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Sökning: WFRF:(Rusch S)

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  • Waszak, S. M., et al. (författare)
  • Germline Elongator mutations in Sonic Hedgehog medulloblastoma
  • 2020
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 580:7803, s. 396-
  • Tidskriftsartikel (refereegranskat)abstract
    • Cancer genomics has revealed many genes and core molecular processes that contribute to human malignancies, but the genetic and molecular bases of many rare cancers remains unclear. Genetic predisposition accounts for 5 to 10% of cancer diagnoses in children(1,2), and genetic events that cooperate with known somatic driver events are poorly understood. Pathogenic germline variants in established cancer predisposition genes have been recently identified in 5% of patients with the malignant brain tumour medulloblastoma(3). Here, by analysing all protein-coding genes, we identify and replicate rare germline loss-of-function variants across ELP1 in 14% of paediatric patients with the medulloblastoma subgroup Sonic Hedgehog (MBSHH). ELP1 was the most common medulloblastoma predisposition gene and increased the prevalence of genetic predisposition to 40% among paediatric patients with MBSHH. Parent-offspring and pedigree analyses identified two families with a history of paediatric medulloblastoma. ELP1-associated medulloblastomas were restricted to the molecular SHH alpha subtype(4) and characterized by universal biallelic inactivation of ELP1 owing to somatic loss of chromosome arm 9q. Most ELP1-associated medulloblastomas also exhibited somatic alterations in PTCH1, which suggests that germline ELP1 loss-of-function variants predispose individuals to tumour development in combination with constitutive activation of SHH signalling. ELP1 is the largest subunit of the evolutionarily conserved Elongator complex, which catalyses translational elongation through tRNA modifications at the wobble (U-34) position(5,6). Tumours from patients with ELP1-associated MBSHH were characterized by a destabilized Elongator complex, loss of Elongator-dependent tRNA modifications, codon-dependent translational reprogramming, and induction of the unfolded protein response, consistent with loss of protein homeostasis due to Elongator deficiency in model systems(7-9). Thus, genetic predisposition to proteome instability may be a determinant in the pathogenesis of paediatric brain cancers. These results support investigation of the role of protein homeostasis in other cancer types and potential for therapeutic interference.
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  • Kattge, Jens, et al. (författare)
  • TRY plant trait database - enhanced coverage and open access
  • 2020
  • Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
  • Tidskriftsartikel (refereegranskat)abstract
    • Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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  • Dupont, C. L., et al. (författare)
  • Functional Tradeoffs Underpin Salinity-Driven Divergence in Microbial Community Composition
  • 2014
  • Ingår i: Plos One. - 1932-6203. ; 9:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Bacterial community composition and functional potential change subtly across gradients in the surface ocean. In contrast, while there are significant phylogenetic divergences between communities from freshwater and marine habitats, the underlying mechanisms to this phylogenetic structuring yet remain unknown. We hypothesized that the functional potential of natural bacterial communities is linked to this striking divide between microbiomes. To test this hypothesis, metagenomic sequencing of microbial communities along a 1,800 km transect in the Baltic Sea area, encompassing a continuous natural salinity gradient from limnic to fully marine conditions, was explored. Multivariate statistical analyses showed that salinity is the main determinant of dramatic changes in microbial community composition, but also of large scale changes in core metabolic functions of bacteria. Strikingly, genetically and metabolically different pathways for key metabolic processes, such as respiration, biosynthesis of quinones and isoprenoids, glycolysis and osmolyte transport, were differentially abundant at high and low salinities. These shifts in functional capacities were observed at multiple taxonomic levels and within dominant bacterial phyla, while bacteria, such as SAR11, were able to adapt to the entire salinity gradient. We propose that the large differences in central metabolism required at high and low salinities dictate the striking divide between freshwater and marine microbiomes, and that the ability to inhabit different salinity regimes evolved early during bacterial phylogenetic differentiation. These findings significantly advance our understanding of microbial distributions and stress the need to incorporate salinity in future climate change models that predict increased levels of precipitation and a reduction in salinity.
