and victim pigmentation2004In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 431, no 7009, 645-646 p.Article in journal (Refereed)
    Abstract [en]

    [No abstract available]

  • 212. Keeling, Linda
    et al.
    Andersson, Leif
    Schütz, Karin E
    Kerje, Susanne
    Fredriksson, Robert
    Carlborg, Örjan
    SLU.
    Cornwallis, Charles K
    Pizzari, Tommaso
    Jensen, Per
    Chicken genomics: feather-pecking and victim pigmentation.2004In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 431, no 7009Article in journal (Refereed)
    Abstract [en]

    Feather-pecking in domestic birds is associated with cannibalism and severe welfare problems. It is a dramatic example of a spiteful behaviour in which the victim's fitness is reduced for no immediate direct benefit to the perpetrator and its evolution is unexplained. Here we show that the plumage pigmentation of a chicken may predispose it to become a victim: birds suffer more drastic feather-pecking when the colour of their plumage is due to the expression of a wild recessive allele at PMEL17, a gene that controls plumage melanization, and when these birds are relatively common in a flock. These findings, obtained using an intercross between a domestic fowl and its wild ancestor, have implications for the welfare of domestic species and offer insight into the genetic changes associated with the evolution of feather-pecking during the early stages of domestication.

  • 213.
    Kharchenko, Peter V
    et al.
    Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA.
    Alekseyenko, Artyom A
    Division of Genetics, Department of Medicine, Brigham & Women’s Hospital, Boston, Massachusetts 02115, USA.
    Schwartz, Yuri B
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Minoda, Aki
    Department of Molecular and Cell Biology, University of California at Berkeley, and Department of Genome Dynamics, Lawrence Berkeley National Lab, Berkeley, California 94720, USA.
    Riddle, Nicole C
    Department of Biology, Washington University in St Louis, St Louis, Missouri 63130, USA.
    Ernst, Jason
    MIT Computer Science and Artificial Intelligence Laboratory, Cambridge, Massachusetts 02139, USA.
    Sabo, Peter J
    Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA.
    Larschan, Erica
    Division of Genetics, Department of Medicine, Brigham & Women’s Hospital, Boston, Massachusetts 02115, USA.
    Gorchakov, Andrey A
    Division of Genetics, Department of Medicine, Brigham & Women’s Hospital, Boston, Massachusetts 02115, USA.
    Gu, Tingting
    Department of Biology, Washington University in St Louis, St Louis, Missouri 63130, USA.
    Linder-Basso, Daniela
    Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey 08854, USA.
    Plachetka, Annette
    Division of Genetics, Department of Medicine, Brigham & Women’s Hospital, Boston, Massachusetts 02115, USA.
    Shanower, Gregory
    Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey 08854, USA.
    Tolstorukov, Michael Y
    Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA.
    Luquette, Lovelace J
    Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA.
    Xi, Ruibin
    Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA.
    Jung, Youngsook L
    Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA.
    Park, Richard W
    Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA.
    Bishop, Eric P
    Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA.
    Canfield, Theresa K
    Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA.
    Sandstrom, Richard
    Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA.
    Thurman, Robert E
    Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA.
    MacAlpine, David M
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
    Stamatoyannopoulos, John A
    Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA.
    Kellis, Manolis
    MIT Computer Science and Artificial Intelligence Laboratory, Cambridge, Massachusetts 02139, USA.
    Elgin, Sarah C R
    Department of Biology, Washington University in St Louis, St Louis, Missouri 63130, USA.
    Kuroda, Mitzi I
    Division of Genetics, Department of Medicine, Brigham & Women’s Hospital, Boston, Massachusetts 02115, USA.
    Pirrotta, Vincenzo
    Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey 08854, USA.
    Karpen, Gary H
    Department of Molecular and Cell Biology, University of California at Berkeley, and Department of Genome Dynamics, Lawrence Berkeley National Lab, Berkeley, California 94720, USA.
    Park, Peter J
    Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA.
    Comprehensive analysis of the chromatin landscape in Drosophila melanogaster2011In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Nature, ISSN 1476-4687 EISSN, Vol. 471, no 7339, 480-485 p.Article in journal (Refereed)
    Abstract [en]

    Chromatin is composed of DNA and a variety of modified histones and non-histone proteins, which have an impact on cell differentiation, gene regulation and other key cellular processes. Here we present a genome-wide chromatin landscape for Drosophila melanogaster based on eighteen histone modifications, summarized by nine prevalent combinatorial patterns. Integrative analysis with other data (non-histone chromatin proteins, DNase I hypersensitivity, GRO-Seq reads produced by engaged polymerase, short/long RNA products) reveals discrete characteristics of chromosomes, genes, regulatory elements and other functional domains. We find that active genes display distinct chromatin signatures that are correlated with disparate gene lengths, exon patterns, regulatory functions and genomic contexts. We also demonstrate a diversity of signatures among Polycomb targets that include a subset with paused polymerase. This systematic profiling and integrative analysis of chromatin signatures provides insights into how genomic elements are regulated, and will serve as a resource for future experimental investigations of genome structure and function.

  • 214. Khmelinskii, Anton
    et al.
    Blaszczak, Ewa
    Pantazopoulou, Marina
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Fischer, Bernd
    Omnus, Deike J.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Le Dez, Gaelle
    Brossard, Audrey
    Gunnarsson, Alexander
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Barry, Joseph D.
    Meurer, Matthias
    Kirrmaier, Daniel
    Boone, Charles
    Huber, Wolfgang
    Rabut, Gwenael
    Ljungdahl, Per O.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Knop, Michael
    Protein quality control at the inner nuclear membrane2014In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 516, no 7531, 410-+ p.Article in journal (Refereed)
    Abstract [en]

    The nuclear envelope is a double membrane that separates the nucleus from the cytoplasm. The inner nuclear membrane (INM) functions in essential nuclear processes including chromatin organization and regulation of gene expression(1). The outer nuclear membrane is continuous with the endoplasmic reticulum and is the site of membrane protein synthesis. Protein homeostasis in this compartment is ensured by endoplasmic-reticulum-associated protein degradation (ERAD) pathways that in yeast involve the integral membrane E3 ubiquitin ligases Hrd1 and Doa10 operating with the E2 ubiquitin-conjugating enzymes Ubc6 and Ubc7 (refs 2, 3). However, little is known about protein quality control at the INM. Here we describe a protein degradation pathway at the INM in yeast (Saccharomyces cerevisiae) mediated by the Asicomplex consisting of the RING domain proteins Asi1 and Asi3 (ref. 4). We report that the Asi complex functions together with the ubiquitin-conjugating enzymes Ubc6 and Ubc7 to degrade soluble and integral membrane proteins. Genetic evidence suggests that the Asi ubiquitin ligase defines a pathway distinct from, but complementary to, ERAD. Using unbiased screening with a novel genome-wide yeast library based on a tandem fluorescent protein timer(5), we identify more than 50 substrates of the Asi, Hrd1 and Doa10 E3 ubiquitin ligases. We show that the Asi ubiquitin ligase is involved in degradation of mislocalized integral membrane proteins, thus acting to maintain and safeguard the identity of the INM.

  • 215.
    Kinoshita, Masaharu
    et al.
    National Institute for Physiological Sciences, Myodaiji, Okazaki .
    Matsui, Ryosuke
    Kyoto University.
    Kato, Shigeki
    Fukushima Medical University School of Medicine, Fukushima.
    Hasegawa, Taku
    Kyoto University.
    Kasahara, Hironori
    Kyoto University.
    Isa, Kaoru
    National Institute for Physiological Sciences, Myodaiji, Okazaki .
    Watakabe, Akiya
    National Institute for Basic Biology, Okazaki, he Graduate University for Advanced Studies (Sokendai), Hayama, Kanagawa.
    Yamamori, Tetsuo
    National Institute for Basic Biology, Okazaki, he Graduate University for Advanced Studies (Sokendai), Hayama, Kanagawa.
    Nishimura, Yukio
    National Institute for Physiological Sciences, Myodaiji, Okazaki .
    Alstermark, Bror
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Watanabe, Dai
    Kyoto University.
    Kobayashi, Kazuto
    Fukushima Medical University School of Medicine, Fukushima.
    Isa, Tadashi
    National Institute for Physiological Sciences, Myodaiji, Okazaki , he Graduate University for Advanced Studies (Sokendai), Hayama, Kanagawa.
    Genetic dissection of the circuit for hand dexterity in primates2012In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 487, no 7406, 235-U1510 p.Article in journal (Refereed)
    Abstract [en]

    It is generally accepted that the direct connection from the motor cortex to spinal motor neurons is responsible for dexterous hand movements in primates(1-3). However, the role of the 'phylogenetically older' indirect pathways from the motor cortex to motor neurons, mediated by spinal interneurons, remains elusive. Here we used a novel double-infection technique to interrupt the transmission through the propriospinal neurons (PNs)(4-6), which act as a relay of the indirect pathway in macaque monkeys (Macaca fuscata and Macaca mulatta). The PNs were double infected by injection of a highly efficient retrograde gene-transfer vector into their target area and subsequent injection of adeno-associated viral vector at the location of cell somata. This method enabled reversible expression of green fluorescent protein (GFP)-tagged tetanus neurotoxin, thereby permitting the selective and temporal blockade of the motor cortex-PN-motor neuron pathway. This treatment impaired reach and grasp movements, revealing a critical role for the PN-mediated pathway in the control of hand dexterity. Anti-GFP immunohistochemistry visualized the cell bodies and axonal trajectories of the blocked PNs, which confirmed their anatomical connection to motor neurons. This pathway-selective and reversible technique for blocking neural transmission does not depend on cell-specific promoters or transgenic techniques, and is a new and powerful tool for functional dissection in system-level neuroscience studies.

  • 216. Kirkby, Jasper
    et al.
    Duplissy, Jonathan
    Sengupta, Kamalika
    Frege, Carla
    Gordon, Hamish
    Williamson, Christina
    Heinritzi, Martin
    Simon, Mario
    Yan, Chao
    Almeida, João
    Tröstl, Jasmin
    Nieminen, Tuomo
    Ortega, Ismael K.
    Wagner, Robert
    Adamov, Alexey
    Amorim, Antonio
    Bernhammer, Anne-Kathrin
    Bianchi, Federico
    Breitenlechner, Martin
    Brilke, Sophia
    Chen, Xuemeng
    Craven, Jill
    Dias, Antonio
    Ehrhart, Sebastian
    Flagan, Richard C.
    Franchin, Alessandro
    Fuchs, Claudia
    Guida, Roberto
    Hakala, Jani
    Hoyle, Christopher R.
    Jokinen, Tuija
    Junninen, Heikki
    Kangasluoma, Juha
    Kim, Jaeseok
    Krapf, Manuel
    Kürten, Andreas
    Laaksonen, Ari
    Lehtipalo, Katrianne
    Makhmutov, Vladimir
    Mathot, Serge
    Molteni, Ugo
    Onnela, Antti
    Peräkylä, Otso
    Piel, Felix
    Petäjä, Tuukka
    Praplan, Arnaud P.
    Pringle, Kirsty
    Rap, Alexandru
    Richards, Nigel A. D.
    Riipinen, Ilona
    Stockholm University, Faculty of Science, Department of Applied Environmental Science (ITM).
    Rissanen, Matti P.
    Rondo, Linda
    Sarnela, Nina
    Schobesberger, Siegfried
    Scott, Catherine E.
    Seinfeld, John H.
    Sipilä, Mikko
    Steiner, Gerhard
    Stozhkov, Yuri
    Stratmann, Frank
    Tomé, Antonio
    Virtanen, Annele
    Vogel, Alexander L.
    Wagner, Andrea C.
    Wagner, Paul E.
    Weingartner, Ernest
    Wimmer, Daniela
    Winkler, Paul M.
    Ye, Penglin
    Zhang, Xuan
    Hansel, Armin
    Dommen, Josef
    Donahue, Neil M.
    Worsnop, Douglas R.
    Baltensperger, Urs
    Kulmala, Markku
    Carslaw, Kenneth S.
    Curtius, Joachim
    Ion-induced nucleation of pure biogenic particles2016In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 533, no 7604, 521-526 p.Article in journal (Refereed)
    Abstract [en]

    Atmospheric aerosols and their effect on clouds are thought to be important for anthropogenic radiative forcing of the climate, yet remain poorly understood(1). Globally, around half of cloud condensation nuclei originate from nucleation of atmospheric vapours(2). It is thought that sulfuric acid is essential to initiate most particle formation in the atmosphere(3,4), and that ions have a relatively minor role(5). Some laboratory studies, however, have reported organic particle formation without the intentional addition of sulfuric acid, although contamination could not be excluded(6,7). Here we present evidence for the formation of aerosol particles from highly oxidized biogenic vapours in the absence of sulfuric acid in a large chamber under atmospheric conditions. The highly oxygenated molecules (HOMs) are produced by ozonolysis of a-pinene. We find that ions from Galactic cosmic rays increase the nucleation rate by one to two orders of magnitude compared with neutral nucleation. Our experimental findings are supported by quantum chemical calculations of the cluster binding energies of representative HOMs. Ion-induced nucleation of pure organic particles constitutes a potentially widespread source of aerosol particles in terrestrial environments with low sulfuric acid pollution.

