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• 151. Gall, Christa
Stockholm University, Faculty of Science, Department of Physics. Stockholm University, Faculty of Science, The Oskar Klein Centre for Cosmo Particle Physics (OKC). University of Copenhagen, Denmark.
Rapid formation of large dust grains in the luminous supernova 2010j12014In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 511, no 7509, 326-+ p.Article in journal (Refereed)

The origin of dust in galaxies is still a mystery(1-4). The majority of the refractory elements are produced in supernova explosions, but it is unclear how and where dust grains condense and grow, and how they avoid destruction in the harsh environments of star-forming galaxies. The recent detection of 0.1 to 0.5 solar masses of dust in nearby supernova remnants(5-7) suggests in situ dust formation, while other observations reveal very little dust in supernovae in the first few years after explosion(1,8,10). Observations of the spectral evolution of the bright SN 2010j1 have been interpreted as pre-existing dust(11), dust formationlz(12,13) or no dust at all(14). Here we report the rapid (40 to 240 days) formation of dust in its dense circumstellar medium. The wavelength-dependent extinction of this dust reveals the presence of very large (exceeding one micrometre) grains, which resist destruction(15). At later times (500 to 900 days), the near-infrared thermal emission shows an accelerated growth in dust mass, marking the transition of the dust source from the circumstellar medium to the ejecta. This provides the link between the early and late dust mass evolution in supernovae with dense circumstellar media.

• 152. Gal-Yam, Avishay
Stockholm University, Faculty of Science, Department of Astronomy. Stockholm University, Faculty of Science, The Oskar Klein Centre for Cosmo Particle Physics (OKC). Stockholm University, Faculty of Science, Department of Astronomy. Stockholm University, Faculty of Science, The Oskar Klein Centre for Cosmo Particle Physics (OKC).
A Wolf-Rayet-like progenitor of SN 2013cu from spectral observations of a stellar wind2014In: Nature, ISSN 0028-0836, Vol. 509, no 7501, 471-+ p.Article in journal (Refereed)

The explosive fate of massive Wolf-Rayet stars(1) (WRSs) is a key open question in stellar physics. An appealing option is that hydrogen-deficient WRSs are the progenitors of some hydrogen-poor supernova explosions of types IIb, Ib and Ic (ref. 2). A blue object, having luminosity and colours consistent with those of some WRSs, has recently been identified in pre-explosion images at the location of a supernova of type Ib (ref. 3), but has not yet been conclusively determined to have been the progenitor. Similar work has so far only resulted in non-detections(4). Comparison of early photometric observations of type Ic supernovae with theoretical models suggests that the progenitor stars had radii of less than 1012 centimetres, as expected for some WRSs(5). The signature of WRSs, their emission line spectra, cannot be probed by such studies. Here we report the detection of strong emission lines in a spectrum of type IIb supernova 2013cu (iPTF13ast) obtained approximately 15.5 hours after explosion (by 'flash spectroscopy', which captures the effects of the supernova explosion shock breakout flash on material surrounding the progenitor star). We identify Wolf-Rayet-like wind signatures, suggesting a progenitor of the WN(h) subclass (those WRSs with winds dominated by helium and nitrogen, with traces of hydrogen). The extent of this dense wind may indicate increased mass loss from the progenitor shortly before its explosion, consistent with recent theoretical predictions(6).

• 153. Garrouste, Romain
Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Palaeobiology.
Is Strudiella a Devonian insect?: Reply2013In: Nature, ISSN 0028-0836, Vol. 494, no 7437, E4-E5 p.Article in journal (Refereed)
• 154. Garrouste, Romain
Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Palaeobiology.
A complete insect from the Late Devonian period2012In: Nature, ISSN 0028-0836, Vol. 488, no 7409, 82-85 p.Article in journal (Refereed)

After terrestrialization, the diversification of arthropods and vertebrates is thought to have occurred in two distinct phases(1), the first between the Silurian and the Frasnian stages (Late Devonian period) (425-385 million years (Myr) ago), and the second characterized by the emergence of numerous new major taxa, during the Late Carboniferous period (after 345 Myr ago). These two diversification periods bracket the depauperate vertebrate Romer's gap (360-345 Myr ago) and arthropod gap (385-325 Myr ago)(1), which could be due to preservational artefact(2,3). Although a recent molecular dating has given an age of 390 Myr for the Holometabola(4), the record of hexapods during the Early-Middle Devonian (411.5-391 Myr ago, Pragian to Givetian stages) is exceptionally sparse and based on fragmentary remains, which hinders the timing of this diversification. Indeed, although Devonian Archaeognatha are problematic(5,6), the Pragian of Scotland has given some Collembola and the incomplete insect Rhyniognatha, with its diagnostic dicondylic, metapterygotan mandibles(5,7). The oldest, definitively winged insects are from the Serpukhovian stage (latest Early Carboniferous period)(8). Here we report the first complete Late Devonian insect, which was probably a terrestrial species. Its 'orthopteroid' mandibles are of an omnivorous type, clearly not modified for a solely carnivorous diet. This discovery narrows the 45-Myr gap in the fossil record of Hexapoda, and demonstrates [GRAPHICS] further a first Devonian phase of diversification for the Hexapoda, as in vertebrates, and suggests that the Pterygota diversified before and during Romer's gap.

• 155. George, Julie
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
Comprehensive genomic profiles of small cell lung cancer2015In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 524, no 7563, 47-U73 p.Article in journal (Refereed)

We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Dex2/3. In rare cases, SCLC tumours exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumours and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer.

• 156.
University of Kalmar, School of Pure and Applied Natural Sciences.
University of Kalmar, School of Pure and Applied Natural Sciences.
Light stimulates growth of proteorhodopsin-containing marine Flavobacteria2007In: Nature, ISSN 0028-0836, Vol. 445, 210-213 p.Article in journal (Refereed)
• 157. Groenen, M. A.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Virology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
Analyses of pig genomes provide insight into porcine demography and evolution2012In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 491, no 7424, 393-398 p.Article in journal (Refereed)

For 10,000 years pigs and humans have shared a close and complex relationship. From domestication to modern breeding practices, humans have shaped the genomes of domestic pigs. Here we present the assembly and analysis of the genome sequence of a female domestic Duroc pig (Sus scrofa) and a comparison with the genomes of wild and domestic pigs from Europe and Asia. Wild pigs emerged in South East Asia and subsequently spread across Eurasia. Our results reveal a deep phylogenetic split between European and Asian wild boars approximately 1 million years ago, and a selective sweep analysis indicates selection on genes involved in RNA processing and regulation. Genes associated with immune response and olfaction exhibit fast evolution. Pigs have the largest repertoire of functional olfactory receptor genes, reflecting the importance of smell in this scavenging animal. The pig genome sequence provides an important resource for further improvements of this important livestock species, and our identification of many putative disease-causing variants extends the potential of the pig as a biomedical model.

