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Sökning: L773:0028 0836 OR L773:1476 4687 > (2010-2019) > (2012)

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  • Föregående 12[3]4567Nästa
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21.
  • Jones, Felicity C., et al. (författare)
  • The genomic basis of adaptive evolution in threespine sticklebacks
  • 2012
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 484:7392, s. 55-61
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>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.</p>
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22.
  • Jostins, Luke, et al. (författare)
  • Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease
  • 2012
  • Ingår i: Nature. - Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 491:7422, s. 119-124
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>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.</p>
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23.
  • Kinoshita, Masaharu, et al. (författare)
  • Genetic dissection of the circuit for hand dexterity in primates
  • 2012
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 487:7406, s. 235-U1510
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>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.</p>
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24.
  • Loh, N. D., et al. (författare)
  • Fractal morphology, imaging and mass spectrometry of single aerosol particles in flight
  • 2012
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 486:7404, s. 513-517
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>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).</p>
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25.
  • Maercker, Matthias, 1979-, et al. (författare)
  • Unexpectedly large mass loss during the thermal pulse cycle of the red giant star R Sculptoris
  • 2012
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 490:7419, s. 232-234
  • Tidskriftsartikel (refereegranskat)abstract
    • The asymptotic giant branch star R Sculptoris is surrounded by a detached shell of dust and gas. The shell originates from a thermal pulse during which the star undergoes a brief period of increased mass loss. It has hitherto been impossible to constrain observationally the timescales and mass-loss properties during and after a thermal pulse - parameters that determine the lifetime on the asymptotic giant branch and the amount of elements returned by the star. Here we report observations of CO emission from the circumstellar envelope and shell around R Sculptoris with an angular resolution of 1.3 arcsec. What was hitherto thought to be only a thin, spherical shell with a clumpy structure, is revealed to contain a spiral structure. Spiral structures associated with circumstellar envelopes have been seen previously, from which it was concluded that the systems must be binaries. Using the data, combined with hydrodynamic simulations, we conclude that R Sculptoris is a binary system that underwent a thermal pulse approximately 1800 years ago, lasting approximately 200 years. About 0.003 Msun of mass was ejected at a velocity of 14.3 km s-1 and at a rate approximately 30 times higher than the prepulse mass-loss rate. This shows that approximately 3 times more mass is returned to the interstellar medium during and immediately after a pulse than previously thought.
26.
  • Mutreja, Ankur, et al. (författare)
  • Evidence for several waves of global transmission in the seventh cholera pandemic.
  • 2012
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 477:7365, s. 462-465
  • Tidskriftsartikel (refereegranskat)abstract
    • Vibrio cholerae is a globally important pathogen that is endemic in many areas of the world and causes 3-5 million reported cases of cholera every year. Historically, there have been seven acknowledged cholera pandemics; recent outbreaks in Zimbabwe and Haiti are included in the seventh and ongoing pandemic. Only isolates in serogroup O1 (consisting of two biotypes known as 'classical' and 'El Tor') and the derivative O139 can cause epidemic cholera. It is believed that the first six cholera pandemics were caused by the classical biotype, but El Tor has subsequently spread globally and replaced the classical biotype in the current pandemic. Detailed molecular epidemiological mapping of cholera has been compromised by a reliance on sub-genomic regions such as mobile elements to infer relationships, making El Tor isolates associated with the seventh pandemic seem superficially diverse. To understand the underlying phylogeny of the lineage responsible for the current pandemic, we identified high-resolution markers (single nucleotide polymorphisms; SNPs) in 154 whole-genome sequences of globally and temporally representative V. cholerae isolates. Using this phylogeny, we show here that the seventh pandemic has spread from the Bay of Bengal in at least three independent but overlapping waves with a common ancestor in the 1950s, and identify several transcontinental transmission events. Additionally, we show how the acquisition of the SXT family of antibiotic resistance elements has shaped pandemic spread, and show that this family was first acquired at least ten years before its discovery in V. cholerae.
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29.
  • Pälike, Heiko, et al. (författare)
  • A Cenozoic record of the equatorial Pacific carbonate compensation depth
  • 2012
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 488:7413, s. 609-614
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Atmospheric carbon dioxide concentrations and climate are regulated on geological timescales by the balance between carbon input from volcanic and metamorphic outgassing and its removal by weathering feedbacks; these feedbacks involve the erosion of silicate rocks and organic-carbon-bearing rocks. The integrated effect of these processes is reflected in the calcium carbonate compensation depth, which is the oceanic depth at which calcium carbonate is dissolved. Here we present a carbonate accumulation record that covers the past 53 million years from a depth transect in the equatorial Pacific Ocean. The carbonate compensation depth tracks long-term ocean cooling, deepening from 3.0-3.5 kilometres during the early Cenozoic (approximately 55 million years ago) to 4.6 kilometres at present, consistent with an overall Cenozoic increase in weathering. We find large superimposed fluctuations in carbonate compensation depth during the middle and late Eocene. Using Earth system models, we identify changes in weathering and the mode of organic-carbon delivery as two key processes to explain these large-scale Eocene fluctuations of the carbonate compensation depth.</p>
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30.
  • Rollauer, Sarah E., et al. (författare)
  • Structure of the TatC core of the twin-arginine protein transport system
  • 2012
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 492:7428, s. 210-
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>The twin-arginine translocation (Tat) pathway is one of two general protein transport systems found in the prokaryotic cytoplasmic membrane and is conserved in the thylakoid membrane of plant chloroplasts. The defining, and highly unusual, property of the Tat pathway is that it transports folded proteins, a task that must be achieved without allowing appreciable ion leakage across the membrane. The integral membrane TatC protein is the central component of the Tat pathway. TatC captures substrate proteins by binding their signal peptides. TatC then recruits TatA family proteins to form the active translocation complex. Here we report the crystal structure of TatC from the hyperthermophilic bacterium Aquifex aeolicus. This structure provides a molecular description of the core of the Tat translocation system and a framework for understanding the unique Tat transport mechanism.</p>
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