  • 217.
    Korn, Andreas
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Astronomy and Space Physics.
    Grundahl, Frank
    Richard, O.
    Barklem, Paul
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Astronomy and Space Physics.
    Mashonkina, Ludmila
    Collet, Remo
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Astronomy and Space Physics.
    Piskunov, Nikolai
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Astronomy and Space Physics.
    Gustafsson, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Astronomy and Space Physics.
    A probable stellar solution to the cosmological lithium discrepancy2006In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 442, no 7103, 657-659 p.Article in journal (Refereed)
    Abstract [en]

    The measurement of the cosmic microwave background has strongly constrained the cosmological parameters of the Universe. When the measured density of baryons (ordinary matter) is combined with standard Big Bang nucleosynthesis calculations, the amounts of hydrogen, helium and lithium produced shortly after the Big Bang can be predicted with unprecedented precision. The predicted primordial lithium abundance is a factor of two to three higher than the value measured in the atmospheres of old stars. With estimated errors of 10 to 25%, this cosmological lithium discrepancy seriously challenges our understanding of stellar physics, Big Bang nucleosynthesis or both. Certain modifications to nucleosynthesis have been proposed, but found experimentally not to be viable. Diffusion theory, however, predicts atmospheric abundances of stars to vary with time, which offers a possible explanation of the discrepancy. Here we report spectroscopic observations of stars in the metal-poor globular cluster NGC6397 that reveal trends of atmospheric abundance with evolutionary stage for various elements. These element-specific trends are reproduced by stellar-evolution models with diffusion and turbulent mixing. We thus conclude that diffusion is predominantly responsible for the low apparent stellar lithium abundance in the atmospheres of old stars by transporting the lithium deep into the star.

  • 218. Kupitz, Christopher
    et al.
    Basu, Shibom
    Grotjohann, Ingo
    Fromme, Raimund
    Zatsepin, Nadia A
    Rendek, Kimberly N
    Hunter, Mark S
    Shoeman, Robert L
    White, Thomas A
    Wang, Dingjie
    James, Daniel
    Yang, Jay-How
    Cobb, Danielle E
    Reeder, Brenda
    Sierra, Raymond G
    Liu, Haiguang
    Barty, Anton
    Aquila, Andrew L
    Deponte, Daniel
    Kirian, Richard A
    Bari, Sadia
    Bergkamp, Jesse J
    Beyerlein, Kenneth R
    Bogan, Michael J
    Caleman, Carl
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Molecular and Condensed Matter Physics.
    Chao, Tzu-Chiao
    Conrad, Chelsie E
    Davis, Katherine M
    Fleckenstein, Holger
    Galli, Lorenzo
    Hau-Riege, Stefan P
    Kassemeyer, Stephan
    Laksmono, Hartawan
    Liang, Mengning
    Lomb, Lukas
    Marchesini, Stefano
    Martin, Andrew V
    Messerschmidt, Marc
    Milathianaki, Despina
    Nass, Karol
    Ros, Alexandra
    Roy-Chowdhury, Shatabdi
    Schmidt, Kevin
    Seibert, Marvin
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular biophysics.
    Steinbrener, Jan
    Stellato, Francesco
    Yan, Lifen
    Yoon, Chunhong
    Moore, Thomas A
    Moore, Ana L
    Pushkar, Yulia
    Williams, Garth J
    Boutet, Sébastien
    Doak, R Bruce
    Weierstall, Uwe
    Frank, Matthias
    Chapman, Henry N
    Spence, John C H
    Fromme, Petra
    Serial time-resolved crystallography of photosystem II using a femtosecond X-ray laser2014In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 513, no 7517, 261-265 p.Article in journal (Refereed)
    Abstract [en]

    Photosynthesis, a process catalysed by plants, algae and cyanobacteria converts sunlight to energy thus sustaining all higher life on Earth. Two large membrane protein complexes, photosystem I and II (PSI and PSII), act in series to catalyse the light-driven reactions in photosynthesis. PSII catalyses the light-driven water splitting process, which maintains the Earth's oxygenic atmosphere. In this process, the oxygen-evolving complex (OEC) of PSII cycles through five states, S0 to S4, in which four electrons are sequentially extracted from the OEC in four light-driven charge-separation events. Here we describe time resolved experiments on PSII nano/microcrystals from Thermosynechococcus elongatus performed with the recently developed technique of serial femtosecond crystallography. Structures have been determined from PSII in the dark S1 state and after double laser excitation (putative S3 state) at 5 and 5.5 Å resolution, respectively. The results provide evidence that PSII undergoes significant conformational changes at the electron acceptor side and at the Mn4CaO5 core of the OEC. These include an elongation of the metal cluster, accompanied by changes in the protein environment, which could allow for binding of the second substrate water molecule between the more distant protruding Mn (referred to as the 'dangler' Mn) and the Mn3CaOx cubane in the S2 to S3 transition, as predicted by spectroscopic and computational studies. This work shows the great potential for time-resolved serial femtosecond crystallography for investigation of catalytic processes in biomolecules.

  • 219.
    Kurokawa, R.
    et al.
    University of California, San Diego, USA.
    Söderström, Mats
    University of California, San Diego, USA.
    Hörlein, A.
    University of California, San Diego, USA.
    Halachmi, S.
    Dana Farber Cancer Institute, Boston, Massachusetts, USA .
    Brown, M.
    Dana Farber Cancer Institute, Boston, Massachusetts, USA .
    Rosenfeld, M. G.
    University of California, San Diego, USA.
    Glass, C. K.
    University of California, San Diego, USA.
    Polarity-specific activities of retinoic acid receptors determined by a co-repressor.1995In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 377, no 6548, 451-454 p.Article in journal (Refereed)
    Abstract [en]

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

  • 220.
    Kusumbe, Anjali P.
    et al.
    Max Planck Inst Mol Biomed, Dept Tissue Morphogenesis, D-48149 Munster, Germany.;Univ Munster, Fac Med, D-48149 Munster, Germany..
    Ramasamy, Saravana K.
    Max Planck Inst Mol Biomed, Dept Tissue Morphogenesis, D-48149 Munster, Germany.;Univ Munster, Fac Med, D-48149 Munster, Germany..
    Itkin, Tomer
    Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel..
    Mae, Maarja Andaloussi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Langen, Urs H.
    Max Planck Inst Mol Biomed, Dept Tissue Morphogenesis, D-48149 Munster, Germany.;Univ Munster, Fac Med, D-48149 Munster, Germany..
    Betsholtz, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    Lapidot, Tsvee
    Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel..
    Adams, Ralf H.
    Max Planck Inst Mol Biomed, Dept Tissue Morphogenesis, D-48149 Munster, Germany.;Univ Munster, Fac Med, D-48149 Munster, Germany..
    Age-dependent modulation of vascular niches for haematopoietic stem cells2016In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 532, no 7599, 380-+ p.Article in journal (Refereed)
    Abstract [en]

    Blood vessels define local microenvironments in the skeletal system, play crucial roles in osteogenesis and provide niches for haematopoietic stem cells(1-6). The properties of nicheforming vessels and their changes in the ageing organism remain incompletely understood. Here we show that Notch signalling in endothelial cells leads to the expansion of haematopoietic stem cell niches in bone, which involves increases in CD31-positive capillaries and platelet-derived growth factor receptor-beta (PDGFR beta)-positive perivascular cells, arteriole formation and elevated levels of cellular stem cell factor. Although endothelial hypoxia-inducible factor signalling promotes some of these changes, it fails to enhance vascular niche function because of a lack of arterialization and expansion of PDGFR beta-positive cells. In ageing mice, niche-forming vessels in the skeletal system are strongly reduced but can be restored by activation of endothelial Notch signalling. These findings indicate that vascular niches for haematopoietic stem cells are part of complex, age-dependent microenvironments involving multiple cell populations and vessel subtypes.

  • 221. Lamichhaney, Sangeet
    et al.
    Berglund, Jonas
    Almen, Markus Sallman
    Maqbool, Khurram
    Grabherr, Manfred
    Martinez-Barrio, Alvaro
    Promerova, Marta
    Rubin, Carl-Johan
    Wang, Chao
    Zamani, Neda
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Grant, B. Rosemary
    Grant, Peter R.
    Webster, Matthew T.
    Andersson, Leif
    Evolution of Darwin's finches and their beaks revealed by genome sequencing2015In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 518, no 7539Article in journal (Refereed)
    Abstract [en]

    Darwin's finches, inhabiting the Galapagos archipelago and Cocos Island, constitute an iconic model for studies of speciation and adaptive evolution. Here we report the results of whole-genome re-sequencing of 120 individuals representing all of the Darwin's finch species and two close relatives' Phylogenetic analysis reveals important discrepancies with the phenotype-based taxonomy. We find extensive evidence for interspecific gene flow throughout the radiation. Hybridization has given rise to species of mixed ancestry. A 240 kilobase haplotype encompassing the ALX1 gene that encodes a transcription factor affecting craniofacial. development is strongly associated with beak shape diversity across Darwin's finch species as well as within the medium ground finch (Geospiza fortis) a species that has undergone rapid evolution of beak shape in response to environmental changes. The ALX1 haplotype has contributed to diversification of beak shapes among the Darwin's finches and thereby, to an expanded utilization of food resources.

  • 222.
    Lamichhaney, Sangeet
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Berglund, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Almen, Markus Sällman
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Maqbool, Khurram
    Grabherr, Manfred
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Martinez-Barrio, Alvaro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Promerova, Marta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Rubin, Carl-Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Wang, Chao
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Zamani, Neda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Grant, B. Rosemary
    Grant, Peter R.
    Webster, Matthew T.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Evolution of Darwin's finches and their beaks revealed by genome sequencing2015In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 518, no 7539Article in journal (Refereed)
    Abstract [en]

    Darwin's finches, inhabiting the Galapagos archipelago and Cocos Island, constitute an iconic model for studies of speciation and adaptive evolution. Here we report the results of whole-genome re-sequencing of 120 individuals representing all of the Darwin's finch species and two close relatives' Phylogenetic analysis reveals important discrepancies with the phenotype-based taxonomy. We find extensive evidence for interspecific gene flow throughout the radiation. Hybridization has given rise to species of mixed ancestry. A 240 kilobase haplotype encompassing the ALX1 gene that encodes a transcription factor affecting craniofacial. development is strongly associated with beak shape diversity across Darwin's finch species as well as within the medium ground finch (Geospiza fortis) a species that has undergone rapid evolution of beak shape in response to environmental changes. The ALX1 haplotype has contributed to diversification of beak shapes among the Darwin's finches and thereby, to an expanded utilization of food resources.