• 158. Guan, Y.
Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
H5N1: How to track a flu virus2012In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 483, no 7391, 535-536 p.Article in journal (Refereed)
• 159.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Evolution, Limnology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Evolution, Limnology. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Evolution, Limnology. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Evolution, Limnology. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Evolution, Limnology.
Temperature-controlled organic carbon mineralization in lake sediments2010In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 466, no 7305, 478-481 p.Article in journal (Refereed)

Peatlands, soils and the ocean floor are well-recognized as sites of organic carbonaccumulation andrepresentimportant global carbon sinks(1,2). Although the annual burial of organic carbon in lakes and reservoirs exceeds that of ocean sediments(3), these inland waters are components of the global carbon cycle that receive only limited attention(4-6). Of the organic carbon that is being deposited onto the sediments, a certain proportion will be mineralized and the remainder will be buried over geological timescales. Here we assess the relationship between sediment organic carbon mineralization and temperature in a cross-system survey of boreal lakes in Sweden, and with input froma compilation of published data from awide range of lakes that differ with respect to climate, productivity and organic carbon source. We find that the mineralization of organic carbon in lake sediments exhibits a strongly positive relationship with temperature, which suggests that warmer water temperatures lead to more mineralization and less organic carbon burial. Assuming that future organic carbon delivery to the lake sediments will be similar to that under present-day conditions, we estimate that temperature increases following the latest scenarios presented by the Intergovernmental Panel on Climate Change(7) could result in a 4-27 per cent (0.9-6.4 Tg Cyr(-1)) decrease in annual organic carbon burial in boreal lakes.

• 160.
Limnology, Department of Ecology and Evolution, Uppsala University.
Linköping University, The Tema Institute, Department of Water and Environmental Studies. Linköping University, Faculty of Arts and Sciences. Limnology, Department of Ecology and Evolution, Uppsala University. Limnology, Department of Ecology and Evolution, Uppsala University. Limnology, Department of Ecology and Evolution, Uppsala University. Limnology, Department of Ecology and Evolution, Uppsala University.
Temperature-controlled organic carbon mineralization in lake sediments2010In: Nature, ISSN 0028-0836, Vol. 466, no 7305, 478-481 p.Article in journal (Other academic)

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

• 161.
Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK). Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK). Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
A zeolite family with expanding structural complexity and embedded isoreticular structures2015In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 524, 74-78 p.Article in journal (Refereed)

The prediction and synthesis of new crystal structures enable the targeted preparation of materials with desired properties. Among porous solids, this has been achieved for metal-organic frameworks(1-3), but not for the more widely applicable zeolites(4,5), where new materials are usually discovered using exploratory synthesis. Although millions of hypothetical zeolite structures have been proposed(6,7), not enough is known about their synthesis mechanism to allow any given structure to be prepared. Here we present an approach that combines structure solution with structure prediction, and inspires the targeted synthesis of new super-complex zeolites. We used electron diffraction to identify a family of related structures and to discover the structural 'coding' within them. This allowed us to determine the complex, and previously unknown, structure of zeolite ZSM-25 (ref. 8), which has the largest unit-cell volume of all known zeolites (91,554 cubic angstroms) and demonstrates selective CO2 adsorption. By extending our method, we were able to predict other members of a family of increasingly complex, but structurally related, zeolites and to synthesize two more-complex zeolites in the family, PST-20 and PST-25, with much larger cell volumes (166,988 and 275,178 cubic angstroms, respectively) and similar selective adsorption properties. Members of this family have the same symmetry, but an expanding unit cell, and are related by hitherto unrecognized structural principles; we call these family members embedded isoreticular zeolite structures.

• 162. Gupta, Kallol
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
The role of interfacial lipids in stabilizing membrane protein oligomers2017In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 541, no 7637, 421-424 p.Article in journal (Refereed)

Oligomerization of membrane proteins in response to lipid binding has a critical role in many cell-signalling pathways(1) but is often difficult to define(2) or predict(3). Here we report the development of a mass spectrometry platform to determine simultaneously the presence of interfacial lipids and oligomeric stability and to uncover how lipids act as key regulators of membrane-protein association. Evaluation of oligomeric strength for a dataset of 125 alpha-helical oligomeric membrane proteins reveals an absence of interfacial lipids in the mass spectra of 12 membrane proteins with high oligomeric stability. For the bacterial homologue of the eukaryotic biogenic transporters (LeuT(4), one of the proteins with the lowest oligomeric stability), we found a precise cohort of lipids within the dimer interface. Delipidation, mutation of lipid-binding sites or expression in cardiolipin-deficient Escherichia coli abrogated dimer formation. Molecular dynamics simulation revealed that cardiolipin acts as a bidentate ligand, bridging across subunits. Subsequently, we show that for the Vibrio splendidus sugar transporter SemiSWEET(5), another protein with low oligomeric stability, cardiolipin shifts the equilibrium from monomer to functional dimer. We hypothesized that lipids are essential for dimerization of the Na+/H+ antiporter NhaA from E. coli, which has the lowest oligomeric strength, but not for the substantially more stable homologous Thermus thermophilus protein NapA. We found that lipid binding is obligatory for dimerization of NhaA, whereas NapA has adapted to form an interface that is stable without lipids. Overall, by correlating interfacial strength with the presence of interfacial lipids, we provide a rationale for understanding the role of lipids in both transient and stable interactions within a range of a-helical membrane proteins, including G-protein-coupled receptors.

• 163.
Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Astronomy and Space Physics.
Sanctions against scientists threaten progress2009In: Nature, ISSN 0028-0836, Vol. 461, no 7265, 723-723 p.Article in journal (Refereed)
• 164.
Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Astronomy and Space Physics.
Scientists should promote co-operation, not boycott2007In: Nature, ISSN 0028-0836, Vol. 447, no 7147, 908-908 p.Article in journal (Refereed)
• 165. Haak, Wolfgang
Stockholm University, Faculty of Humanities, Department of Archaeology and Classical Studies, Archaeological Research Laboratory.
Massive migration from the steppe was a source for Indo-European languages in Europe2015In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 522, no 7555, 207-+ p.Article in journal (Refereed)

