| 31. |
- Marouli, Eirini, et al.
(författare)
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Rare and low-frequency coding variants alter human adult height
- 2017
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
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Tidskriftsartikel (refereegranskat)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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| 32. |
- Mascher, Martin, et al.
(författare)
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A chromosome conformation capture ordered sequence of the barley genome
- 2017
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 544:7651, s. 427-433
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Tidskriftsartikel (refereegranskat)abstract
- Cereal grasses of the Triticeae tribe have been the major food source in temperate regions since the dawn of agriculture. Their large genomes are characterized by a high content of repetitive elements and large pericentromeric regions that are virtually devoid of meiotic recombination. Here we present a high-quality reference genome assembly for barley (Hordeum vulgare L.). We use chromosome conformation capture mapping to derive the linear order of sequences across the pericentromeric space and to investigate the spatial organization of chromatin in the nucleus at megabase resolution. The composition of genes and repetitive elements differs between distal and proximal regions. Gene family analyses reveal lineage-specific duplications of genes involved in the transport of nutrients to developing seeds and the mobilization of carbohydrates in grains. We demonstrate the importance of the barley reference sequence for breeding by inspecting the genomic partitioning of sequence variation in modern elite germplasm, highlighting regions vulnerable to genetic erosion.
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| 33. |
- Mayor, Jordan, et al.
(författare)
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Elevation alters ecosystem properties across temperate treelines globally
- 2017
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Ingår i: Nature. - : NATURE PUBLISHING GROUP. - 0028-0836 .- 1476-4687. ; 542:7639, s. 91-95
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Tidskriftsartikel (refereegranskat)abstract
- Temperature is a primary driver of the distribution of biodiversity as well as of ecosystem boundaries(1,2). Declining temperature with increasing elevation in montane systems has long been recognized as a major factor shaping plant community biodiversity, metabolic processes, and ecosystem dynamics(3,4). Elevational gradients, as thermoclines, also enable prediction of long-term ecological responses to climate warming(5-7). One of the most striking manifestations of increasing elevation is the abrupt transitions from forest to treeless alpine tundra(8). However, whether there are globally consistent above-and belowground responses to these transitions remains an open question(4). To disentangle the direct and indirect effects of temperature on ecosystem properties, here we evaluate replicate treeline ecotones in seven temperate regions of the world. We find that declining temperatures with increasing elevation did not affect tree leaf nutrient concentrations, but did reduce ground-layer community-weighted plant nitrogen, leading to the strong stoichiometric convergence of ground-layer plant community nitrogen to phosphorus ratios across all regions. Further, elevation-driven changes in plant nutrients were associated with changes in soil organic matter content and quality (carbon to nitrogen ratios) and microbial properties. Combined, our identification of direct and indirect temperature controls over plant communities and soil properties in seven contrasting regions suggests that future warming may disrupt the functional properties of montane ecosystems, particularly where plant community reorganization outpaces treeline advance.
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| 34. |
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| 35. |
- Moor, Kathrin, et al.
(författare)
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High-avidity IgA protects the intestine by enchaining growing bacteria
- 2017
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Ingår i: Nature. - : NATURE PUBLISHING GROUP. - 0028-0836 .- 1476-4687. ; 544:7651, s. 498-
-
Tidskriftsartikel (refereegranskat)abstract
- Vaccine-induced high-avidity IgA can protect against bacterial enteropathogens by directly neutralizing virulence factors or by poorly defined mechanisms that physically impede bacterial interactions with the gut tissues ('immune exclusion')(1-3). IgA-mediated cross-linking clumps bacteria in the gut lumen and is critical for protection against infection by non-typhoidal Salmonella enterica subspecies enterica serovar Typhimurium (S. Typhimurium). However, classical agglutination, which was thought to drive this process, is efficient only at high pathogen densities (>= 10(8) non-motile bacteria per gram). In typical infections, much lower densities(4,5) (10(0)-10(7) colony-forming units per gram) of rapidly dividing bacteria are present in the gut lumen. Here we show that a different physical process drives formation of clumps in vivo: IgA-mediated cross-linking enchains daughter cells, preventing their separation after division, and clumping is therefore dependent on growth. Enchained growth is effective at all realistic pathogen densities, and accelerates pathogen clearance from the gut lumen. Furthermore, IgA enchains plasmid-donor and -recipient clones into separate clumps, impeding conjugative plasmid transfer in vivo. Enchained growth is therefore a mechanism by which IgA can disarm and clear potentially invasive species from the intestinal lumen without requiring high pathogen densities, inflammation or bacterial killing. Furthermore, our results reveal an untapped potential for oral vaccines in combating the spread of antimicrobial resistance.