  • 223.
    Langner, Joakim
    et al.
    SMHI, Research Department, Air quality.
    RODHE, H
    CRUTZEN, PJ
    ZIMMERMANN, P
    ANTHROPOGENIC INFLUENCE ON THE DISTRIBUTION OF TROPOSPHERIC SULFATE AEROSOL1992In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 359, no 6397, 712-716 p.Article in journal (Refereed)
    Abstract [en]

    HUMAN activities have increased global emissions of sulphur gases by about a factor of three during the past century, leading to increased sulphate aerosol concentrations, mainly in the Northern Hemisphere. Sulphate aerosols can affect the climate directly, by increasing the backscattering of solar radiation in cloud-free air, and indirectly, by providing additional cloud condensation nuclei1-4. Here we use a global transport-chemistry model to estimate the changes in the distribution of tropospheric sulphate aerosol and deposition of non-seasalt sulphur that have occurred since pre-industrial times. The increase in sulphate aerosol concentration is small over the Southern Hemisphere oceans, but reaches a factor of 100 over northern Europe in winter. Our calculations indicate, however, that at most 6% of the anthropogenic sulphur emissions is available for the formation of new aerosol particles. This is because about one-half of the sulphur dioxide is deposited on the Earth's surface, and most of the remainder is oxidized in cloud droplets so that the sulphate becomes associated with pre-existing particles. Even so, the rate of formation of new sulphate particles may have doubled since pre-industrial times.

  • 224. Lappalainen, Tuuli
    et al.
    Sammeth, Michael
    Friedländer, Marc R
    't Hoen, Peter A C
    Monlong, Jean
    Rivas, Manuel A
    Gonzàlez-Porta, Mar
    Kurbatova, Natalja
    Griebel, Thasso
    Ferreira, Pedro G
    Barann, Matthias
    Wieland, Thomas
    Greger, Liliana
    van Iterson, Maarten
    Almlöf, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ribeca, Paolo
    Pulyakhina, Irina
    Esser, Daniela
    Giger, Thomas
    Tikhonov, Andrew
    Sultan, Marc
    Bertier, Gabrielle
    Macarthur, Daniel G
    Lek, Monkol
    Lizano, Esther
    Buermans, Henk P J
    Padioleau, Ismael
    Schwarzmayr, Thomas
    Karlberg, Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ongen, Halit
    Kilpinen, Helena
    Beltran, Sergi
    Gut, Marta
    Kahlem, Katja
    Amstislavskiy, Vyacheslav
    Stegle, Oliver
    Pirinen, Matti
    Montgomery, Stephen B
    Donnelly, Peter
    McCarthy, Mark I
    Flicek, Paul
    Strom, Tim M
    Lehrach, Hans
    Schreiber, Stefan
    Sudbrak, Ralf
    Carracedo, Angel
    Antonarakis, Stylianos E
    Häsler, Robert
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    van Ommen, Gert-Jan
    Brazma, Alvis
    Meitinger, Thomas
    Rosenstiel, Philip
    Guigó, Roderic
    Gut, Ivo G
    Estivill, Xavier
    Dermitzakis, Emmanouil T
    Transcriptome and genome sequencing uncovers functional variation in humans2013In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 501, no 7468, 506-511 p.Article in journal (Refereed)
    Abstract [en]

    Genome sequencing projects are discovering millions of genetic variants in humans, and interpretation of their functional effects is essential for understanding the genetic basis of variation in human traits. Here we report sequencing and deep analysis of messenger RNA and microRNA from lymphoblastoid cell lines of 462 individuals from the 1000 Genomes Project-the first uniformly processed high-throughput RNA-sequencing data from multiple human populations with high-quality genome sequences. We discover extremely widespread genetic variation affecting the regulation of most genes, with transcript structure and expression level variation being equally common but genetically largely independent. Our characterization of causal regulatory variation sheds light on the cellular mechanisms of regulatory and loss-of-function variation, and allows us to infer putative causal variants for dozens of disease-associated loci. Altogether, this study provides a deep understanding of the cellular mechanisms of transcriptome variation and of the landscape of functional variants in the human genome.

  • 225.
    Larsbrink, Johan
    et al.
    KTH, School of Biotechnology (BIO), Glycoscience.
    Rogers, Theresa E.
    Hemsworth, Glyn R.
    McKee, Lauren S.
    KTH, School of Biotechnology (BIO), Glycoscience. KTH, School of Chemical Science and Engineering (CHE), Centres, Wallenberg Wood Science Center.
    Tauzin, Alexandra S.
    Spadiut, Oliver
    KTH, School of Biotechnology (BIO), Glycoscience. KTH, School of Chemical Science and Engineering (CHE), Centres, Wallenberg Wood Science Center.
    Klinter, Stefan
    KTH, School of Biotechnology (BIO), Glycoscience.
    Pudlo, Nicholas A.
    Urs, Karthik
    Koropatkin, Nicole M.
    Creagh, A. Louise
    Haynes, Charles A.
    Kelly, Amelia G.
    Nilsson Cederholm, Stefan
    KTH, School of Biotechnology (BIO), Glycoscience.
    Davies, Gideon J.
    Martens, Eric C.
    Brumer, Harry
    KTH, School of Biotechnology (BIO), Glycoscience.
    A discrete genetic locus confers xyloglucan metabolism in select human gut Bacteroidetes2014In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 506, no 7489, 498-502 p.Article in journal (Refereed)
    Abstract [en]

    A well-balanced human diet includes a significant intake of non-starch polysaccharides, collectively termed 'dietary fibre', from the cell walls of diverse fruits and vegetables(1). Owing to the paucity of alimentary enzymes encoded by the human genome(2), our ability to derive energy from dietary fibre depends on the saccharification and fermentation of complex carbohydrates by the massive microbial community residing in our distal gut(3,4). The xyloglucans (XyGs) are a ubiquitous family of highly branched plant cell wall polysaccharides(5,6) whose mechanism(s) of degradation in the human gut and consequent importance in nutrition have been unclear(1,7,8). Here we demonstrate that a single, complex gene locus in Bacteroides ovatus confers XyG catabolism in this common colonic symbiont. Through targeted gene disruption, biochemical analysis of all predicted glycoside hydrolases and carbohydrate-binding proteins, and three-dimensional structural determination of the vanguard endo-xyloglucanase, we reveal the molecular mechanisms through which XyGs are hydrolysed to component monosaccharides for further metabolism. We also observe that orthologous XyG utilization loci (XyGULs) serve as genetic markers of XyG catabolism in Bacteroidetes, that XyGULs are restricted to a limited number of phylogenetically diverse strains, and that XyGULs are ubiquitous in surveyed human metagenomes. Our findings reveal that the metabolism of even highly abundant components of dietary fibre may be mediated by niche species, which has immediate fundamental and practical implications for gut symbiont population ecology in the context of human diet, nutrition and health(9-12).

  • 226.
    Larsson, Josefin
    et al.
    Stockholm University, Faculty of Science, Department of Astronomy. Stockholm University, Faculty of Science, The Oskar Klein Centre for Cosmo Particle Physics (OKC).
    Fransson, Claes
    Stockholm University, Faculty of Science, Department of Astronomy. Stockholm University, Faculty of Science, The Oskar Klein Centre for Cosmo Particle Physics (OKC).
    Östlin, Göran
    Stockholm University, Faculty of Science, Department of Astronomy. Stockholm University, Faculty of Science, The Oskar Klein Centre for Cosmo Particle Physics (OKC).
    Gröningsson, P.
    Stockholm University, Faculty of Science, Department of Astronomy. Stockholm University, Faculty of Science, The Oskar Klein Centre for Cosmo Particle Physics (OKC).
    Jerkstrand, Anders
    Stockholm University, Faculty of Science, Department of Astronomy. Stockholm University, Faculty of Science, The Oskar Klein Centre for Cosmo Particle Physics (OKC).
    Kozma, Cecilia
    Stockholm University, Faculty of Science, Department of Astronomy. Stockholm University, Faculty of Science, The Oskar Klein Centre for Cosmo Particle Physics (OKC).
    Sollerman, Jesper
    Stockholm University, Faculty of Science, Department of Astronomy. Stockholm University, Faculty of Science, The Oskar Klein Centre for Cosmo Particle Physics (OKC).
    Challis, P.
    Kirshner, R. P.
    Chevalier, R. A.
    Heng, K.
    McCray, R.
    Suntzeff, N. B.
    Bouchet, P.
    Crotts, A.
    Danziger, J.
    Dwek, E.
    France, K.
    Garnavich, P. M.
    Lawrence, S. S.
    Leibundgut, B.
    Lundqvist, Peter
    Stockholm University, Faculty of Science, Department of Astronomy. Stockholm University, Faculty of Science, The Oskar Klein Centre for Cosmo Particle Physics (OKC).
    Panagia, N.
    Pun, C. S. J.
    Smith, N.
    Sonneborn, G.
    Wang, L.
    Wheeler, J. C.
    X-ray illumination of the ejecta of supernova 1987A2011In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 474, no 7352, 484-486 p.Article in journal (Refereed)
    Abstract [en]

    When a massive star explodes as a supernova, substantial amounts of radioactive elements-primarily (56)Ni, (57)Ni and (44)Ti-are produced(1). After the initial flash of light from shock heating, the fading light emitted by the supernova is due to the decay of these elements(2). However, after decades, the energy powering a supernova remnant comes from the shock interaction between the ejecta and the surrounding medium(3). The transition to this phase has hitherto not been observed: supernovae occur too infrequently in the Milky Way to provide a young example, and extragalactic supernovae are generally too faint and too small. Here we report observations that show this transition in the supernova SN 1987A in the Large Magellanic Cloud. From 1994 to 2001, the ejecta faded owing to radioactive decay of (44)Ti as predicted. Then the flux started to increase, more than doubling by the end of 2009. We show that this increase is the result of heat deposited by X-rays produced as the ejecta interacts with the surrounding material. In time, the X-rays will penetrate farther into the ejecta, enabling us to analyse the structure and chemistry of the vanished star.

  • 227.
    Lassance, J-M
    et al.
    Department of Biology, Lund University, 22362 Lund, Sweden.
    Groot, A T
    Department of Entomology, Max-Planck Institute for Chemical Ecology, 07745 Jena, Germany.
    Liénard, M A
    Department of Biology, Lund University, 22362 Lund, Sweden.
    Antony, B
    Department of Biology, Lund University, 22362 Lund, Sweden.
    Borgwardt, C
    Department of Entomology, Max-Planck Institute for Chemical Ecology, 07745 Jena, Germany.
    Andersson, Fredrik
    Mid Sweden University, Faculty of Science, Technology and Media, Department of Natural Sciences, Engineering and Mathematics.
    Hedenström, Erik
    Mid Sweden University, Faculty of Science, Technology and Media, Department of Natural Sciences, Engineering and Mathematics.
    Heckel, D G
    Department of Entomology, Max-Planck Institute for Chemical Ecology, 07745 Jena, Germany.
    Löfstedt, C
    Department of Biology, Lund University, 22362 Lund, Sweden.
    Allelic variation in a fatty-acyl reductase gene causes divergence in moth sex pheromones2010In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 466, no 7305, 486-489 p.Article in journal (Refereed)
    Abstract [en]

    Pheromone-based behaviours are crucial in animals from insects to mammals, and reproductive isolation is often based on pheromone differences. However, the genetic mechanisms by which pheromone signals change during the evolution of new species are largely unknown. In the sexual communication system of moths (Insecta: Lepidoptera), females emit a species-specific pheromone blend that attracts males over long distances. The European corn borer, Ostrinia nubilalis, consists of two sex pheromone races, Z and E, that use different ratios of the cis and trans isomers of acetate pheromone components. This subtle difference leads to strong reproductive isolation in the field between the two races, which could represent a first step in speciation. Female sex pheromone production and male behavioural response are under the control of different major genes, but the identity of these genes is unknown. Here we show that allelic variation in a fatty-acyl reductase gene essential for pheromone biosynthesis accounts for the phenotypic variation in female pheromone production, leading to race-specific signals. Both the cis and trans isomers of the pheromone precursors are produced by both races, but the precursors are differentially reduced to yield opposite ratios in the final pheromone blend as a result of the substrate specificity of the enzymes encoded by the Z and E alleles. This is the first functional characterization of a gene contributing to intraspecific behavioural reproductive isolation in moths, highlighting the importance of evolutionary diversification in a lepidopteran-specific family of reductases. Accumulation of substitutions in the coding region of a single biosynthetic enzyme can produce pheromone differences resulting in reproductive isolation, with speciation as a potential end result.