We generated genome-wide data from 69 Europeans who lived between 8,000-3,000 years ago by enriching ancient DNA libraries for a target set of almost 400,000 polymorphisms. Enrichment of these positions decreases the sequencing required for genome-wide ancient DNA analysis by a median of around 250-fold, allowing us to study an order of magnitude more individuals than previous studies(1-8) and to obtain new insights about the past. We show that the populations of Western and Far Eastern Europe followed opposite trajectories between 8,000-5,000 years ago. At the beginning of the Neolithic period in Europe, similar to 8,000-7,000 years ago, closely related groups of early farmers appeared in Germany, Hungary and Spain, different from indigenous hunter-gatherers, whereas Russia was inhabited by a distinctive population of hunter-gatherers with high affinity to a similar to 24,000-year-old Siberian(6). By similar to 6,000-5,000 years ago, farmers throughout much of Europe had more hunter-gatherer ancestry than their predecessors, but in Russia, the Yamnaya steppe herders of this time were descended not only from the preceding eastern European hunter-gatherers, but also from a population of Near Eastern ancestry. Western and Eastern Europe came into contact similar to 4,500 years ago, as the Late Neolithic Corded Ware people from Germany traced similar to 75% of their ancestry to the Yamnaya, documenting a massive migration into the heartland of Europe from its eastern periphery. This steppe ancestry persisted in all sampled central Europeans until at least similar to 3,000 years ago, and is ubiquitous in present-day Europeans. These results provide support for a steppe origin(9) of at least some of the Indo-European languages of Europe.

• 166. Haas, Brian J.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Genome sequence and analysis of the Irish potato famine pathogen Phytophthora infestans2009In: Nature, ISSN 0028-0836, Vol. 461, no 7262, 393-398 p.Article in journal (Refereed)

Phytophthora infestans is the most destructive pathogen of potato and a model organism for the oomycetes, a distinct lineage of fungus-like eukaryotes that are related to organisms such as brown algae and diatoms. As the agent of the Irish potato famine in the mid-nineteenth century, P. infestans has had a tremendous effect on human history, resulting in famine and population displacement(1). To this day, it affects world agriculture by causing the most destructive disease of potato, the fourth largest food crop and a critical alternative to the major cereal crops for feeding the world's population(1). Current annual worldwide potato crop losses due to late blight are conservatively estimated at \$6.7 billion(2). Management of this devastating pathogen is challenged by its remarkable speed of adaptation to control strategies such as genetically resistant cultivars(3,4). Here we report the sequence of the P. infestans genome, which at similar to 240 megabases (Mb) is by far the largest and most complex genome sequenced so far in the chromalveolates. Its expansion results from a proliferation of repetitive DNA accounting for similar to 74% of the genome. Comparison with two other Phytophthora genomes showed rapid turnover and extensive expansion of specific families of secreted disease effector proteins, including many genes that are induced during infection or are predicted to have activities that alter host physiology. These fast-evolving effector genes are localized to highly dynamic and expanded regions of the P. infestans genome. This probably plays a crucial part in the rapid adaptability of the pathogen to host plants and underpins its evolutionary potential.

• 167. Haas, Brian J.
KTH, School of Biotechnology (BIO), Glycoscience. KTH, School of Biotechnology (BIO), Glycoscience.
Genome sequence and analysis of the Irish potato famine pathogen Phytophthora infestans2009In: Nature, ISSN 0028-0836, Vol. 461, no 7262, 393-398 p.Article in journal (Refereed)

Phytophthora infestans is the most destructive pathogen of potato and a model organism for the oomycetes, a distinct lineage of fungus-like eukaryotes that are related to organisms such as brown algae and diatoms. As the agent of the Irish potato famine in the mid-nineteenth century, P. infestans has had a tremendous effect on human history, resulting in famine and population displacement(1). To this day, it affects world agriculture by causing the most destructive disease of potato, the fourth largest food crop and a critical alternative to the major cereal crops for feeding the world's population(1). Current annual worldwide potato crop losses due to late blight are conservatively estimated at \$6.7 billion(2). Management of this devastating pathogen is challenged by its remarkable speed of adaptation to control strategies such as genetically resistant cultivars(3,4). Here we report the sequence of the P. infestans genome, which at similar to 240 megabases (Mb) is by far the largest and most complex genome sequenced so far in the chromalveolates. Its expansion results from a proliferation of repetitive DNA accounting for similar to 74% of the genome. Comparison with two other Phytophthora genomes showed rapid turnover and extensive expansion of specific families of secreted disease effector proteins, including many genes that are induced during infection or are predicted to have activities that alter host physiology. These fast-evolving effector genes are localized to highly dynamic and expanded regions of the P. infestans genome. This probably plays a crucial part in the rapid adaptability of the pathogen to host plants and underpins its evolutionary potential.

• 168. Hagberg, Carolina E.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
Vascular endothelial growth factor B controls endothelial fatty acid uptake2010In: Nature, ISSN 0028-0836, Vol. 464, no 7290, 917-921 p.Article in journal (Refereed)

The vascular endothelial growth factors (VEGFs) are major angiogenic regulators and are involved in several aspects of endothelial cell physiology. However, the detailed role of VEGF-B in blood vessel function has remained unclear. Here we show that VEGF-B has an unexpected role in endothelial targeting of lipids to peripheral tissues. Dietary lipids present in circulation have to be transported through the vascular endothelium to be metabolized by tissue cells, a mechanism that is poorly understood. Bioinformatic analysis showed that Vegfb was tightly co-expressed with nuclear-encoded mitochondrial genes across a large variety of physiological conditions in mice, pointing to a role for VEGF-B in metabolism. VEGF-B specifically controlled endothelial uptake of fatty acids via transcriptional regulation of vascular fatty acid transport proteins. As a consequence, Vegfb(-/-) mice showed less uptake and accumulation of lipids in muscle, heart and brown adipose tissue, and instead shunted lipids to white adipose tissue. This regulation was mediated by VEGF receptor 1 and neuropilin 1 expressed by the endothelium. The co-expression of VEGF-B and mitochondrial proteins introduces a novel regulatory mechanism, whereby endothelial lipid uptake and mitochondrial lipid use are tightly coordinated. The involvement of VEGF-B in lipid uptake may open up the possibility for novel strategies to modulate pathological lipid accumulation in diabetes, obesity and cardiovascular diseases.

• 169. Handa, I. Tanya
Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
Consequences of biodiversity loss for litter decomposition across biomes2014In: Nature, ISSN 0028-0836, Vol. 509, no 7499, 218-221 p.Article in journal (Refereed)

The decomposition of dead organic matter is a major determinant of carbon and nutrient cycling in ecosystems, and of carbon fluxes between the biosphere and the atmosphere(1-3). Decomposition is driven by a vast diversity of organisms that are structured in complex food webs(2,4). Identifying the mechanisms underlying the effects of biodiversity on decomposition is critical(4-6) given the rapid loss of species worldwide and the effects of this loss on human well-being(7-9). Yet despite comprehensive syntheses of studies on how biodiversity affects litter decomposition(4-6,10), key questions remain, including when, where and how biodiversity has a role and whether general patterns and mechanisms occur across ecosystems and different functional types of organism(4,9-12). Here, in field experiments across five terrestrial and aquatic locations, ranging from the subarctic to the tropics, we show that reducing the functional diversity of decomposer organisms and plant litter types slowed the cycling of litter carbon and nitrogen. Moreover, we found evidence of nitrogen transfer from the litter of nitrogen-fixing plants to that of rapidly decomposing plants, but not between other plant functional types, highlighting that specific interactions in litter mixtures control carbon and nitrogen cycling during decomposition. The emergence of this general mechanism and the coherence of patterns across contrasting terrestrial and aquatic ecosystems suggest that biodiversity loss has consistent consequences for litter decomposition and the cycling of major elements on broad spatial scales.

