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Sökning: WFRF:(Aerts Jan) > Refereegranskat

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1.
  • Hillier, Ladeana W, et al. (författare)
  • Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution
  • 2004
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 432:7018, s. 695-716
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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2.
  • Lembrechts, Jonas J., et al. (författare)
  • Global maps of soil temperature
  • 2022
  • Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 28:9, s. 3110-3144
  • Tidskriftsartikel (refereegranskat)abstract
    • Research in global change ecology relies heavily on global climatic grids derived from estimates of air temperature in open areas at around 2 m above the ground. These climatic grids do not reflect conditions below vegetation canopies and near the ground surface, where critical ecosystem functions occur and most terrestrial species reside. Here, we provide global maps of soil temperature and bioclimatic variables at a 1-km2 resolution for 0–5 and 5–15 cm soil depth. These maps were created by calculating the difference (i.e. offset) between in situ soil temperature measurements, based on time series from over 1200 1-km2 pixels (summarized from 8519 unique temperature sensors) across all the world's major terrestrial biomes, and coarse-grained air temperature estimates from ERA5-Land (an atmospheric reanalysis by the European Centre for Medium-Range Weather Forecasts). We show that mean annual soil temperature differs markedly from the corresponding gridded air temperature, by up to 10°C (mean = 3.0 ± 2.1°C), with substantial variation across biomes and seasons. Over the year, soils in cold and/or dry biomes are substantially warmer (+3.6 ± 2.3°C) than gridded air temperature, whereas soils in warm and humid environments are on average slightly cooler (−0.7 ± 2.3°C). The observed substantial and biome-specific offsets emphasize that the projected impacts of climate and climate change on near-surface biodiversity and ecosystem functioning are inaccurately assessed when air rather than soil temperature is used, especially in cold environments. The global soil-related bioclimatic variables provided here are an important step forward for any application in ecology and related disciplines. Nevertheless, we highlight the need to fill remaining geographic gaps by collecting more in situ measurements of microclimate conditions to further enhance the spatiotemporal resolution of global soil temperature products for ecological applications.
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5.
  • Aerts, Sven, et al. (författare)
  • Two-photon Franson-type experiments and local realism
  • 1999
  • Ingår i: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 83:15, s. 2872-2876
  • Tidskriftsartikel (refereegranskat)abstract
    • The two-photon interferometric experiment proposed by J. D. Franson [Phys. Rev. Lett. 62, 2205 (1989)] is often treated as a “Bell test of local realism.” However, it has been suggested that this is incorrect due to the 50% postselection performed even in the ideal gedanken version of the experiment. Here we present a simple local hidden variable model of the experiment that successfully explains the results obtained in usual realizations of the experiment, even with perfect detectors. Furthermore, we also show that there is no such model if the switching of the local phase settings is done at a rate determined by the internal geometry of the interferometers.
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6.
  • Bogaerts, Jonathan, et al. (författare)
  • Employing complementary spectroscopies to study the conformations of an epimeric pair of side-chain stapled peptides in aqueous solution
  • 2021
  • Ingår i: RSC Advances. - : Royal Society of Chemistry. - 2046-2069. ; 11:7, s. 4200-4208
  • Tidskriftsartikel (refereegranskat)abstract
    • Understanding the conformational preferences of free ligands in solution is often necessary to rationalize structure–activity relationships in drug discovery. Herein, we examine the conformational behavior of an epimeric pair of side-chain stapled peptides that inhibit the FAD dependent amine oxidase lysine specific demethylase 1 (LSD1). The peptides differ only at a single stereocenter, but display a major difference in binding affinity. Their Raman optical activity (ROA) spectra are most likely dominated by the C-terminus, obscuring the analysis of the epimeric macrocycle. By employing NMR spectroscopy, we show a difference in conformational behavior between the two compounds and that the LSD1 bound conformation of the most potent compound is present to a measurable extent in aqueous solution. In addition, we illustrate that Molecular Dynamics (MD) simulations produce ensembles that include the most important solution conformations, but that it remains problematic to identify relevant conformations with no a priori knowledge from the large conformational pool. Furthermore, this work highlights the importance of understanding the scope and limitations of the available techniques for conducting conformational analyses. It also emphasizes the importance of conformational selection of a flexible ligand in molecular recognition.
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7.
  • Conrad, Donald F., et al. (författare)
  • Origins and functional impact of copy number variation in the human genome
  • 2010
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7289, s. 704-712
  • Tidskriftsartikel (refereegranskat)abstract
    • Structural variations of DNA greater than 1 kilobase in size account for most bases that vary among human genomes, but are still relatively under-ascertained. Here we use tiling oligonucleotide microarrays, comprising 42 million probes, to generate a comprehensive map of 11,700 copy number variations (CNVs) greater than 443 base pairs, of which most (8,599) have been validated independently. For 4,978 of these CNVs, we generated reference genotypes from 450 individuals of European, African or East Asian ancestry. The predominant mutational mechanisms differ among CNV size classes. Retrotransposition has duplicated and inserted some coding and non-coding DNA segments randomly around the genome. Furthermore, by correlation with known trait-associated single nucleotide polymorphisms (SNPs), we identified 30 loci with CNVs that are candidates for influencing disease susceptibility. Despite this, having assessed the completeness of our map and the patterns of linkage disequilibrium between CNVs and SNPs, we conclude that, for complex traits, the heritability void left by genome-wide association studies will not be accounted for by common CNVs.
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8.
  • Craddock, Nick, et al. (författare)
  • Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
  • 2010
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7289, s. 713-720
  • Tidskriftsartikel (refereegranskat)abstract
    • Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed,19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated similar to 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
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9.
  • Dahl, Maria, et al. (författare)
  • Lentiviral Gene Therapy Using Cellular Promoters Cures Type 1 Gaucher Disease in Mice
  • 2015
  • Ingår i: Molecular Therapy. - : Elsevier BV. - 1525-0016 .- 1525-0024. ; 23:5, s. 835-844
  • Tidskriftsartikel (refereegranskat)abstract
    • Gaucher disease is caused by an inherited deficiency of the enzyme glucosylceramidase. Due to the lack of a fully functional enzyme, there is progressive build-up of the lipid component glucosylceramide. Insufficient glucosylceramidase activity results in hepatosplenomegaly, cytopenias, and bone disease in patients. Gene therapy represents a future therapeutic option for patients unresponsive to enzyme replacement therapy and lacking a suitable bone marrow donor. By proof-of-principle experiments, we have previously demonstrated a reversal of symptoms in a murine disease model of type 1 Gaucher disease, using gammaretroviral vectors harboring strong viral promoters to drive glucosidase beta-acid (GBA) gene expression. To investigate whether safer vectors can correct the enzyme deficiency, we utilized self-inactivating lentiviral vectors (SIN LVs) with the GBA gene under the control of human phosphoglycerate kinase (PGK) and CD68 promoter, respectively. Here, we report prevention of, as well as reversal of, manifest disease symptoms after lentiviral gene transfer. Glucosylceramidase activity above levels required for clearance of glucosylceramide from tissues resulted in reversal of splenomegaly, reduced Gaucher cell infiltration and a restoration of hematological parameters. These findings support the use of SIN-LVs with cellular promoters in future clinical gene therapy protocols for type 1 Gaucher disease.
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