     

     

  • 228.
    Laurell, Fredrik
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Laser Physics.
    Margulis, W.
    Lesche, B.
    Imagingthe χ2 grating in a frequency doubling fibre1995In: Nature, ISSN 0028-0836, E-ISSN 1476-4687Article in journal (Refereed)
  • 229. Lavik, Gaute
    et al.
    Stührmann, Torben
    Brüchert, Volker
    Stockholm University, Faculty of Science, Department of Geology and Geochemistry. Geokemi. Stockholm University.
    van der Plas, Anja
    Ministry of Fisheries and Marine Resources.
    Mohrholz, Volker
    Baltic Sea Research Institute.
    Mussmann, Marc
    Max-Planck Institute for marine Microbiology.
    Lam, Phyllis
    Max-Planck Institute for marine Microbiology.
    Fuchs, Bernhard
    Max-Planck Institute for marine Microbiology.
    Amann, Rudolf
    Max-Planck Institute for marine Microbiology.
    Lass, Uli
    Baltic Sea Research Institute.
    Kuypers, Marcel
    Max-Planck Institute for Marine Microbiology.
    Detoxification of sulphidic African shelf waters by blooming chemolithotrophs2009In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 457, no 7229, 581-584 p.Article in journal (Refereed)
  • 230. Lazaridis, Iosif
    et al.
    Patterson, Nick
    Mittnik, Alissa
    Renaud, Gabriel
    Mallick, Swapan
    Kirsanow, Karola
    Sudmant, Peter H.
    Schraiber, Joshua G.
    Castellano, Sergi
    Lipson, Mark
    Berger, Bonnie
    Economou, Christos
    Stockholm University, Faculty of Humanities, Department of Archaeology and Classical Studies, Archaeological Research Laboratory.
    Bollongino, Ruth
    Fu, Qiaomei
    Bos, Kirsten I.
    Nordenfelt, Susanne
    Li, Heng
    de Filippo, Cesare
    Pruefer, Kay
    Sawyer, Susanna
    Posth, Cosimo
    Haak, Wolfgang
    Hallgren, Fredrik
    Fornander, Elin
    Rohland, Nadin
    Delsate, Dominique
    Francken, Michael
    Guinet, Jean-Michel
    Wahl, Joachim
    Ayodo, George
    Babiker, Hamza A.
    Bailliet, Graciela
    Balanovska, Elena
    Balanovsky, Oleg
    Barrantes, Ramiro
    Bedoya, Gabriel
    Ben-Ami, Haim
    Bene, Judit
    Berrada, Fouad
    Bravi, Claudio M.
    Brisighelli, Francesca
    Busby, George B. J.
    Cali, Francesco
    Churnosov, Mikhail
    Cole, David E. C.
    Corach, Daniel
    Damba, Larissa
    van Driem, George
    Dryomov, Stanislav
    Dugoujon, Jean-Michel
    Fedorova, Sardana A.
    Romero, Irene Gallego
    Gubina, Marina
    Hammer, Michael
    Henn, Brenna M.
    Hervig, Tor
    Hodoglugil, Ugur
    Jha, Aashish R.
    Karachanak-Yankova, Sena
    Khusainova, Rita
    Khusnutdinova, Elza
    Kittles, Rick
    Kivisild, Toomas
    Klitz, William
    Kucinskas, Vaidutis
    Kushniarevich, Alena
    Laredj, Leila
    Litvinov, Sergey
    Loukidis, Theologos
    Mahley, Robert W.
    Melegh, Bela
    Metspalu, Ene
    Molina, Julio
    Mountain, Joanna
    Nakkalajarvi, Klemetti
    Nesheva, Desislava
    Nyambo, Thomas
    Osipova, Ludmila
    Parik, Jueri
    Platonov, Fedor
    Posukh, Olga
    Romano, Valentino
    Rothhammer, Francisco
    Rudan, Igor
    Ruizbakiev, Ruslan
    Sahakyan, Hovhannes
    Sajantila, Antti
    Salas, Antonio
    Starikovskaya, Elena B.
    Tarekegn, Ayele
    Toncheva, Draga
    Turdikulova, Shahlo
    Uktveryte, Ingrida
    Utevska, Olga
    Vasquez, Rene
    Villena, Mercedes
    Voevoda, Mikhail
    Winkler, Cheryl A.
    Yepiskoposyan, Levon
    Zalloua, Pierre
    Zemunik, Tatijana
    Cooper, Alan
    Capelli, Cristian
    Thomas, Mark G.
    Ruiz-Linares, Andres
    Tishkoff, Sarah A.
    Singh, Lalji
    Thangaraj, Kumarasamy
    Villems, Richard
    Comas, David
    Sukernik, Rem
    Metspalu, Mait
    Meyer, Matthias
    Eichler, Evan E.
    Burger, Joachim
    Slatkin, Montgomery
    Paeaebo, Svante
    Kelso, Janet
    Reich, David
    Krause, Johannes
    Ancient human genomes suggest three ancestral populations for present-day Europeans2014In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 513, no 7518, 409-+ p.Article in journal (Refereed)
    Abstract [en]

    We sequenced the genomes of a similar to 7,000-year-old farmer from Germany and eight similar to 8,000-year-old hunter-gatherers from Luxembourg and Sweden. We analysed these and other ancient genomes(1-4) with 2,345 contemporary humans to show that most present-day Europeans derive from at least three highly differentiated populations: west European hunter-gatherers, who contributed ancestry to all Europeans but not to Near Easterners; ancient north Eurasians related to Upper Palaeolithic Siberians(3), who contributed to both Europeans and Near Easterners; and early European farmers, who were mainly of Near Eastern origin but also harboured west European hunter-gatherer related ancestry. We model these populations' deep relationships and show that early European farmers had similar to 44% ancestry from a 'basal Eurasian' population that split before the diversification of other non-African lineages.

  • 231.
    Lazazzera, Beth A
    et al.
    University of California Los Angeles.
    Hughes, Diarmaid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Genetics: Location affects sporulation2015In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 525, no 7567, 42-43 p.Article in journal (Other (popular science, discussion, etc.))
    Abstract [en]

    Monitored changes in the number of copies of a gene during DNA replication control the timing of sporulation in bacteria. This discovery links replication to the concept that a gene's location on a chromosome can influence cell traits.

  • 232. Lee, Chiara
    et al.
    Kang, Hae Joo
    von Ballmoos, Christoph
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Newstead, Simon
    Uzdavinys, Povilas
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Dotson, David L.
    Iwata, So
    Beckstein, Oliver
    Cameron, Alexander D.
    Drew, David
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Imperial College London .
    A two-domain elevator mechanism for sodium/proton antiport2013In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 501, no 7468, 573-577 p.Article in journal (Refereed)
    Abstract [en]

    Sodium/proton (Na+/H+) antiporters, located at the plasma membrane in every cell, are vital for cell homeostasis1. In humans, their dysfunction has been linked to diseases, such as hypertension, heart failure and epilepsy, and they are well-established drug targets(2). The best understood model system for Na+/H+ antiport is NhaA from Escherichia coli(1,3), for which both electron microscopy and crystal structures are available(4-6). NhaA is made up of two distinct domains: a core domain and a dimerization domain. In the NhaA crystal structure a cavity is located between the two domains, providing access to the ion-binding site from the inward-facing surface of the protein(1,4). Likemany Na+/H+ antiporters, the activity of NhaA is regulated by pH, only becoming active above pH 6.5, at which point a conformational change is thought to occur(7). The only reported NhaA crystal structure so far is of the low pH inactivated form(4). Here we describe the active-state structure of a Na+/H+ antiporter, NapA from Thermus thermophilus, at 3 angstrom resolution, solved from crystals grown at pH7.8. In the NapA structure, the core and dimerization domains are in different positions to those seen in NhaA, and a negatively charged cavity has now opened to the outside. The extracellular cavity allows access to a strictly conserved aspartate residue thought to coordinate ion binding(1,8,9) directly, a role supported hereby molecular dynamics simulations. To alternate access to this ion-binding site, however, requires a surprisingly large rotation of the core domain, some 20 degrees against the dimerization interface. We conclude that despite their fast transport rates of up to 1,500 ions per second(3), Na+/H+ antiporters operate by a two-domain rocking bundle model, revealing themes relevant to secondary-active transporters in general.

  • 233. Li, X P
    et al.
    Bjorkman, O
    Shih, C
    Grossman, A R
    Rosenquist, M
    Jansson, Stefan
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Niyogi, K K
    A pigment-binding protein essential for regulation of photosynthetic light harvesting2000In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 403, no 6768, 391-395 p.Article in journal (Refereed)
    Abstract [en]

    Photosynthetic light harvesting in plants is regulated in response to changes in incident light intensity. Absorption of light that exceeds a plant's capacity for fixation of CO2 results in thermal dissipation of excitation energy in the pigment antenna of photosystem II by a poorly understood mechanism. This regulatory process, termed nonphotochemical quenching, maintains the balance between dissipation and utilization of light energy to minimize generation of oxidizing molecules, thereby protecting the plant against photo-oxidative damage. To identify specific proteins that are involved in nonphotochemical quenching, we have isolated mutants of Arabidopsis thaliana that cannot dissipate excess absorbed light energy. Here we show that the gene encoding PsbS, an intrinsic chlorophyll-binding protein of photosystem II, is necessary for nonphotochemical quenching but not for efficient light harvesting and photosynthesis, These results indicate that PsbS may be the site for nonphotochemical quenching, a finding that has implications for the functional evolution of pigment-binding proteins.

  • 234. Liang, Liming
    et al.
    Willis-Owen, Saffron A. G.
    Laprise, Catherine
    Wong, Kenny C. C.
    Davies, Gwyneth A.
    Hudson, Thomas J.
    Binia, Aristea
    Hopkin, Julian M.
    Yang, Ivana V.
    Grundberg, Elin
    Busche, Stephan
    Hudson, Marie
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Pastinen, Tomi M.
    Schwartz, David A.
    Lathrop, G. Mark
    Moffatt, Miriam F.
    Cookson, William O. C. M.
    An epigenome-wide association study of total serum immunoglobulin E concentration2015In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 520, no 7549, 670-U188 p.Article in journal (Refereed)
    Abstract [en]

    Immunoglobulin E (IgE) is a central mediator of allergic (atopic) inflammation. Therapies directed against IgE can alleviate hay fever' and allergic asthma'''. Genetic association studies have not yet identified novel therapeutic targets or pathways underlying IgE regulation'. We therefore surveyed epigenetic associations between serum IgE concentrations and methylation at loci concentrated in CpG islands genome wide in 95 nuclear pedigrees, using DNA from peripheral blood leukocytes. We validated positive results in additional families and in subjects from the general population. Here we show replicated associations with a meta-analysis false discovery rate less than 10-4 between IgE and low methylation at 36 loci. Genes annotated to these loci encode known eosinophil products, and also implicate phospholipid inflammatory mediators, specific transcription factors and mitochondrial proteins. We confirmed that methylation at these loci differed significantly in isolated eosinophils from subjects with and without asthma and high IgE levels. The top three loci accounted for 13% of IgE variation in the primary subject panel, explaining the tenfold higher variance found compared with that derived from large single-nucleotide polymorphism genome-wide association studies'''. This study identifies novel therapeutic targets and biomarkers for patient stratification for allergic diseases.