• 170.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Centre for Research Ethics and Bioethics.
Biobanks: Validate gene findings before telling donors2012In: Nature, ISSN 0028-0836, Vol. 484, no 7395, 455-455 p.Article in journal (Refereed)
• 171. Hayes, Matthew
Stockholm University, Faculty of Science, Department of Astronomy. Stockholm University, Faculty of Science, The Oskar Klein Centre for Cosmo Particle Physics (OKC). Stockholm University, Faculty of Science, Department of Astronomy. Stockholm University, Faculty of Science, The Oskar Klein Centre for Cosmo Particle Physics (OKC).
Escape of about five per cent of Lyman-alpha photons from high-redshift star-forming galaxies2010In: Nature, ISSN 0028-0836, Vol. 464, no 7288, 562-565 p.Article in journal (Refereed)

The Lyman-alpha (Ly alpha) emission line is the primary observational signature of star-forming galaxies at the highest redshifts(1), and has enabled the compilation of large samples of galaxies with which to study cosmic evolution(2-5). The resonant nature of the line, however, means that Ly alpha photons scatter in the neutral interstellar medium of their host galaxies, and their sensitivity to absorption by interstellar dust may therefore be greatly enhanced. This implies that the Ly alpha luminosity may be significantly reduced, or even completely suppressed. Hitherto, no unbiased empirical test of the escaping fraction (f(esc)) of Ly alpha photons has been performed at high redshifts. Here we report that the average f(esc) from star-forming galaxies at redshift z=2.2 is just 5 per cent by performing a blind narrowband survey in Ly alpha and H alpha. This implies that numerous conclusions based on Ly alpha-selected samples will require upwards revision by an order of magnitude and we provide a benchmark for this revision. We demonstrate that almost 90 per cent of star-forming galaxies emit insufficient Ly alpha to be detected by standard selection criteria(2-5). Both samples show an anti-correlation of f(esc) with dust content, and we show that Ly alpha- and H alpha-selection recovers populations that differ substantially in dust content and f(esc).

• 172.
University of California, San Diego, USA.
University of California, San Diego, USA. University of California, San Diego, USA. University of California, San Diego, USA. Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. University of California, San Diego, USA. University of South Florida, Tampa, USA. University of California, San Diego, USA. University of California, San Diego, USA. University of Manitoba, Winnipeg, Canada. University of South Florida, Tampa, USA. Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. University of California, San Diego, USA. University of California, San Diego, USA. University of California, San Diego, USA.
A complex containing N-CoR, mSin3 and histone deacetylase mediates transcriptional repression1997In: Nature, ISSN 0028-0836, Vol. 387, no 6628, 43-48 p.Article in journal (Refereed)

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

• 173.
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
Recognition of transmembrane helices by the endoplasmic reticulum translocon2005In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 433, no 7024, 377-381 p.Article in journal (Refereed)

Membrane proteins depend on complex translocation machineries for insertion into target membranes. Although it has long been known that an abundance of nonpolar residues in transmembrane helices is the principal criterion for membrane insertion, the specific sequence-coding for transmembrane helices has not been identified. By challenging the endoplasmic reticulum Sec61 translocon with an extensive set of designed polypeptide segments, we have determined the basic features of this code, including a 'biological' hydrophobicity scale. We find that membrane insertion depends strongly on the position of polar residues within transmembrane segments, adding a new dimension to the problem of predicting transmembrane helices from amino acid sequences. Our results indicate that direct protein - lipid interactions are critical during translocon-mediated membrane insertion.

• 174.
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
Molecular code for transmembrane-helix recognition by the Sec61 translocon2007In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 450, no 7172, 1026-1030 p.Article in journal (Refereed)

Transmembrane alpha-helices in integral membrane proteins are recognized co-translationally and inserted into the membrane of the endoplasmic reticulum by the Sec61 translocon. A full quantitative description of this phenomenon, linking amino acid sequence to membrane insertion efficiency, is still lacking. Here, using in vitro translation of a model protein in the presence of dog pancreas rough microsomes to analyse a large number of systematically designed hydrophobic segments, we present a quantitative analysis of the position- dependent contribution of all 20 amino acids to membrane insertion efficiency, as well as of the effects of transmembrane segment length and flanking amino acids. The emerging picture of translocon- mediated transmembrane helix assembly is simple, with the critical sequence characteristics mirroring the physical properties of the lipid bilayer.

• 175. Hibar, Derrek P.
Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
Common genetic variants influence human subcortical brain structures2015In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 520, no 7546, 224-U216 p.Article in journal (Refereed)

The highly complex structure of the human brain is strongly shaped by genetic influences(1). Subcortical brain regions form circuits with cortical areas to coordinate movement(2), learning, memory(3) and motivation(4), and altered circuits can lead to abnormal behaviour and disease(5). To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume(5) and intracranial volume(6). These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 X 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.

• 176.
Danish Lithosphere Centre.
University of Hawaii.
Discrete alternating hotspot islands formed by interaction of magma transport and lithospheric flexure1999In: Nature, ISSN 0028-0836, Vol. 397, no 6720, 604-607 p.Article in journal (Refereed)

The large-scale geometry and age progression of many hotspot island chains, such as the Hawaiian-Emperor chain, are well explained by the steady movement of tectonic plates over stationary hotspots. But on a smaller scale, hotspot tracks are composed of discrete volcanic islands whose spacing correlates with lithospheric thickness(1). Moreover, the volcanic shields themselves are often not positioned along single lines, but in more complicated patterns, such as the dual line known as the Kea and Loa trends of the Hawaiian islands(2,3). Here we make use of the hypothesis that. island spacing is controlled by lithospheric flexure(1) to develop a simple nonlinear model coupling magma flow, which feeds volcanic growth, to the flexure caused by volcanic loads on the underlying plate. For a steady source of melt underneath a moving lithospheric plate, magma is found to reach the surface and build a chain of separate volcanic edifices with realistic spacing. If a volcano is introduced away from the axis of the chain, as might occur following a change in the direction of plate motion, the model perpetuates the asymmetry for long distances and times, thereby producing an alternating: series of edifices similar to that observed in the Kea and Loa trends of the Hawaiian island chain.