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  • Sagova-Mareckova, M., et al. (författare)
  • Expanding ecological assessment by integrating microorganisms into routine freshwater biomonitoring
  • 2021
  • Ingår i: Water Research. - : Elsevier. - 0043-1354. ; 191
  • Forskningsöversikt (refereegranskat)abstract
    • Bioindication has become an indispensable part of water quality monitoring in most countries of the world, with the presence and abundance of bioindicator taxa, mostly multicellular eukaryotes, used for biotic indices. In contrast, microbes (bacteria, archaea and protists) are seldom used as bioindicators in routine assessments, although they have been recognized for their importance in environmental processes. Recently, the use of molecular methods has revealed unexpected diversity within known functional groups and novel metabolic pathways that are particularly important in energy and nutrient cycling. In various habitats, microbial communities respond to eutrophication, metals, and natural or anthropogenic organic pollutants through changes in diversity and function. In this review, we evaluated the common trends in these changes, documenting that they have value as bioindicators and can be used not only for monitoring but also for improving our understanding of the major processes in lotic and lentic environments. Current knowledge provides a solid foundation for exploiting microbial taxa, community structures and diversity, as well as functional genes, in novel monitoring programs. These microbial community measures can also be combined into biotic indices, improving the resolution of individual bioindicators. Here, we assess particular molecular approaches complemented by advanced bioinformatic analysis, as these are the most promising with respect to detailed bioindication value. We conclude that microbial community dynamics are a missing link important for our understanding of rapid changes in the structure and function of aquatic ecosystems, and should be addressed in the future environmental monitoring of freshwater ecosystems.
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  • Birkhofer, Klaus, et al. (författare)
  • A framework to identify indicator species for ecosystem services in agricultural landscapes
  • 2018
  • Ingår i: Ecological Indicators. - : Elsevier. - 1470-160X .- 1872-7034. ; 91, s. 278-286
  • Tidskriftsartikel (refereegranskat)abstract
    • Improving our understanding of the relationships between biodiversity and the delivery of ecosystem services is crucial for the development of sustainable agriculture. We introduce a novel framework that is based on the identification of indicator species for single or multiple ecosystem services across taxonomic groups based on indicator species analyses. We utilize multi-species community data (unlike previous single species approaches) without giving up information about the identity of species in our framework (unlike previous species richness approaches). We compiled a comprehensive community dataset including abundances of 683 invertebrate, vertebrate and plant species to identify indicator species that were either positively or negatively related to biological control, diversity of red-listed species or crop yield in agricultural landscapes in southern Sweden. Our results demonstrate that some taxonomic groups include significantly higher percentages of indicator species for these ecosystem services. Spider communities for example included a higher percentage of significant positive indicator species for biological control than ground or rove beetle communities. Bundles of indicator species for the analysed ecosystem service potentials usually included species that could be linked to the respective ecosystem service based on their functional role in local communities. Several of these species are conspicuous enough to be monitored by trained amateurs and could be used in bundles that are either crucial for the provision of individual ecosystem services or indicate agricultural landscapes with high value for red-listed species or crop yields. The use of bundles of characteristic indicator species for the simultaneous assessment of ecosystem services may reduce the amount of labour, time and cost in future assessments. In addition, future analysis using our framework in other ecosystems or with other subsets of ecosystem services and taxonomic groups will improve our understanding of service-providing species in local communities. In any case, expert knowledge is needed to select species from the identified subsets of significant indicator species and these species should be validated by existing data or additional sampling prior to being used for ecosystem service monitoring.
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  • Birkhofer, Klaus, et al. (författare)
  • Relationships between multiple biodiversity components and ecosystem services along a landscape complexity gradient
  • 2018
  • Ingår i: Biological Conservation. - : Elsevier. - 0006-3207 .- 1873-2917. ; 218, s. 247-253
  • Tidskriftsartikel (refereegranskat)abstract
    • The assessment of effects of anthropogenic disturbance on biodiversity (BD) and ecosystem services (ES) and their relationships are key priorities of the Intergovernmental Panel for Biodiversity and Ecosystem Services. Agricultural landscapes and their associated BD provide multiple ES and it is crucial to understand how relationships between ES and BD components change along gradients of landscape complexity. In this study, we related eight ES potentials to the species richness of five invertebrate, vertebrate and plant taxonomic groups in cereal farming systems. The landscape complexity gradient ranged from areas dominated by annually tilled arable land to areas with high proportions of unfertilized, non-rotational pastures and uncultivated field borders. We show that after accounting for landscape complexity relationships between yield and bird richness or biological control became more positive, but relationships between bird richness and biological control became less positive. The relationship between bird and plant richness turned from positive to negative. Multidiversity (overall biodiversity), was positively related to landscape complexity, whereas multifunctionality (overall ES provision), was not significantly related to either one of these. Our results suggest that multidiversity can be promoted by increasing landscape complexity; however; we found no support for a simultaneous increase of several individual ES, BD components or multifunctionality. These results challenge the assumption that biodiversity-friendly landscape management will always simultaneously promote multiple ES in agricultural landscapes. Future studies need to verify this pattern by using multi-year data, larger sets of ES and BD components and a study design that is appropriate to address larger spatial scales and relationships in several regions.
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  • Resultat 1-10 av 18
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