  • 235. Lien, Sigbjorn
    et al.
    Koop, Ben F.
    Sandve, Simen R.
    Miller, Jason R.
    Kent, Matthew P.
    Nome, Torfinn
    Hvidsten, Torgeir R.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Leong, Jong S.
    Minkley, David R.
    Zimin, Aleksey
    Grammes, Fabian
    Grove, Harald
    Gjuvsland, Arne
    Walenz, Brian
    Hermansen, Russell A.
    von Schalburg, Kris
    Rondeau, Eric B.
    Di Genova, Alex
    Samy, Jeevan K. A.
    Vik, Jon Olav
    Vigeland, Magnus D.
    Caler, Lis
    Grimholt, Unni
    Jentoft, Sissel
    Vage, Dag Inge
    de Jong, Pieter
    Moen, Thomas
    Baranski, Matthew
    Palti, Yniv
    Smith, Douglas R.
    Yorke, James A.
    Nederbragt, Alexander J.
    Tooming-Klunderud, Ave
    Jakobsen, Kjetill S.
    Jiang, Xuanting
    Fan, Dingding
    Liberles, David A.
    Vidal, Rodrigo
    Iturra, Patricia
    Jones, Steven J. M.
    Jonassen, Inge
    Maass, Alejandro
    Omholt, Stig W.
    Davidson, William S.
    The Atlantic salmon genome provides insights into rediploidization2016In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 533, no 7602, 200-205 p.Article in journal (Refereed)
    Abstract [en]

    The whole-genome duplication 80 million years ago of the common ancestor of salmonids (salmonid-specific fourth vertebrate whole-genome duplication, Ss4R) provides unique opportunities to learn about the evolutionary fate of a duplicated vertebrate genome in 70 extant lineages. Here we present a high-quality genome assembly for Atlantic salmon (Salmo salar), and show that large genomic reorganizations, coinciding with bursts of transposon-mediated repeat expansions, were crucial for the post-Ss4R rediploidization process. Comparisons of duplicate gene expression patterns across a wide range of tissues with orthologous genes from a pre-Ss4R outgroup unexpectedly demonstrate far more instances of neofunctionalization than subfunctionalization. Surprisingly, we find that genes that were retained as duplicates after the teleost-specific whole-genome duplication 320 million years ago were not more likely to be retained after the Ss4R, and that the duplicate retention was not influenced to a great extent by the nature of the predicted protein interactions of the gene products. Finally, we demonstrate that the Atlantic salmon assembly can serve as a reference sequence for the study of other salmonids for a range of purposes.

  • 236.
    Lindblad-Toh, Kerstin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Garber, Manuel
    Zuk, Or
    Lin, Michael F.
    Parker, Brian J.
    Washietl, Stefan
    Kheradpour, Pouya
    Ernst, Jason
    Jordan, Gregory
    Mauceli, Evan
    Ward, Lucas D.
    Lowe, Craig B.
    Holloway, Alisha K.
    Clamp, Michele
    Gnerre, Sante
    Alfoeldi, Jessica
    Beal, Kathryn
    Chang, Jean
    Clawson, Hiram
    Cuff, James
    Di Palma, Federica
    Fitzgerald, Stephen
    Flicek, Paul
    Guttman, Mitchell
    Hubisz, Melissa J.
    Jaffe, David B.
    Jungreis, Irwin
    Kent, W. James
    Kostka, Dennis
    Lara, Marcia
    Martins, Andre L.
    Massingham, Tim
    Moltke, Ida
    Raney, Brian J.
    Rasmussen, Matthew D.
    Robinson, Jim
    Stark, Alexander
    Vilella, Albert J.
    Wen, Jiayu
    Xie, Xiaohui
    Zody, Michael C.
    Worley, Kim C.
    Kovar, Christie L.
    Muzny, Donna M.
    Gibbs, Richard A.
    Warren, Wesley C.
    Mardis, Elaine R.
    Weinstock, George M.
    Wilson, Richard K.
    Birney, Ewan
    Margulies, Elliott H.
    Herrero, Javier
    Green, Eric D.
    Haussler, David
    Siepel, Adam
    Goldman, Nick
    Pollard, Katherine S.
    Pedersen, Jakob S.
    Lander, Eric S.
    Kellis, Manolis
    A high-resolution map of human evolutionary constraint using 29 mammals2011In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 478, no 7370, 476-482 p.Article in journal (Refereed)
    Abstract [en]

    The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering similar to 4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for similar to 60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate-and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease.

  • 237.
    Lindeberg, Gösta
    SIK – Svenska institutet för konserveringsforskning.
    Lævan-forming halophilic bacteria [33]1957In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 180, no 4595, 1141- p.Article in journal (Refereed)
  • 238. Locke, Adam E.
    et al.
    Kahali, Bratati
    Berndt, Sonja I.
    Justice, Anne E.
    Pers, Tune H.
    Day, Felix R.
    Powell, Corey
    Vedantam, Sailaja
    Buchkovich, Martin L.
    Yang, Jian
    Croteau-Chonka, Damien C.
    Esko, Tonu
    Fall, Tove
    Ferreira, Teresa
    Gustafsson, Stefan
    Kutalik, Zoltan
    Luan, Jian'an
    Maegi, Reedik
    Randall, Joshua C.
    Winkler, Thomas W.
    Wood, Andrew R.
    Workalemahu, Tsegaselassie
    Faul, Jessica D.
    Smith, Jennifer A.
    Zhao, Jing Hua
    Zhao, Wei
    Chen, Jin
    Fehrmann, Rudolf
    Hedman, Asa K.
    Karjalainen, Juha
    Schmidt, Ellen M.
    Absher, Devin
    Amin, Najaf
    Anderson, Denise
    Beekman, Marian
    Bolton, Jennifer L.
    Bragg-Gresham, L.
    Buyske, Steven
    Demirkan, Ayse
    Deng, Guohong
    Ehret, Georg B.
    Feenstra, Bjarke
    Feitosa, Mary F.
    Fischer, Krista
    Goel, Anuj
    Gong, Jian
    Jackson, Anne U.
    Kanoni, Stavroula
    Kleber, Marcus E.
    Kristiansson, Kati
    Lim, Unhee
    Lotay, Vaneet
    Mangino, Massimo
    Leach, Irene Mateo
    Medina-Gomez, Carolina
    Medland, Sarah E.
    Nalls, Michael A.
    Palmer, Cameron D.
    Pasko, Dorota
    Pechlivanis, Sonali
    Peters, Marjolein J.
    Prokopenko, Inga
    Shungin, Dmitry
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Odontology.
    Stancakova, Alena
    Strawbridge, Rona J.
    Sung, Yun Ju
    Tanaka, Toshiko
    Teumer, Alexander
    Trompet, Stella
    van der Laan, Sander W.
    van Settee, Jessica
    Van Vliet-Ostaptchouk, Jana V.
    Wang, Zhaoming
    Yengo, Loic
    Zhang, Weihua
    Isaacs, Aaron
    Albrecht, Eva
    Arnlov, Johan
    Arscott, Gillian M.
    Attwood, Antony P.
    Bandinelli, Stefania
    Barrett, Amy
    Bas, Isabelita N.
    Bellis, Claire
    Bennett, Amanda J.
    Berne, Christian
    Blagieva, Roza
    Blueher, Matthias
    Bohringer, Stefan
    Bonnycastle, Lori L.
    Boettcher, Yvonne
    Boyd, Heather A.
    Bruinenberg, Marcel
    Caspersen, Ida H.
    Chen, Yii-Der Ida
    Clarke, Robert
    Daw, E. Warwick
    de Craen, Anton J. M.
    Delgado, Graciela
    Dimitriou, Maria
    Doney, Alex S. F.
    Eklund, Niina
    Estrada, Karol
    Eury, Elodie
    Folkersen, Lasse
    Fraser, Ross M.
    Garcia, Melissa E.
    Geller, Frank
    Giedraitis, Vilmantas
    Gigante, Bruna
    Go, Alan S.
    Golay, Alain
    Goodall, Alison H.
    Gordon, Scott D.
    Gorski, Mathias
    Grabe, Hans-Joergen
    Grallert, Harald
    Grammer, Tanja B.
    Graessler, Jurgen
    Gronberg, Henrik
    Groves, Christopher J.
    Gusto, Gaeelle
    Haessler, Jeffrey
    Hall, Per
    Haller, Toomas
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Hartman, Catharina A.
    Hassinen, Maija
    Hayward, Caroline
    Heard-Costa, Nancy L.
    Helmer, Qinta
    Hengstenberg, Christian
    Holmen, Oddgeir
    Hottenga, Jouke-Jan
    James, Alan L.
    Jeff, Janina M.
    Johansson, Asa
    Jolley, Jennifer
    Juliusdottir, Thorhildur
    Kinnunen, Leena
    Koenig, Wolfgang
    Koskenvuo, Markku
    Kratzer, Wolfgang
    Laitinen, Jaana