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| 36. |
- Naveira Garabato, Alberto C., et al.
(författare)
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Vigorous lateral export of the meltwater outflow from beneath an Antarctic ice shelf
- 2017
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 219-222
-
Tidskriftsartikel (refereegranskat)abstract
- The instability and accelerated melting of the Antarctic Ice Sheet are among the foremost elements of contemporary global climate change la. The increased freshwater output from Antarctica is important in determining sea level rise(1,3), the fate of Antarctic sea ice and its effect on the Earth's albedo(4,5), ongoing changes in global deep-ocean ventilation(3,6), and the evolution of Southern Ocean ecosystems and carbon cycling(7,8). A key uncertainty in assessing and predicting the impacts of Antarctic Ice Sheet melting concerns the vertical distribution of the exported meltwater. This is usually represented by climate-scale models(3-5,9) as a near-surface freshwater input to the ocean, yet measurements around Antarctica reveal the meltwater to be concentrated at deeper levels(10-14). Here we use observations of the turbulent properties of the meltwater outflows from beneath a rapidly melting Antarctic ice shelf to identify the mechanism responsible for the depth of the meltwater. We show that the initial ascent of the meltwater outflow from the ice shelf cavity triggers a centrifugal overturning instability that grows by extracting kinetic energy from the lateral shear of the background oceanic flow. The instability promotes vigorous lateral export, rapid dilution by turbulent mixing, and finally settling of meltwater at depth. We use an idealized ocean circulation model to show that this mechanism is relevant to a broad spectrum of Antarctic ice shelves. Our findings demonstrate that the mechanism producing meltwater at depth is a dynamically robust feature of Antarctic melting that should be incorporated into climate-scale models.
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| 37. |
- Nesbitt, Sterling J., et al.
(författare)
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The earliest bird-line archosaurs and the assembly of the dinosaur body plan
- 2017
-
Ingår i: Nature. - : NATURE PUBLISHING GROUP. - 0028-0836 .- 1476-4687. ; 544:7651, s. 484-
-
Tidskriftsartikel (refereegranskat)abstract
- The relationship between dinosaurs and other reptiles is well established(1-4), but the sequence of acquisition of dinosaurian features has been obscured by the scarcity of fossils with transitional morphologies. The closest extinct relatives of dinosaurs either have highly derived morphologies(5-7) or are known from poorly preserved(8,9) or incomplete material(10,11). Here we describe one of the stratigraphically lowest and phylogenetically earliest members of the avian stem lineage (Avemetatarsalia), Teleocrater rhadinus gen. et sp. nov., from the Middle Triassic epoch. The anatomy of T. rhadinus provides key information that unites several enigmatic taxa from across Pangaea into a previously unrecognized clade, Aphanosauria. This clade is the sister taxon of Ornithodira (pterosaurs and birds) and shortens the ghost lineage inferred at the base of Avemetatarsalia. We demonstrate that several anatomical features long thought to characterize Dinosauria and dinosauriforms evolved much earlier, soon after the bird-crocodylian split, and that the earliest avemetatarsalians retained the crocodylian-like ankle morphology and hindlimb proportions of stem archosaurs and early pseudosuchians. Early avemetatarsalians were substantially more species-rich, widely geographically distributed and morphologically diverse than previously recognized. Moreover, several early dinosauromorphs that were previously used as models to understand dinosaur origins may represent specialized forms rather than the ancestral avemetatarsalian morphology.
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| 38. |
- Nielsen, Rasmus, et al.
(författare)
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Tracing the peopling of the world through genomics
- 2017
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Ingår i: Nature. - : NATURE PUBLISHING GROUP. - 0028-0836 .- 1476-4687. ; 541:7637, s. 302-310
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Forskningsöversikt (refereegranskat)abstract
- Advances in the sequencing and the analysis of the genomes of both modern and ancient peoples have facilitated a number of breakthroughs in our understanding of human evolutionary history. These include the discovery of interbreeding between anatomically modern humans and extinct hominins; the development of an increasingly detailed description of the complex dispersal of modern humans out of Africa and their population expansion worldwide; and the characterization of many of the genetic adaptions of humans to local environmental conditions. Our interpretation of the evolutionary history and adaptation of humans is being transformed by analyses of these new genomic data.
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| 39. |
- Olmeda, David, et al.
(författare)
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Whole-body imaging of lymphovascular niches identifies pre-metastatic roles of midkine
- 2017
-
Ingår i: Nature. - : NATURE PUBLISHING GROUP. - 0028-0836 .- 1476-4687. ; 546:7660, s. 676-680
-
Tidskriftsartikel (refereegranskat)abstract
- Cutaneous melanoma is a type of cancer with an inherent potential for lymph node colonization, which is generally preceded by neolymphangiogenesis(1-3). However, sentinel lymph node removal does not necessarily extend the overall survival of patients with melanoma(4,5). Moreover, lymphatic vessels collapse and become dysfunctional as melanomas progress(6,7). Therefore, it is unclear whether (and how) lymphangiogenesis contributes to visceral metastasis. Soluble and vesicle-associated proteins secreted by tumours and/or their stroma have been proposed to condition pre-metastatic sites in patients with melanoma(8-14). Still, the identities and prognostic value of lymphangiogenic mediators remain unclear(2,14). Moreover, our understanding of lymphangiogenesis (in melanomas and other tumour types) is limited by the paucity of mouse models for live imaging of distal pre-metastatic niches(15). Injectable lymphatic tracers have been developed(7), but their limited diffusion precludes whole-body imaging at visceral sites(16). Vascular endothelial growth factor receptor 3 (VEGFR3) is an attractive 'lymphoreporter' 17 because its expression is strongly downregulated in normal adult lymphatic endothelial cells, but is activated in pathological situations such as inflammation and cancer(17,18). Here, we exploit this inducibility of VEGFR3 to engineer mouse melanoma models for whole-body imaging of metastasis generated by human cells, clinical biopsies or endogenously deregulated oncogenic pathways. This strategy revealed early induction of distal pre-metastatic niches uncoupled from lymphangiogenesis at primary lesions. Analyses of the melanoma secretome and validation in clinical specimens showed that the heparin-binding factor midkine is a systemic inducer of neo-lymphangiogenesis that defines patient prognosis. This role of midkine was linked to a paracrine activation of the mTOR pathway in lymphatic endothelial cells. These data support the use of VEGFR3 reporter mice as a 'MetAlert' discovery platform for drivers and inhibitors of metastasis.
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| 40. |
- Pangala, Sunitha R., et al.
(författare)
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Large emissions from floodplain trees close the Amazon methane budget
- 2017
-
Ingår i: Nature. - : NATURE PUBLISHING GROUP. - 0028-0836 .- 1476-4687. ; 552:7684, s. 230-
-
Tidskriftsartikel (refereegranskat)abstract
- Wetlands are the largest global source of atmospheric methane (CH4)(1), a potent greenhouse gas. However, methane emission inventories from the Amazon floodplain(2,3), the largest natural geographic source of CH4 in the tropics, consistently underestimate the atmospheric burden of CH4 determined via remote sensing and inversion modelling(4,5), pointing to a major gap in our understanding of the contribution of these ecosystems to CH4 emissions. Here we report CH4 fluxes from the stems of 2,357 individual Amazonian floodplain trees from 13 locations across the central Amazon basin. We find that escape of soil gas through wetland trees is the dominant source of regional CH4 emissions. Methane fluxes from Amazon tree stems were up to 200 times larger than emissions reported for temperate wet forests(6) and tropical peat swamp forests(7), representing the largest non-ebullitive wetland fluxes observed. Emissions from trees had an average stable carbon isotope value (delta C-13) of -66.2 +/- 6.4 per mil, consistent with a soil biogenic origin. We estimate that floodplain trees emit 15.1 +/- 1.8 to 21.2 +/- 2.5 teragrams of CH4 a year, in addition to the 20.5 +/- 5.3 teragrams a year emitted regionally from other sources. Furthermore, we provide a topdown regional estimate of CH4 emissions of 42.7 +/- 5.6 teragrams of CH4 a year for the Amazon basin, based on regular vertical lower-troposphere CH4 profiles covering the period 2010-2013. We find close agreement between our top-down and combined bottom-up estimates, indicating that large CH4 emissions from trees adapted to permanent or seasonal inundation can account for the emission source that is required to close the Amazon CH4 budget. Our findings demonstrate the importance of tree stem surfaces in mediating approximately half of all wetland CH4 emissions in the Amazon floodplain, a region that represents up to one-third of the global wetland CH4 source when trees are combined with other emission sources.
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