• 177.
Karolinska Institutet.
Karolinska Institutet. Stockholm University, Faculty of Humanities, Department of Philosophy.
Origin of Life1994In: Nature, ISSN 0028-0836, Vol. 371, 646- p.Article in journal (Other academic)
• 178. Hillier, Ladeana W
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Evolutionary Biology. Evolutionsbiologi. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Evolutionary Biology. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Evolutionary Biology. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Evolutionary Biology. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Evolutionary Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution2004In: Nature, ISSN 0028-0836, Vol. 432, no 7018, 695-716 p.Article in journal (Refereed)

We present here a draft genome sequence of the red jungle fowl, Gallus gallus. Because the chicken is a modern descendant of the dinosaurs and the first non-mammalian amniote to have its genome sequenced, the draft sequence of its genome--composed of approximately one billion base pairs of sequence and an estimated 20,000-23,000 genes--provides a new perspective on vertebrate genome evolution, while also improving the annotation of mammalian genomes. For example, the evolutionary distance between chicken and human provides high specificity in detecting functional elements, both non-coding and coding. Notably, many conserved non-coding sequences are far from genes and cannot be assigned to defined functional classes. In coding regions the evolutionary dynamics of protein domains and orthologous groups illustrate processes that distinguish the lineages leading to birds and mammals. The distinctive properties of avian microchromosomes, together with the inferred patterns of conserved synteny, provide additional insights into vertebrate chromosome architecture.

• 179. Hilton, Robert G.
Stockholm University, Faculty of Science, Department of Geological Sciences. Stockholm University, Faculty of Science, Department of Geological Sciences.
Erosion of organic carbon in the Arctic as a geological carbon dioxide sink2015In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 524, no 7563, 84-U162 p.Article in journal (Refereed)

Soils of the northern high latitudes store carbon over millennial timescales (thousands of years) and contain approximately double the carbon stock of the atmosphere(1-3). Warming and associated permafrost thaw can expose soil organic carbon and result in mineralization and carbon dioxide (CO2) release(4-6). However, some of this soil organic carbon may be eroded and transferred to rivers(7-9). If it escapes degradation during river transport and is buried in marine sediments, then it can contribute to a longer-term (more than ten thousand years), geological CO2 sink(8-10). Despite this recognition, the erosional flux and fate of particulate organic carbon (POC) in large rivers at high latitudes remains poorly constrained. Here, we quantify the source of POC in the Mackenzie River, the main sediment supplier to the Arctic Ocean(11,12), and assess its flux and fate. We combine measurements of radiocarbon, stable carbon isotopes and element ratios to correct for rock-derived POC10,13,14. Our samples reveal that the eroded biospheric POC has resided in the basin for millennia, with a mean radiocarbon age of 5,800 +/- 800 years, much older than the POC in large tropical rivers(13,14). From the measured biospheric POC content and variability in annual sediment yield(15), we calculate a biospheric POC flux of 2.2(-0.9)(+1.3) teragrams of carbon per year from the Mackenzie River, which is three times the CO2 drawdown by silicate weathering in this basin(16). Offshore, we find evidence for efficient terrestrial organic carbon burial over the Holocene period, suggesting that erosion of organic carbon-rich, high-latitude soils may result in an important geological CO2 sink.

• 180. Hinke, C. B.
Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Nuclear Physics.
Superallowed Gamow-Teller decay of the doubly magic nucleus 100Sn2012In: Nature, ISSN 0028-0836, Vol. 486, no 7403, 341-345 p.Article in journal (Refereed)

The shell structure of atomic nuclei is associated with 'magic numbers' and originates in the nearly independent motion of neutrons and protons in a mean potential generated by all nucleons. During beta(+)-decay, a proton transforms into a neutron in a previously not fully occupied orbital, emitting a positron-neutrino pair with either parallel or antiparallel spins, in a Gamow-Teller or Fermi transition, respectively. The transition probability, or strength, of a Gamow-Teller transition depends sensitively on the underlying shell structure and is usually distributed among many states in the neighbouring nucleus. Here we report measurements of the half-life and decay energy for the decay of Sn-100, the heaviest doubly magic nucleus with equal numbers of protons and neutrons. In the beta-decay of Sn-100, a large fraction of the strength is observable because of the large decay energy. We determine the largest Gamow-Teller strength so far measured in allowed nuclear beta-decay, establishing the 'superallowed' nature of this Gamow-Teller transition. The large strength and the low-energy states in the daughter nucleus, In-100, are well reproduced by modern, large-scale shell model calculations.

• 181. Ho, Joshua W. K.
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
Comparative analysis of metazoan chromatin organization2014In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 512, no 7515, 449-U507 p.Article in journal (Refereed)

Genome function is dynamically regulated in part by chromatin, which consists of the histones, non-histone proteins and RNA molecules that package DNA. Studies in Caenorhabditis elegans and Drosophila melanogaster have contributed substantially to our understanding of molecular mechanisms of genome function in humans, and have revealed conservation of chromatin components and mechanisms(1-3). Nevertheless, the three organisms have markedly different genome sizes, chromosome architecture and gene organization. On human and fly chromosomes, for example, pericentric heterochromatin flanks single centromeres, whereas worm chromosomes have dispersed heterochromatin-like regions enriched in the distal chromosomal 'arms', and centromeres distributed along their lengths(4,5). To systematically investigate chromatin organization and associated gene regulation across species, we generated and analysed a large collection of genome-wide chromatin data sets from cell lines and developmental stages in worm, fly and human. Here we present over 800 new data sets from our ENCODE and modENCODE consortia, bringing the total to over 1,400. Comparison of combinatorial patterns of histone modifications, nuclear lamina-associated domains, organization of large-scale topological domains, chromatin environment at promoters and enhancers, nucleosome positioning, and DNA replication patterns reveals many conserved features of chromatin organization among the three organisms. We also find notable differences in the composition and locations of repressive chromatin. These data sets and analyses provide a rich resource for comparative and species-specific investigations of chromatin composition, organization and function.