    Lamina, Claudia
    Leander, Karin
    Lee, Nanette R.
    Lichtner, Peter
    Lind, Lars
    Lindstrom, Jaana
    Lo, Ken Sin
    Lobbens, Stephane
    Lorbeer, Roberto
    Lu, Yingchang
    Mach, Francois
    Magnusson, Patrik K. E.
    Mahajan, Anubha
    McArdle, Wendy L.
    McLachlan, Stela
    Menni, Cristina
    Merger, Sigrun
    Mihailov, Evelin
    Milani, Lili
    Moayyeri, Alireza
    Monda, Keri L.
    Morken, Mario A.
    Mulas, Antonella
    Mueller, Gabriele
    Mueller-Nurasyid, Martina
    Musk, Arthur W.
    Nagaraja, Ramaiah
    Noethen, Markus M.
    Nolte, Ilja M.
    Pilz, Stefan
    Rayner, Nigel W.
    Renstrom, Frida
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Rettig, Rainer
    Ried, Janina S.
    Ripke, Stephan
    Robertson, Neil R.
    Rose, Lynda M.
    Sanna, Serena
    Scharnagl, Hubert
    Scholtens, Salome
    Schumacher, Fredrick R.
    Scott, William R.
    Seufferlein, Thomas
    Shi, Jianxin
    Smith, Albert Vernon
    Smolonska, Joanna
    Stanton, Alice V.
    Steinthorsdottir, Valgerdur
    Stirrups, Kathleen
    Stringham, Heather M.
    Sundstrom, Johan
    Swertz, Morris A.
    Swift, Amy J.
    Syvanen, Ann-Christine
    Tan, Sian-Tsung
    Tayo, Bamidele O.
    Thorand, Barbara
    Thorleifsson, Gudmar
    Tyrer, Jonathan P.
    Uh, Hae-Won
    Vandenput, Liesbeth
    Verhulst, Frank C.
    Vermeulen, Sita H.
    Verweij, Niek
    Vonk, Judith M.
    Waite, Lindsay L.
    Warren, Helen R.
    Waterworth, Dawn
    Weedon, Michael N.
    Wilkens, Lynne R.
    Willenborg, Christina
    Wilsgaard, Tom
    Wojczynski, Mary K.
    Wong, Andrew
    Wrightl, Alan F.
    Zhang, Qunyuan
    Brennan, Eoin P.
    Choi, Murim
    Dastani, Zari
    Drong, Alexander W.
    Eriksson, Per
    Franco-Cereceda, Anders
    Gadin, Jesper R.
    Gharavi, Ali G.
    Goddard, Michael E.
    Handsaker, Robert E.
    Huang, Jinyan
    Karpe, Fredrik
    Kathiresan, Sekar
    Keildson, Sarah
    Kiryluk, Krzysztof
    Kubo, Michiaki
    Lee, Jong-Young
    Liang, Liming
    Lifton, Richard P.
    Ma, Baoshan
    McCarroll, Steven A.
    McKnight, Amy J.
    Min, Josine L.
    Moffatt, Miriam F.
    Montgomery, Grant W.
    Murabito, Joanne M.
    Nicholson, George
    Nyholt, Dale R.
    Okada, Yukinori
    Perry, John R. B.
    Dorajoo, Rajkumar
    Reinmaa, Eva
    Salem, Rany M.
    Sandholm, Niina
    Scott, Robert A.
    Stolk, Lisette
    Takahashi, Atsushi
    Tanaka, Toshihiro
    van 't Hooft, Ferdinand M.
    Vinkhuyzen, Anna A. E.
    Westra, Harm-Jan
    Zheng, Wei
    Zondervan, Krina T.
    Heath, Andrew C.
    Arveiler, Dominique
    Bakker, Stephan J. L.
    Beilby, John
    Bergman, Richard N.
    Blangero, John
    Bovet, Pascal
    Campbell, Harry
    Caulfield, Mark J.
    Cesana, Giancarlo
    Chakravarti, Aravinda
    Chasman, Daniel I.
    Chines, Peter S.
    Collins, Francis S.
    Crawford, Dana C.
    Cupples, L. Adrienne
    Cusi, Daniele
    Danesh, John
    de Faire, Ulf
    den Ruijter, Hester M.
    Dominiczak, Anna F.
    Erbel, Raimund
    Erdmann, Jeanette
    Eriksson, Johan G.
    Farrall, Martin
    Felix, Stephan B.
    Ferrannini, Ele
    Ferrieres, Jean
    Ford, Ian
    Forouhi, Nita G.
    Forrester, Terrence
    Franco, Oscar H.
    Gansevoort, Ron T.
    Gejman, Pablo V.
    Gieger, Christian
    Gottesman, Omri
    Gudnason, Vilmundur
    Gyllensten, Ulf
    Hall, Alistair S.
    Harris, Tamara B.
    Hattersley, Andrew T.
    Hicks, Andrew A.
    Hindorff, Lucia A.
    Hingorani, Aroon D.
    Hofman, Albert
    Homuth, Georg
    Hovingh, G. Kees
    Humphries, Steve E.
    Hunt, Steven C.
    Hypponen, Elina
    Illig, Thomas
    Jacobs, Kevin B.
    Jarvelin, Marjo-Riitta
    Joeckel, Karl-Heinz
    Johansen, Berit
    Jousilahti, Pekka
    Jukema, J. Wouter
    Jula, Antti M.
    Kaprio, Jaakko
    Kastelein, John J. P.
    Keinanen-Kiukaanniemi, Sirkka M.
    Kiemeney, Lambertus A.
    Knekt, Paul
    Kooner, Jaspal S.
    Kooperberg, Charles
    Kovacs, Peter
    Kraja, Aldi T.
    Kumari, Meena
    Kuusisto, Johanna
    Lakka, Timo A.
    Langenberg, Claudia
    Le Marchand, Laic
    Lehtimaki, Terho
    Lyssenko, Valeriya
    Mannisto, Satu
    Marette, Andre
    Matise, Tara C.
    McKenzie, Colin A.
    McKnight, Barbara
    Moll, Frans L.
    Morris, Andrew D.
    Morris, Andrew P.
    Murray, Jeffrey C.
    Nelis, Mari
    Ohlsson, Claes
    Oldehinkel, Albertine J.
    Ong, Ken K.
    Madden, Pamela A. F.
    Pasterkamp, Gerard
    Peden, John F.
    Peters, Annette
    Postma, Dirkje S.
    Pramstaller, Peter P.
    Price, Jackie F.
    Qi, Lu
    Raitakari, Olli T.
    Rankinen, Tuomo
    Rao, D. C.
    Rice, Treva K.
    Ridker, Paul M.
    Rioux, John D.
    Ritchie, Marylyn D.
    Rudan, Igor
    Salomaa, Veikko
    Samani, Nilesh J.
    Saramines, Jouko
    Sarzynski, Mark A.
    Schunkert, Heribert
    Schwarz, Peter E. H.
    Sever, Peter
    Shuldiner, Alan R.
    Sinisalo, Juha
    Stolk, Ronald P.
    Strauch, Konstantin
    Toenjes, Anke
    Tregouet, David-Alexandre
    Tremblay, Angelo
    Tremoli, Elena
    Virtamo, Jarmo
    Vohl, Marie-Claude
    Voelker, Uwe
    Waeber, Gerard
    Willemsen, Gonneke
    Witteman, Jacqueline C.
    Zillikens, M. Carola
    Adair, Linda S.
    Amouyel, Philippe
    Asselbergs, Folkert W.
    Assimes, Themistocles L.
    Bochud, Murielle
    Boehm, Bernhard O.
    Boerwinkle, Eric
    Bornstein, Stefan R.
    Bottinger, Erwin P.
    Bouchard, Claude
    Cauchi, Stephane
    Chambers, John C.
    Chanock, Stephen J.
    Cooper, Richard S.
    de Bakker, Paul I. W.
    Dedoussis, George
    Ferrucci, Luigi
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Froguel, Philippe
    Groop, Leif C.
    Haiman, Christopher A.
    Hamsten, Anders
    Hui, Jennie
    Hunter, David J.
    Hveem, Kristian
    Kaplan, Robert C.
    Kivimaki, Mika
    Kuh, Diana
    Laakso, Markku
    Liu, Yongmei
    Martin, Nicholas G.
    Maerz, Winfried
    Melbve, Mads
    Metspalu, Andres
    Moebus, Susanne
    Munroe, Patricia B.
    Njolstad, Inger
    Oostra, Ben A.
    Palmer, Colin N. A.
    Pedersen, Nancy L.
    Perola, Markus
    Perusse, Louis
    Peters, Ulrike
    Power, Chris
    Quertermous, Thomas
    Rauramaa, Rainer
    Rivadeneira, Fernando
    Saaristo, Timo E.
    Saleheen, Danish
    Sattar, Naveed
    Schadt, Eric E.
    Schlessinger, David
    Slagboom, P. Eline
    Snieder, Harold
    Spector, Tim D.
    Thorsteinsdottir, Unnu R.
    Stumvoll, Michael
    Tuomilehto, Jaakko
    Uitterlinden, Andre G.
    Uusitupa, Matti
    van der Harst, Pim
    Walker, Mark
    Wallaschofski, Henri
    Wareham, Nicholas J.
    Watkins, Hugh
    Weir, David R.
    Wichmann, H-Erich
    Wilson, James F.
    Zanen, Pieter
    Borecki, Ingrid B.
    Deloukas, Panos
    Fox, Caroline S.
    Heid, Iris M.
    O'Connell, Jeffrey R.
    Strachan, David P.
    Stefansson, Kari
    van Duijri, Cornelia M.
    Abecasis, Goncalo R.
    Franke, Lude
    Frayling, Timothy M.
    McCarthy, Mark I.
    Visscher, Peter M.
    Scherag, Andre
    Willer, Cristen J.
    Boehnke, Michael
    Mohlke, Karen L.
    Lindgren, Cecilia M.
    Beckmann, Jacques S.
    Barroso, Ines
    North, Kari E.
    Ingelsson, Erik
    Hirschhorn, Joel N.
    Loos, Ruth J. F.
    Speliotes, Elizabeth K.
    Genetic studies of body mass index yield new insights for obesity biology2015In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 518, no 7538, 197-U401 p.Article in journal (Refereed)
    Abstract [en]

    Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in upto 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 x 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for similar to 2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous systemin obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

  • 239. Locke, Adam E
    et al.
    Kahali, Bratati
    Berndt, Sonja I
    Justice, Anne E
    Pers, Tune H
    Day, Felix R
    Powell, Corey
    Vedantam, Sailaja
    Buchkovich, Martin L
    Yang, Jian
    Croteau-Chonka, Damien C
    Esko, Tonu
    Fall, Tove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ferreira, Teresa
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Kutalik, Zoltán
    Luan, Jian'an
    Mägi, Reedik
    Randall, Joshua C
    Winkler, Thomas W
    Wood, Andrew R
    Workalemahu, Tsegaselassie
    Faul, Jessica D
    Smith, Jennifer A
    Hua Zhao, Jing
    Zhao, Wei
    Chen, Jin
    Fehrmann, Rudolf
    Hedman, Åsa K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Karjalainen, Juha
    Schmidt, Ellen M
    Absher, Devin
    Amin, Najaf
    Anderson, Denise
    Beekman, Marian
    Bolton, Jennifer L
    Bragg-Gresham, Jennifer L
    Buyske, Steven
    Demirkan, Ayse
    Deng, Guohong
    Ehret, Georg B
    Feenstra, Bjarke
    Feitosa, Mary F
    Fischer, Krista
    Goel, Anuj
    Gong, Jian
    Jackson, Anne U
    Kanoni, Stavroula
    Kleber, Marcus E
    Kristiansson, Kati
    Lim, Unhee
    Lotay, Vaneet
    Mangino, Massimo
    Mateo Leach, Irene
    Medina-Gomez, Carolina
    Medland, Sarah E
    Nalls, Michael A
    Palmer, Cameron D
    Pasko, Dorota
    Pechlivanis, Sonali
    Peters, Marjolein J
    Prokopenko, Inga
    Shungin, Dmitry
    Stančáková, Alena
    Strawbridge, Rona J
    Ju Sung, Yun
    Tanaka, Toshiko
    Teumer, Alexander
    Trompet, Stella
    van der Laan, Sander W
    van Setten, Jessica
    Van Vliet-Ostaptchouk, Jana V
    Wang, Zhaoming
    Yengo, Loïc
    Zhang, Weihua
    Isaacs, Aaron
    Albrecht, Eva
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Arscott, Gillian M
    Attwood, Antony P
    Bandinelli, Stefania
    Barrett, Amy
    Bas, Isabelita N
    Bellis, Claire
    Bennett, Amanda J
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Blagieva, Roza
    Blüher, Matthias
    Böhringer, Stefan
    Bonnycastle, Lori L
    Böttcher, Yvonne
    Boyd, Heather A
    Bruinenberg, Marcel
    Caspersen, Ida H
    Ida Chen, Yii-Der
    Clarke, Robert
    Warwick Daw, E
    de Craen, Anton J M
    Delgado, Graciela
    Dimitriou, Maria
    Doney, Alex S F
    Eklund, Niina
    Estrada, Karol
    Eury, Elodie
    Folkersen, Lasse
    Fraser, Ross M
    Garcia, Melissa E
    Geller, Frank
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Gigante, Bruna
    Go, Alan S
    Golay, Alain
    Goodall, Alison H
    Gordon, Scott D
    Gorski, Mathias
    Grabe, Hans-Jörgen
    Grallert, Harald
    Grammer, Tanja B
    Gräßler, Jürgen
    Grönberg, Henrik
    Groves, Christopher J
    Gusto, Gaëlle
    Haessler, Jeffrey
    Hall, Per
    Haller, Toomas
    Hallmans, Goran
    Hartman, Catharina A
    Hassinen, Maija
    Hayward, Caroline
    Heard-Costa, Nancy L
    Helmer, Quinta
    Hengstenberg, Christian
    Holmen, Oddgeir
    Hottenga, Jouke-Jan
    James, Alan L
    Jeff, Janina M
    Johansson, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Jolley, Jennifer
    Juliusdottir, Thorhildur
    Kinnunen, Leena
    Koenig, Wolfgang
    Koskenvuo, Markku
    Kratzer, Wolfgang
    Laitinen, Jaana
    Lamina, Claudia
    Leander, Karin
    Lee, Nanette R
    Lichtner, Peter
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lindström, Jaana
    Sin Lo, Ken
    Lobbens, Stéphane
    Lorbeer, Roberto
    Lu, Yingchang
    Mach, François
    Magnusson, Patrik K E
    Mahajan, Anubha
    McArdle, Wendy L
    McLachlan, Stela
    Menni, Cristina
    Merger, Sigrun
    Mihailov, Evelin
    Milani, Lili
    Moayyeri, Alireza
    Monda, Keri L
    Morken, Mario A
    Mulas, Antonella
    Müller, Gabriele
    Müller-Nurasyid, Martina
    Musk, Arthur W
    Nagaraja, Ramaiah
    Nöthen, Markus M
    Nolte, Ilja M
    Pilz, Stefan
    Rayner, Nigel W
    Renstrom, Frida
    Rettig, Rainer
    Ried, Janina S
    Ripke, Stephan
    Robertson, Neil R
    Rose, Lynda M
    Sanna, Serena
    Scharnagl, Hubert
    Scholtens, Salome
    Schumacher, Fredrick R
    Scott, William R
    Seufferlein, Thomas
    Shi, Jianxin
    Vernon Smith, Albert
    Smolonska, Joanna
    Stanton, Alice V
    Steinthorsdottir, Valgerdur
    Stirrups, Kathleen
    Stringham, Heather M
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Swertz, Morris A
    Swift, Amy J
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Tan, Sian-Tsung
    Tayo, Bamidele O
    Thorand, Barbara
    Thorleifsson, Gudmar
    Tyrer, Jonathan P
    Uh, Hae-Won
    Vandenput, Liesbeth
    Verhulst, Frank C
    Vermeulen, Sita H
    Verweij, Niek
    Vonk, Judith M
    Waite, Lindsay L
    Warren, Helen R
    Waterworth, Dawn
    Weedon, Michael N
    Wilkens, Lynne R
    Willenborg, Christina
    Wilsgaard, Tom
    Wojczynski, Mary K
    Wong, Andrew
    Wright, Alan F
    Zhang, Qunyuan
    Brennan, Eoin P
    Choi, Murim
    Dastani, Zari
    Drong, Alexander W
    Eriksson, Per
    Franco-Cereceda, Anders
    Gådin, Jesper R
    Gharavi, Ali G
    Goddard, Michael E
    Handsaker, Robert E
    Huang, Jinyan
    Karpe, Fredrik
    Kathiresan, Sekar
    Keildson, Sarah
    Kiryluk, Krzysztof
    Kubo, Michiaki
    Lee, Jong-Young
    Liang, Liming
    Lifton, Richard P
    Ma, Baoshan
    McCarroll, Steven A
    McKnight, Amy J
    Min, Josine L
    Moffatt, Miriam F
    Montgomery, Grant W
    Murabito, Joanne M
    Nicholson, George
    Nyholt, Dale R
    Okada, Yukinori
    Perry, John R B
    Dorajoo, Rajkumar
    Reinmaa, Eva
    Salem, Rany M
    Sandholm, Niina
    Scott, Robert A
    Stolk, Lisette
    Takahashi, Atsushi
    Tanaka, Toshihiro
    Van't Hooft, Ferdinand M
    Vinkhuyzen, Anna A E
    Westra, Harm-Jan
    Zheng, Wei
    Zondervan, Krina T
    Heath, Andrew C
    Arveiler, Dominique
    Bakker, Stephan J L
    Beilby, John
    Bergman, Richard N
    Blangero, John
    Bovet, Pascal
    Campbell, Harry
    Caulfield, Mark J
    Cesana, Giancarlo
    Chakravarti, Aravinda
    Chasman, Daniel I
    Chines, Peter S
    Collins, Francis S
    Crawford, Dana C
    Adrienne Cupples, L
    Cusi, Daniele
    Danesh, John
    de Faire, Ulf
    den Ruijter, Hester M
    Dominiczak, Anna F
    Erbel, Raimund
    Erdmann, Jeanette
    Eriksson, Johan G
    Farrall, Martin
    Felix, Stephan B
    Ferrannini, Ele
    Ferrières, Jean
    Ford, Ian
    Forouhi, Nita G
    Forrester, Terrence
    Franco, Oscar H
    Gansevoort, Ron T
    Gejman, Pablo V
    Gieger, Christian
    Gottesman, Omri
    Gudnason, Vilmundur
    Gyllensten, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Hall, Alistair S
    Harris, Tamara B
    Hattersley, Andrew T
    Hicks, Andrew A
    Hindorff, Lucia A
    Hingorani, Aroon D
    Hofman, Albert
    Homuth, Georg
    Kees Hovingh, G
    Humphries, Steve E
    Hunt, Steven C
    Hyppönen, Elina
    Illig, Thomas
    Jacobs, Kevin B
    Jarvelin, Marjo-Riitta
    Jöckel, Karl-Heinz
    Johansen, Berit
    Jousilahti, Pekka
    Wouter Jukema, J
    Jula, Antti M
    Kaprio, Jaakko
    Kastelein, John J P
    Keinanen-Kiukaanniemi, Sirkka M
    Kiemeney, Lambertus A
    Knekt, Paul
    Kooner, Jaspal S
    Kooperberg, Charles
    Kovacs, Peter
    Kraja, Aldi T
    Kumari, Meena
    Kuusisto, Johanna
    Lakka, Timo A
    Langenberg, Claudia
    Le Marchand, Loic
    Lehtimäki, Terho
    Lyssenko, Valeriya
    Männistö, Satu
    Marette, André
    Matise, Tara C
    McKenzie, Colin A
    McKnight, Barbara
    Moll, Frans L
    Morris, Andrew D
    Morris, Andrew P
    Murray, Jeffrey C
    Nelis, Mari
    Ohlsson, Claes
    Oldehinkel, Albertine J
    Ong, Ken K
    Madden, Pamela A F
    Pasterkamp, Gerard
    Peden, John F
    Peters, Annette
    Postma, Dirkje S
    Pramstaller, Peter P
    Price, Jackie F
    Qi, Lu
    Raitakari, Olli T
    Rankinen, Tuomo
    Rao, D C
    Rice, Treva K
    Ridker, Paul M
    Rioux, John D
    Ritchie, Marylyn D
    Rudan, Igor
    Salomaa, Veikko
    Samani, Nilesh J
    Saramies, Jouko
    Sarzynski, Mark A
    Schunkert, Heribert
    Schwarz, Peter E H
    Sever, Peter
    Shuldiner, Alan R
    Sinisalo, Juha
    Stolk, Ronald P
    Strauch, Konstantin
    Tönjes, Anke
    Trégouët, David-Alexandre
    Tremblay, Angelo
    Tremoli, Elena
    Virtamo, Jarmo
    Vohl, Marie-Claude
    Völker, Uwe
    Waeber, Gérard
    Willemsen, Gonneke
    Witteman, Jacqueline C
    Zillikens, M Carola
    Adair, Linda S
    Amouyel, Philippe
    Asselbergs, Folkert W
    Assimes, Themistocles L
    Bochud, Murielle
    Boehm, Bernhard O
    Boerwinkle, Eric
    Bornstein, Stefan R
    Bottinger, Erwin P
    Bouchard, Claude
    Cauchi, Stéphane
    Chambers, John C
    Chanock, Stephen J
    Cooper, Richard S
    de Bakker, Paul I W
    Dedoussis, George
    Ferrucci, Luigi
    Franks, Paul W
    Froguel, Philippe
    Groop, Leif C
    Haiman, Christopher A
    Hamsten, Anders
    Hui, Jennie
    Hunter, David J
    Hveem, Kristian
    Kaplan, Robert C
    Kivimaki, Mika
    Kuh, Diana
    Laakso, Markku
    Liu, Yongmei
    Martin, Nicholas G
    März, Winfried
    Melbye, Mads
    Metspalu, Andres
    Moebus, Susanne
    Munroe, Patricia B
    Njølstad, Inger
    Oostra, Ben A
    Palmer, Colin N A
    Pedersen, Nancy L
    Perola, Markus
    Pérusse, Louis
    Peters, Ulrike
    Power, Chris
    Quertermous, Thomas
    Rauramaa, Rainer
    Rivadeneira, Fernando
    Saaristo, Timo E
    Saleheen, Danish
    Sattar, Naveed
    Schadt, Eric E
    Schlessinger, David
    Eline Slagboom, P
    Snieder, Harold
    Spector, Tim D
    Thorsteinsdottir, Unnur
    Stumvoll, Michael
    Tuomilehto, Jaakko
    Uitterlinden, André G
    Uusitupa, Matti
    van der Harst, Pim
    Walker, Mark
    Wallaschofski, Henri
    Wareham, Nicholas J
    Watkins, Hugh
    Weir, David R
    Wichmann, H-Erich
    Wilson, James F
    Zanen, Pieter
    Borecki, Ingrid B
    Deloukas, Panos
    Fox, Caroline S
    Heid, Iris M
    O'Connell, Jeffrey R
    Strachan, David P
    Stefansson, Kari
    van Duijn, Cornelia M
    Abecasis, Gonçalo R
    Franke, Lude
    Frayling, Timothy M
    McCarthy, Mark I
    Visscher, Peter M
    Scherag, André
    Willer, Cristen J
    Boehnke, Michael
    Mohlke, Karen L
    Lindgren, Cecilia M
    Beckmann, Jacques S
    Barroso, Inês
    North, Kari E
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Hirschhorn, Joel N
    Loos, Ruth J F
    Speliotes, Elizabeth K
    Genetic studies of body mass index yield new insights for obesity biology2015In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 518, no 7538, 197-206 p.Article in journal (Refereed)
    Abstract [en]

    Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10−8), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ~2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

  • 240. Locke, Adam E
    et al.
    Kahali, Bratati
    Berndt, Sonja I
    Justice, Anne E
    Pers, Tune H
    Day, Felix R
    Powell, Corey
    Vedantam, Sailaja
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Speliotes, Elizabeth K
    Genetic studies of body mass index yield new insights for obesity biology2015In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 515, no 7538, 197-206 p.Article in journal (Refereed)
    Abstract [en]

    Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in upto 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 x 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for similar to 2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous systemin obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

  • 241. Loh, N. D.
    et al.
    Hampton, C. Y.
    Martin, A. V.
    Starodub, D.
    Sierra, R. G.
    Barty, A.
    Aquila, A.
    Schulz, J.
    Lomb, L.
    Steinbrener, J.
    Shoeman, R. L.
    Kassemeyer, S.
    Bostedt, C.
    Bozek, J.
    Epp, S. W.
    Erk, B.
    Hartmann, R.
    Rolles, D.
    Rudenko, A.
    Rudek, B.
    Foucar, L.
    Kimmel, N.
    Weidenspointner, G.
    Hauser, G.
    Holl, P.
    Pedersoli, E.
    Liang, M.
    Hunter, M. M.
    Gumprecht, L.
    Coppola, N.
    Wunderer, C.
    Graafsma, H.
    Maia, F. R. N. C.
    Ekeberg, Tomas
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular biophysics.
    Hantke, Max
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular biophysics.
    Fleckenstein, H.
    Hirsemann, H.
    Nass, K.
    White, T. A.
    Tobias, H. J.
    Farquar, G. R.
    Benner, W. H.
    Hau-Riege, S. P.
    Reich, C.
    Hartmann, A.
    Soltau, H.
    Marchesini, S.
    Bajt, S.
    Barthelmess, M.
    Bucksbaum, P.
    Hodgson, K. O.
    Strueder, L.
    Ullrich, J.
    Frank, M.
    Schlichting, I.
    Chapman, H. N.
    Bogan, M. J.
    Fractal morphology, imaging and mass spectrometry of single aerosol particles in flight2012In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 486, no 7404, 513-517 p.Article in journal (Refereed)
    Abstract [en]

    The morphology of micrometre-size particulate matter is of critical importance in fields ranging from toxicology(1) to climate science(2), yet these properties are surprisingly difficult to measure in the particles' native environment. Electron microscopy requires collection of particles on a substrate(3); visible light scattering provides insufficient resolution(4); and X-ray synchrotron studies have been limited to ensembles of particles(5). Here we demonstrate an in situ method for imaging individual sub-micrometre particles to nanometre resolution in their native environment, using intense, coherent X-ray pulses from the Linac Coherent Light Source(6) free-electron laser. We introduced individual aerosol particles into the pulsed X-ray beam, which is sufficiently intense that diffraction from individual particles can be measured for morphological analysis. At the same time, ion fragments ejected from the beam were analysed using mass spectrometry, to determine the composition of single aerosol particles. Our results show the extent of internal dilation symmetry of individual soot particles subject to non-equilibrium aggregation, and the surprisingly large variability in their fractal dimensions. More broadly, our methods can be extended to resolve both static and dynamic morphology of general ensembles of disordered particles. Such general morphology has implications in topics such as solvent accessibilities in proteins(7), vibrational energy transfer by the hydrodynamic interaction of amino acids(8), and large-scale production of nanoscale structures by flame synthesis(9).

