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- Satizabal, Claudia L., et al.
(författare)
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Genetic architecture of subcortical brain structures in 38,851 individuals
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:11, s. 1624-
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Tidskriftsartikel (refereegranskat)abstract
- Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
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- Kjær, Kurt H., et al.
(författare)
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A 2-million-year-old ecosystem in Greenland uncovered by environmental DNA
- 2022
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 612:7939, s. 283-291
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Tidskriftsartikel (refereegranskat)abstract
- Late Pliocene and Early Pleistocene epochs 3.6 to 0.8 million years ago1 had climates resembling those forecasted under future warming2. Palaeoclimatic records show strong polar amplification with mean annual temperatures of 11–19 °C above contemporary values3,4. The biological communities inhabiting the Arctic during this time remain poorly known because fossils are rare5. Here we report an ancient environmental DNA6 (eDNA) record describing the rich plant and animal assemblages of the Kap København Formation in North Greenland, dated to around two million years ago. The record shows an open boreal forest ecosystem with mixed vegetation of poplar, birch and thuja trees, as well as a variety of Arctic and boreal shrubs and herbs, many of which had not previously been detected at the site from macrofossil and pollen records. The DNA record confirms the presence of hare and mitochondrial DNA from animals including mastodons, reindeer, rodents and geese, all ancestral to their present-day and late Pleistocene relatives. The presence of marine species including horseshoe crab and green algae support a warmer climate than today. The reconstructed ecosystem has no modern analogue. The survival of such ancient eDNA probably relates to its binding to mineral surfaces. Our findings open new areas of genetic research, demonstrating that it is possible to track the ecology and evolution of biological communities from two million years ago using ancient eDNA.
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- Buts, L, et al.
(författare)
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Solving the phase problem for carbohydrate-binding proteins using selenium derivatives of their ligands : a case study involving the bacterial F17-G adhesin
- 2003
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Ingår i: Acta Crystallographica Section D. - : International Union of Crystallography (IUCr). - 2059-7983. ; 59:6, s. 1012-1015
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Tidskriftsartikel (refereegranskat)abstract
- The Escherichia coli adhesin F17-G is a carbohydrate-binding protein that allows the bacterium to attach to the intestinal epithelium of young ruminants. The structure of the 17 kDa lectin domain of F17-G was determined using the anomalous dispersion signal of a selenium-containing analogue of the monosaccharide ligand N-acetyl-D-glucosamine in which the anomeric oxygen was replaced by an Se atom. A three-wavelength MAD data set yielded good experimental phases to 2.6 Angstrom resolution. The structure was refined to 1.75 Angstrom resolution and was used to solve the structures of the ligand-free protein and the F17-G-N-acetyl-D-glucosamine complex. This selenium-carbohydrate phasing method could be of general use for determining the structures of carbohydrate-binding proteins.
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- Buts, L, et al.
(författare)
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The fimbrial adhesin F17-G of enterotoxigenic Escherichia coli has an immunoglobulin-like lectin domain that binds N-acetylglucosamine
- 2003
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Ingår i: Molecular Microbiology. - : Wiley. - 0950-382X .- 1365-2958. ; 49:3, s. 705-715
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Tidskriftsartikel (refereegranskat)abstract
- The F17-G adhesin at the tip of flexible F17 fimbriae of enterotoxigenic Escherichia coli mediates binding to N-acetyl-beta-D-glucosamine-presenting receptors on the microvilli of the intestinal epithelium of ruminants. We report the 1.7 Angstrom resolution crystal structure of the lectin domain of F17-G, both free and in complex with N-acetylglucosamine. The monosaccharide is bound on the side of the ellipsoid-shaped protein in a conserved site around which all natural variations of F17-G are clustered. A model is proposed for the interaction between F17-fimbriated E. coli and microvilli with enhanced affinity compared with the binding constant we determined for F17-G binding to N-acetylglucosamine (0.85 mM(-1)). Unexpectedly, the F17-G structure reveals that the lectin domains of the F17-G, PapGII and FimH fimbrial adhesins all share the immunoglobulin-like fold of the structural components (pilins) of their fimbriae, despite lack of any sequence identity. Fold comparisons with pilin and chaperone structures of the chaperone/usher pathway highlight the central role of the C-terminal beta-strand G of the immunoglobulin-like fold and provides new insights into pilus assembly, function and adhesion.
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- Güsten, R., et al.
(författare)
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APEX - The Atacama Pathfinder Experiment
- 2006
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Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. ; 6267 I
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Konferensbidrag (refereegranskat)abstract
- APEX, the Atacama Pathfinder Experiment, has been successfully commissioned and is in operation now. This novel submillimeter telescope is located at 5107 m altitude on Llano de Chajnantor in the Chilean High Andes, on what is considered one of the world's outstanding sites for submillimeter astronomy. The primary reflector with 12 m diameter has been carefully adjusted by means of holography. Its surface smoothness of 17-18 μm makes APEX suitable for observations up to 200 μm, through all atmospheric submm windows accessible from the ground.
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- Hodge, J. A., et al.
(författare)
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An ALMA Survey of Submillimeter Galaxies in the Extended Chandra Deep Field South: Source Catalog and Multiplicity
- 2013
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Ingår i: Astrophysical Journal. - 1538-4357 .- 0004-637X. ; 768:1
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Tidskriftsartikel (refereegranskat)abstract
- We present an Atacama Large Millimeter/submillimeter Array (ALMA) Cycle 0 survey of 126 submillimeter sources from the LABOCA ECDFS Submillimeter Survey (LESS). Our 870 mu m survey with ALMA (ALESS) has produced maps similar to 3x deeper and with a beam area similar to 200x smaller than the original LESS observations, doubling the current number of interferometrically-observed submillimeter sources. The high resolution of these maps allows us to resolve sources that were previously blended and accurately identify the origin of the submillimeter emission. We discuss the creation of the ALESS submillimeter galaxy (SMG) catalog, including the main sample of 99 SMGs and a supplementary sample of 32 SMGs. We find that at least 35% (possibly up to 50%) of the detected LABOCA sources have been resolved into multiple SMGs, and that the average number of SMGs per LESS source increases with LESS flux density. Using the (now precisely known) SMG positions, we empirically test the theoretical expectation for the uncertainty in the single-dish source positions. We also compare our catalog to the previously predicted radio/mid-infrared counterparts, finding that 45% of the ALESS SMGs were missed by this method. Our similar to 1 ''.6 resolution allows us to measure a size of similar to 9 kpc x 5 kpc for the rest-frame similar to 300 mu m emission region in one resolved SMG, implying a star formation rate surface density of 80 M-circle dot yr(-1) kpc(-2), and we constrain the emission regions in the remaining SMGs to be
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