• 182. Holmström, Mats
Institutet för rymdfysik (IRF).
Energetic neutral atoms as the explanation for the high-velocity hydrogen around HD 209458b2008In: Nature, ISSN 0028-0836, Vol. 451, 970-972 p.Article in journal (Refereed)

Absorption in the stellar Lyman- $\alpha$(Ly$\alpha$) line observed during the transit of the extrasolar planet HD 209458b in front of its host star reveals high-velocity atomic hydrogen at great distances from the planet1, 2. This has been interpreted as hydrogen atoms escaping from the planet's exosphere1, 3, possibly undergoing hydrodynamic blow-off4, and being accelerated by stellar radiation pressure. Energetic neutral atoms around Solar System planets have been observed to form from charge exchange between solar wind protons and neutral hydrogen from the planetary exospheres5, 6, 7, however, and this process also should occur around extrasolar planets. Here we show that the measured transit-associated Ly$\alpha$ absorption can be explained by the interaction between the exosphere of HD 209458b and the stellar wind, and that radiation pressure alone cannot explain the observations. As the stellar wind protons are the source of the observed energetic neutral atoms, this provides a way of probing stellar wind conditions, and our model suggests a slow and hot stellar wind near HD 209458b at the time of the observations. line observed during the transit of the extrasolar planet HD 209458b in front of its host star reveals high-velocity atomic hydrogen at great distances from the planet1, 2. This has been interpreted as hydrogen atoms escaping from the planet's exosphere1, 3, possibly undergoing hydrodynamic blow-off4, and being accelerated by stellar radiation pressure. Energetic neutral atoms around Solar System planets have been observed to form from charge exchange between solar wind protons and neutral hydrogen from the planetary exospheres5, 6, 7, however, and this process also should occur around extrasolar planets. Here we show that the measured transit-associated Ly$\alpha$ absorption can be explained by the interaction between the exosphere of HD 209458b and the stellar wind, and that radiation pressure alone cannot explain the observations. As the stellar wind protons are the source of the observed energetic neutral atoms, this provides a way of probing stellar wind conditions, and our model suggests a slow and hot stellar wind near HD 209458b at the time of the observations.

• 183. Horie, Masayuki
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Endogenous non-retroviral RNA virus elements in mammalian genomes.2010In: Nature, ISSN 0028-0836, Vol. 463, no 7277, 84-87 p.Article in journal (Refereed)

Retroviruses are the only group of viruses known to have left a fossil record, in the form of endogenous proviruses, and approximately 8% of the human genome is made up of these elements. Although many other viruses, including non-retroviral RNA viruses, are known to generate DNA forms of their own genomes during replication, none has been found as DNA in the germline of animals. Bornaviruses, a genus of non-segmented, negative-sense RNA virus, are unique among RNA viruses in that they establish persistent infection in the cell nucleus. Here we show that elements homologous to the nucleoprotein (N) gene of bornavirus exist in the genomes of several mammalian species, including humans, non-human primates, rodents and elephants. These sequences have been designated endogenous Borna-like N (EBLN) elements. Some of the primate EBLNs contain an intact open reading frame (ORF) and are expressed as mRNA. Phylogenetic analyses showed that EBLNs seem to have been generated by different insertional events in each specific animal family. Furthermore, the EBLN of a ground squirrel was formed by a recent integration event, whereas those in primates must have been formed more than 40 million years ago. We also show that the N mRNA of a current mammalian bornavirus, Borna disease virus (BDV), can form EBLN-like elements in the genomes of persistently infected cultured cells. Our results provide the first evidence for endogenization of non-retroviral virus-derived elements in mammalian genomes and give novel insights not only into generation of endogenous elements, but also into a role of bornavirus as a source of genetic novelty in its host.

• 184.
Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA.
Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA. Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA; National Taiwan University, Taiwan; National Taiwan University, Taiwan. Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA; University of Porto, Portugal. Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA; University of Tokyo, Japan. Rockefeller University, NY 10065 USA. Rockefeller University, NY 10065 USA. Mem Sloan Kettering Cancer Centre, NY 10065 USA. Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA. Karolinska Institute, Sweden. Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA. Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA. Rockefeller University, NY 10065 USA. Rockefeller University, NY 10065 USA. Mem Sloan Kettering Cancer Centre, NY 10065 USA. Mem Sloan Kettering Cancer Centre, NY 10065 USA. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA. University of Calif Berkeley, CA 94720 USA. Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA. Weill Cornell Med, NY 10021 USA. Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA. Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA; Mem Sloan Kettering Cancer Centre, NY 10065 USA. Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA. Mem Sloan Kettering Cancer Centre, NY 10065 USA. Mem Sloan Kettering Cancer Centre, NY 10065 USA. Mem Sloan Kettering Cancer Centre, NY 10065 USA. Alberta Childrens Prov Gen Hospital, Canada. Columbia University, NY 10032 USA. Mem Sloan Kettering Cancer Centre, NY 10065 USA. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Linköping University, Faculty of Medicine and Health Sciences. Oslo University Hospital, Norway. Oslo University Hospital, Norway. University of Nebraska Medical Centre, NE 68198 USA. University of Nebraska Medical Centre, NE 68198 USA. Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA; University of Porto, Portugal. University of Nebraska Medical Centre, NE 68198 USA. University of Nebraska Medical Centre, NE 68198 USA. University of Nebraska Medical Centre, NE 68198 USA. University of Nebraska Medical Centre, NE 68198 USA. Mem Sloan Kettering Cancer Centre, NY 10065 USA. Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA; Mem Sloan Kettering Cancer Centre, NY 10065 USA. Oslo University Hospital, Norway; University of Oslo, Norway. University of Medical Centre, Germany. University of Medical Centre Hamburg Eppendorf, Germany. University of Penn, PA 19104 USA. University of Calif Berkeley, CA 94720 USA. University of Penn, PA 19104 USA. Princeton University, NJ 08544 USA; Rutgers Cancer Institute New Jersey, NJ 08903 USA. Mem Sloan Kettering Cancer Centre, NY 10065 USA. Fred Hutchinson Cancer Research Centre, WA 98109 USA. Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA. Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA; Spanish National Cancer Research Centre CNIO, Spain. Mem Sloan Kettering Cancer Centre, NY 10065 USA; Weill Cornell Med, NY 10021 USA. Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA; Mem Sloan Kettering Cancer Centre, NY 10065 USA.
Tumour exosome integrins determine organotropic metastasis2015In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 527, no 7578, 329-+ p.Article in journal (Refereed)

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

• 185.
Australian Natl Univ, Res Sch Astron & Astrophys, Canberra, ACT 2601, Australia..
Univ Cambridge, Inst Astron, Cambridge CB3 0HA, England.. Australian Natl Univ, Res Sch Astron & Astrophys, Canberra, ACT 2601, Australia.. Australian Natl Univ, Res Sch Astron & Astrophys, Canberra, ACT 2601, Australia.. Australian Natl Univ, Res Sch Astron & Astrophys, Canberra, ACT 2601, Australia.. Australian Natl Univ, Res Sch Astron & Astrophys, Canberra, ACT 2601, Australia.. Univ Warsaw Observ, PL-00473 Warsaw, Poland.;Ohio State Univ, Dept Astron, Columbus, OH 43210 USA.. Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Observational Astronomy. Australian Natl Univ, Res Sch Astron & Astrophys, Canberra, ACT 2601, Australia.;Univ Hertfordshire, Sch Phys Astron & Math, Ctr Astrophys Res, Hatfield AL10 9AB, Herts, England.. Australian Natl Univ, Res Sch Astron & Astrophys, Canberra, ACT 2601, Australia.. Max Planck Inst Astron, D-69117 Heidelberg, Germany.. Australian Natl Univ, Res Sch Astron & Astrophys, Canberra, ACT 2601, Australia.. Australian Natl Univ, Res Sch Astron & Astrophys, Canberra, ACT 2601, Australia.. Australian Natl Univ, Res Sch Astron & Astrophys, Canberra, ACT 2601, Australia.. Australian Natl Univ, Res Sch Astron & Astrophys, Canberra, ACT 2601, Australia.;Univ Paris 06, Univ Paris 04, F-75014 Paris, France.;CNRS, Inst Astrophys Paris, UMR 7095, F-75014 Paris, France.. Univ Warsaw Observ, PL-00473 Warsaw, Poland.. Univ Warsaw Observ, PL-00473 Warsaw, Poland.. Univ Warsaw Observ, PL-00473 Warsaw, Poland.. Univ Warsaw Observ, PL-00473 Warsaw, Poland.;Univ Concepcion, Dept Astron, Concepcion, Chile.. Univ Warsaw Observ, PL-00473 Warsaw, Poland.;Univ Warwick, Dept Phys, Coventry CV4 7AL, W Midlands, England.. Univ Warsaw Observ, PL-00473 Warsaw, Poland.. Univ Warsaw Observ, PL-00473 Warsaw, Poland.. Univ Warsaw Observ, PL-00473 Warsaw, Poland.. Univ Warsaw Observ, PL-00473 Warsaw, Poland.. Univ Warsaw Observ, PL-00473 Warsaw, Poland..
Extremely metal-poor stars from the cosmic dawn in the bulge of the Milky Way2015In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 527, no 7579, 484-487 p.Article in journal (Refereed)

The first stars are predicted to have formed within 200 million years after the Big Bang(1), initiating the cosmic dawn. A true first star has not yet been discovered, although stars(2-4) with tiny amounts of elements heavier than helium ('metals') have been found in the outer regions ('halo') of the Milky Way. The first stars and their immediate successors should, however, preferentially be found today in the central regions ('bulges') of galaxies, because they formed in the largest over-densities that grew gravitationally with time(5,6). The Milky Way bulge underwent a rapid chemical enrichment during the first 1-2 billion years(7), leading to a dearth of early, metal-poor stars(8,9). Here we report observations of extremely metal-poor stars in the Milky Way bulge, including one star with an iron abundance about 10,000 times lower than the solar value without noticeable carbon enhancement. We confirm that most of the metal-poor bulge stars are on tight orbits around the Galactic Centre, rather than being halo stars passing through the bulge, as expected for stars formed at redshifts greater than 15. Their chemical compositions are in general similar to typical halo stars of the same metallicity although intriguing differences exist, including lower abundances of carbon.

• 186.
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston MA, United States; Broad Institute of mit and Harvard, Cambridge MA, United States.
Örebro University, School of Medical Sciences. Department of Gastroenterology. Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire, United Kingdom.
Fine-mapping inflammatory bowel disease loci to single-variant resolution2017In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 547, no 7662, 173-+ p.Article in journal (Refereed)

Inflammatory bowel diseases are chronic gastrointestinal inflammatory disorders that affect millions of people worldwide. Genome-wide association studies have identified 200 inflammatory bowel disease-associated loci, but few have been conclusively resolved to specific functional variants. Here we report fine-mapping of 94 inflammatory bowel disease loci using high-density genotyping in 67,852 individuals. We pinpoint 18 associations to a single causal variant with greater than 95% certainty, and an additional 27 associations to a single variant with greater than 50% certainty. These 45 variants are significantly enriched for protein-coding changes (n = 13), direct disruption of transcription-factor binding sites (n = 3), and tissue-specific epigenetic marks (n = 10), with the last category showing enrichment in specific immune cells among associations stronger in Crohn's disease and in gut mucosa among associations stronger in ulcerative colitis. The results of this study suggest that high-resolution fine-mapping in large samples can convert many discoveries from genome-wide association studies into statistically convincing causal variants, providing a powerful substrate for experimental elucidation of disease mechanisms.

• 187. Hudson, Thomas J.
KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Biotechnology (BIO), Proteomics (closed 20130101).
International network of cancer genome projects2010In: Nature, ISSN 0028-0836, Vol. 464, no 7291, 993-998 p.Article in journal (Refereed)

The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.

• 188. Hudson, Thomas J.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
International network of cancer genome projects2010In: Nature, ISSN 0028-0836, Vol. 464, no 7291, 993-998 p.Article in journal (Refereed)

The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.

• 189. Hugot, J-P
Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, GE: gastromed. Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology.
Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease2001In: Nature, ISSN 0028-0836, Vol. 411, no 6837, 599-603 p.Article in journal (Refereed)

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

• 190. Hung, Rayjean J
Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q252008In: Nature, ISSN 0028-0836, Vol. 452, no 7187, 633-637 p.Article in journal (Refereed)

Lung cancer is the most common cause of cancer death worldwide, with over one million cases annually. To identify genetic factors that modify disease risk, we conducted a genome-wide association study by analysing 317,139 single-nucleotide polymorphisms in 1,989 lung cancer cases and 2,625 controls from six central European countries. We identified a locus in chromosome region 15q25 that was strongly associated with lung cancer (P = 9 x 10(-10)). This locus was replicated in five separate lung cancer studies comprising an additional 2,513 lung cancer cases and 4,752 controls (P = 5 x 10(-20) overall), and it was found to account for 14% (attributable risk) of lung cancer cases. Statistically similar risks were observed irrespective of smoking status or propensity to smoke tobacco. The association region contains several genes, including three that encode nicotinic acetylcholine receptor subunits (CHRNA5, CHRNA3 and CHRNB4). Such subunits are expressed in neurons and other tissues, in particular alveolar epithelial cells, pulmonary neuroendocrine cells and lung cancer cell lines, and they bind to N'-nitrosonornicotine and potential lung carcinogens. A non-synonymous variant of CHRNA5 that induces an amino acid substitution (D398N) at a highly conserved site in the second intracellular loop of the protein is among the markers with the strongest disease associations. Our results provide compelling evidence of a locus at 15q25 predisposing to lung cancer, and reinforce interest in nicotinic acetylcholine receptors as potential disease candidates and chemopreventative targets.

• 191.
Örebro University, School of Humanities, Education and Social Sciences.
United Arab Emirates Univ, Al Ain, U Arab Emirates. CUNY Hunter Coll, New York, USA; CUNY, Grad Ctr, New York, NY USA. Stanford Univ, Stanford, USA. Chinese Acad Sci, Inst Phys, Beijing, China. Rutgers State Univ, Piscataway, USA. Yale Univ, New Haven, USA. Yale Univ, New Haven, USA.
Scientists of the world speak up for equality2013In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 495, no 7439, 35-38 p.Article in journal (Refereed)

Eight experts give their prescriptions for measures that will help to close the gender gap in national from China to Sweden

• 192.
Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Theoretical Astrophysics.
Fresh light on stardust2012In: Nature, ISSN 0028-0836, Vol. 484, no 7393, 172-173 p.Article in journal (Other academic)
• 193. Högberg, Peter
Örebro University, Department of Natural Sciences.
Large-scale forest girdling shows that current photosynthesis drives soil respiration2001In: Nature, ISSN 0028-0836, Vol. 411, no 6839, 789-792 p.Article in journal (Refereed)

The respiratory activities of plant roots, of their mycorrhizal fungi and of the free-living microbial heterotrophs (decomposers) in soils are significant components of the global carbon balance, but their relative contributions remain uncertain. To separate mycorrhizal root respiration from heterotrophic respiration in a boreal pine forest, we conducted a large-scale tree-girdling experiment, comprising 9 plots each containing about 120 trees. Tree-girdling involves stripping the stem bark to the depth of the current xylem at breast height terminating the supply of current photosynthates to roots and their mycorrhizal fungi without physically disturbing the delicate root-microbe-soil system. Here we report that girdling reduced soil respiration within 1-2 months by about 54% relative to respiration on ungirdled control plots, and that decreases of up to 37% were detected within 5 days. These values clearly show that the flux of current assimilates to roots is a key driver of soil respiration; they are conservative estimates of root respiration, however, because girdling increased the use of starch reserves in the roots. Our results indicate that models of soil respiration should incorporate measures of photosynthesis and of seasonal patterns of photosynthate allocation to roots.

• 194.
University of California, San Diego, USA.
University of California, San Diego, USA. University of California, San Diego, USA. University of California, San Diego, USA. University of California, San Diego, USA. University of California, San Diego, USA. University of California, San Diego, USA. University of California, San Diego, USA. University of California, San Diego, USA. University of California, San Diego, USA. University of California, San Diego, USA.
Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressor1995In: Nature, ISSN 0028-0836, Vol. 377, no 6548, 397-404 p.Article in journal (Refereed)

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

• 195.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
Univ Helsinki, FIN-00014 Helsinki, Finland..
Norway wolf cull will hit genetic diversity2016In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 539, no 7627, 31-31 p.Article in journal (Refereed)
• 196. Ingall, Ellery D.
Role of biogenic silica in the removal of iron from the Antarctic seas2013In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 4, no 1981, 1-6 p.Article in journal (Refereed)
• 197. Jakobsson, Martin
The early Miocene onset of a ventilated circulation regime in the Arctic Ocean2007In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 447, no 7147, 986-990 p.Article in journal (Refereed)

Deep-water formation in the northern North Atlantic Ocean and the Arctic Ocean is a key driver of the global thermohaline circulation and hence also of global climate(1). Deciphering the history of the circulation regime in the Arctic Ocean has long been prevented by the lack of data from cores of Cenozoic sediments from the Arctic’s deep-sea floor. Similarly, the timing of the opening of a connection between the northern North Atlantic and the Arctic Ocean, permitting deep-water exchange, has been poorly constrained. This situation changed when the first drill cores were recovered from the central Arctic Ocean(2). Here we use these cores to show that the transition from poorly oxygenated to fully oxygenated (’ventilated’) conditions in the Arctic Ocean occurred during the later part of early Miocene times. We attribute this pronounced change in ventilation regime to the opening of the Fram Strait. A palaeo-geographic and palaeo-bathymetric reconstruction of the Arctic Ocean, together with a physical oceanographic analysis of the evolving strait and sill conditions in the Fram Strait, suggests that the Arctic Ocean went from an oxygen-poor ‘lake stage’, to a transitional ‘estuarine sea’ phase with variable ventilation, and finally to the fully ventilated ‘ocean’ phase 17.5 Myr ago. The timing of this palaeo-oceanographic change coincides with the onset of the middle Miocene climatic optimum(3), although it remains unclear if there is a causal relationship between these two events.

• 198. Jones, Felicity C.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
The genomic basis of adaptive evolution in threespine sticklebacks2012In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 484, no 7392, 55-61 p.Article in journal (Refereed)

Marine stickleback fish have colonized and adapted to thousands of streams and lakes formed since the last ice age, providing an exceptional opportunity to characterize genomic mechanisms underlying repeated ecological adaptation in nature. Here we develop a high-quality reference genome assembly for threespine sticklebacks. By sequencing the genomes of twenty additional individuals from a global set of marine and freshwater populations, we identify a genome-wide set of loci that are consistently associated with marine-freshwater divergence. Our results indicate that reuse of globally shared standing genetic variation, including chromosomal inversions, has an important role in repeated evolution of distinct marine and freshwater sticklebacks, and in the maintenance of divergent ecotypes during early stages of reproductive isolation. Both coding and regulatory changes occur in the set of loci underlying marine-freshwater evolution, but regulatory changes appear to predominate in this well known example of repeated adaptive evolution in nature.

• 199. Jones, Owen R.
Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences.
Diversity of ageing across the tree of life2014In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 505, no 7482, 169-+ p.Article in journal (Refereed)

Evolution drives, and is driven by, demography. A genotype moulds its phenotype's age patterns of mortality and fertility in an environment; these two patterns in turn determine the genotype's fitness in that environment. Hence, to understand the evolution of ageing, age patterns of mortality and reproduction need to be compared for species across the tree of life. However, few studies have done so and only for a limited range of taxa. Here we contrast standardized patterns over age for 11 mammals, 12 other vertebrates, 10 invertebrates, 12 vascular plants and a green alga. Although it has been predicted that evolution should inevitably lead to increasing mortality and declining fertility with age after maturity, there is great variation among these species, including increasing, constant, decreasing, humped and bowed trajectories for both long-and short-lived species. This diversity challenges theoreticians to develop broader perspectives on the evolution of ageing and empiricists to study the demography of more species.

• 200.
Mid Sweden University, Faculty of Science, Technology and Media, Department of Natural Sciences.
Helmholtz Centre for Environmental Research - UFZ, Leipzig, Germany. Czech University of Life Sciences, Prague, Czech Republic .
Forests: not just timber plantations2015In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 521, no 7550, 32-32 p.Article in journal (Refereed)
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