  • 242.
    Long, John A.
    et al.
    Flinders University, Adelaide, South Australia.
    Mark-Kurik, Elga
    Tallinn University of Technology.
    Johanson, Zerina
    The Natural History Museum, London.
    Lee, Michael S.Y.
    South Australian Museum, Adelaide.
    Young, Gavin C.
    Australian National University, Canberra.
    Zhu, Min
    Institute of Vertebrate Palaeontology and Palaeoanthropology, Chinese Academy of Sciences, Beijing.
    Ahlberg, Per Erik
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
    Newman, Michael
    Jones, Roger
    den Blaauwen, Jan
    University of Amsterdam.
    Choo, Brian
    Flinders University, Adelaide.
    Trinajstic, Kate
    Curtin University, Perth, Western Australia.
    Copulation in antiarch placoderms and the origin of gnathostome internal fertilization2015In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 517, no 7533, 196-199 p.Article in journal (Refereed)
    Abstract [en]

    Reproduction in jawed vertebrates (gnathostomes) involves either external or internal fertilization. It is commonly argued that internal fertilization can evolve from external, but not the reverse. Male copulatoryclaspers are present in certain placoderms, fossil jawed vertebrates retrieved as a paraphyletic segment of the gnathostome stem group in recent studies. This suggests that internal fertilization could be primitive for gnathostomes, but such a conclusion depends on demonstrating that copulation was not just a specialized feature of certain placoderm subgroups. The reproductive biology of antiarchs, consistently identified as the least crownward placoderms and thus of great interest in this context, has until now remained unknown. Here we show that certain antiarchs possessed dermal claspers in the males, while females bore paired dermal plates inferred to have facilitated copulation. These structures are not associated with pelvic fins. The clasper morphology resembles that of ptyctodonts, a more crownward placoderm group, suggesting that all placoderm claspers are homologous and that internal fertilization characterized all placoderms. This implies that external fertilization and spawning, which characterize most extant aquatic gnathostomes, must be derived from internal fertilization, even though this transformation has been thought implausible. Alternatively, the substantial morphological evidence for placoderm paraphyly must be rejected.

  • 243. Lorenzen, Eline D.
    et al.
    Nogues-Bravo, David
    Orlando, Ludovic
    Weinstock, Jaco
    Binladen, Jonas
    Marske, Katharine A.
    Ugan, Andrew
    Borregaard, Michael K.
    Gilbert, M. Thomas P.
    Nielsen, Rasmus
    Ho, Simon Y. W.
    Goebel, Ted
    Graf, Kelly E.
    Byers, David
    Stenderup, Jesper T.
    Rasmussen, Morten
    Campos, Paula F.
    Leonard, Jennifer A.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Koepfli, Klaus-Peter
    Froese, Duane
    Zazula, Grant
    Stafford, Thomas W., Jr.
    Aaris-Sorensen, Kim
    Batra, Persaram
    Haywood, Alan M.
    Singarayer, Joy S.
    Valdes, Paul J.
    Boeskorov, Gennady
    Burns, James A.
    Davydov, Sergey P.
    Haile, James
    Jenkins, Dennis L.
    Kosintsev, Pavel
    Kuznetsova, Tatyana
    Lai, Xulong
    Martin, Larry D.
    McDonald, H. Gregory
    Mol, Dick
    Meldgaard, Morten
    Munch, Kasper
    Stephan, Elisabeth
    Sablin, Mikhail
    Sommer, Robert S.
    Sipko, Taras
    Scott, Eric
    Suchard, Marc A.
    Tikhonov, Alexei
    Willerslev, Rane
    Wayne, Robert K.
    Cooper, Alan
    Hofreiter, Michael
    Sher, Andrei
    Shapiro, Beth
    Rahbek, Carsten
    Willerslev, Eske
    Species-specific responses of Late Quaternary megafauna to climate and humans2011In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 479, no 7373, 359-364 p.Article in journal (Refereed)
    Abstract [en]

    Despite decades of research, the roles of climate and humans in driving the dramatic extinctions of large-bodied mammals during the Late Quaternary period remain contentious. Here we use ancient DNA, species distribution models and the human fossil record to elucidate how climate and humans shaped the demographic history of woolly rhinoceros, woolly mammoth, wild horse, reindeer, bison and musk ox. We show that climate has been a major driver of population change over the past 50,000 years. However, each species responds differently to the effects of climatic shifts, habitat redistribution and human encroachment. Although climate change alone can explain the extinction of some species, such as Eurasian musk ox and woolly rhinoceros, a combination of climatic and anthropogenic effects appears to be responsible for the extinction of others, including Eurasian steppe bison and wild horse. We find no genetic signature or any distinctive range dynamics distinguishing extinct from surviving species, emphasizing the challenges associated with predicting future responses of extant mammals to climate and human-mediated habitat change.

  • 244.
    Los, Marek Jan
    et al.
    Institute of Biochemistry, Albert-Ludwigs-University, Hermann-Heder-Strasse 7, D79104 Freiburg im Breisgau, Germany.
    Vandecraen, M.
    Laboratory of Molecular Biology, University of Ghent, Ghent, Belgium.
    Penning, Lc
    Laboratory of Molecular Biology, University of Ghent, Ghent, Belgium.
    Schenk, H.
    Divisions of Immunochemistry § Divisions of Immunogenetics, Tumorimmunology Program, German Cancer Research Center, Heidelberg, Germany.
    Westendorp, M.
    Divisions of Immunochemistry § Divisions of Immunogenetics, Tumorimmunology Program, German Cancer Research Center, Heidelberg, Germany.
    Baeuerle, Pa
    Institute of Biochemistry, Albert-Ludwigs-University, Hermann-Heder-Strasse 7, D79104 Freiburg im Breisgau, Germany.
    Droge, W.
    Divisions of Immunochemistry § Divisions of Immunogenetics, Tumorimmunology Program, German Cancer Research Center, Heidelberg, Germany.
    Krammer, Peter
    Divisions of Immunochemistry § Divisions of Immunogenetics, Tumorimmunology Program, German Cancer Research Center, Heidelberg, Germany.
    Fiers, W.
    Laboratory of Molecular Biology, University of Ghent, Ghent, Belgium.
    Schulze-Osthoff, Klaus
    Institute of Biochemistry, Albert-Ludwigs-University, Hermann-Heder-Strasse 7, D79104 Freiburg im Breisgau, Germany.
    Requirement of an Ice/Ced-3 Protease for Fas/Apo-1-Mediated Apoptosis1995In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 375, no 6526, 81-83 p.Article in journal (Refereed)
    Abstract [en]

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

  • 245.
    Lundström, Ingemar
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Applied Physics .
    Artificial noses - Picture the smell2000In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 406, no 6797, 682-683 p.Other (Other academic)
  • 246.
    Lundström, Ingemar
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Applied Physics .
    Artificial noses: Picture the smell2000In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 406, no 6797, 682-683 p.Article, review/survey (Refereed)
    Abstract [en]

    [No abstract available]

  • 247.
    Lundström, Ingemar
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology.
    Erlandsson, Ragnar
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology.
    Frykman, Ulf
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology.
    Hedborg, Eva
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology.
    Spetz, Anita
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology.
    Sundgren, Hans
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology.
    Welin, Stefan
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology.
    Winquist, Fredrik
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology.
    Artificial 'olfactory' images from a chemical sensor using a light-pulse technique1991In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 352, no 6330, 47-50 p.Article in journal (Refereed)
    Abstract [en]

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

  • 248. Maeda, K.
    et al.
    Benetti, S.
    Stritzinger, M.
    Röpke, F. K.
    Folatelli, G.
    Sollerman, Jesper
    Stockholm University, Faculty of Science, Department of Astronomy. Stockholm University, Faculty of Science, The Oskar Klein Centre for Cosmo Particle Physics (OKC).
    Taubenberger, S.
    Nomoto, K.
    Leloudas, G.
    Hamuy, M.
    Tanaka, M.
    Mazzali, P. A.
    Elias-Rosa, N.
    An asymmetric explosion as the origin of spectral evolution diversity in type Ia supernovae2010In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 466, no 7302, 82-85 p.Article in journal (Refereed)
    Abstract [en]

    Type Ia supernovae form an observationally uniform class of stellar explosions, in that more luminous objects have smaller decline-rates. This one-parameter behaviour allows type Ia supernovae to be calibrated as cosmological `standard candles', and led to the discovery of an accelerating Universe. Recent investigations, however, have revealed that the true nature of type Ia supernovae is more complicated. Theoretically, it has been suggested that the initial thermonuclear sparks are ignited at an offset from the centre of the white-dwarf progenitor, possibly as a result of convection before the explosion. Observationally, the diversity seen in the spectral evolution of type Ia supernovae beyond the luminosity-decline-rate relation is an unresolved issue. Here we report that the spectral diversity is a consequence of random directions from which an asymmetric explosion is viewed. Our findings suggest that the spectral evolution diversity is no longer a concern when using type Ia supernovae as cosmological standard candles. Furthermore, this indicates that ignition at an offset from the centre is a generic feature of type Ia supernovae.

  • 249.
    Makarova, Tatiana L
    et al.
    Umeå University, Faculty of Science and Technology, Physics.
    Sundqvist, Bertil
    Umeå University, Faculty of Science and Technology, Physics.
    Höhne, Roland
    Esquinazi, Pablo
    Kopelevich, Yakov
    Scharff, Peter
    Davydov, Valerii A.
    Kashevarova, Ludmila S.
    Rakhmaninova, Aleksandra V.
    Magnetic Carbon2001In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 413, no 6857, 716-718 p.Article in journal (Refereed)
    Abstract [en]

    Paper retracted.

  • 250. Malavelle, Florent F.
    et al.
    Haywood, Jim M.
    Ones, Andy J.
    Gettelman, Andrew
    Larisse, Lieven C.
    Bauduin, Sophie
    Allan, Richard P.
    Karset, Inger Helene H.
    Kristjansson, Jon Egill
    Oreopoulos, Lazaros
    Ho, Nayeong C.
    Lee, Dongmin
    Bellouin, Nicolas
    Boucher, Olivier
    Grosvenor, Daniel P.
    Arslaw, Ken S. C.
    Dhomse, Sandip
    Mann, Graham W.
    Schmidt, Anja
    Coe, Hugh
    Hartley, Margaret E.
    Dalvi, Mohit
    Hill, Adrian A.
    Johnson, Ben T.
    Johnson, Colin E.
    Knight, Jeff R.
    O'Connor, Fiona M.
    Partridge, Daniel G.
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry. University of Oxford, UK.
    Stier, Philip
    Myhre, Gunnar
    Platnick, Steven
    Stephens, Graeme L.
    Takahashi, Hanii
    Thordarson, Thorvaldur
    Strong constraints on aerosol-cloud interactions from volcanic eruptions2017In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 546, no 7659, 485-491 p.Article in journal (Refereed)
    Abstract [en]

    Aerosols have a potentially large effect on climate, particularly through their interactions with clouds, but the magnitude of this effect is highly uncertain. Large volcanic eruptions produce sulfur dioxide, which in turn produces aerosols; these eruptions thus represent a natural experiment through which to quantify aerosol-cloud interactions. Here we show that the massive 2014-2015 fissure eruption in Holuhraun, Iceland, reduced the size of liquid cloud droplets-consistent with expectations-but had no discernible effect on other cloud properties. The reduction in droplet size led to cloud brightening and global-mean radiative forcing of around -0.2 watts per square metre for September to October 2014. Changes in cloud amount or cloud liquid water path, however, were undetectable, indicating that these indirect effects, and cloud systems in general, are well buffered against aerosol changes. This result will reduce uncertainties in future climate projections, because we are now able to reject results from climate models with an excessive liquid-water-path response.

2345678 201 - 250 of 451
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf