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Sökning: WFRF:(Lindblad C.) > (2015-2019)

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1.
  • Ostrander, E. A., et al. (författare)
  • Dog10K : An international sequencing effort to advance studies of canine domestication, phenotypes and health
  • 2019
  • Ingår i: National Science Review. - : Oxford University Press (OUP). - 2095-5138 .- 2053-714X. ; 6:4, s. 810-824
  • Tidskriftsartikel (refereegranskat)abstract
    • Dogs are the most phenotypically diverse mammalian species, and they possess more known heritable disorders than any other non-human mammal. Efforts to catalog and characterize genetic variation across well-chosen populations of canines are necessary to advance our understanding of their evolutionary history and genetic architecture. To date, no organized effort has been undertaken to sequence the world's canid populations. The Dog10K Consortium (http://www.dog10kgenomes.org) is an international collaboration of researchers from across the globe who will generate 20× whole genomes from 10 000 canids in 5 years. This effort will capture the genetic diversity that underlies the phenotypic and geographical variability of modern canids worldwide. Breeds, village dogs, niche populations and extended pedigrees are currently being sequenced, and de novo assemblies of multiple canids are being constructed. This unprecedented dataset will address the genetic underpinnings of domestication, breed formation, aging, behavior and morphological variation. More generally, this effort will advance our understanding of human and canine health. 
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2.
  • Casewell, Nicholas R, et al. (författare)
  • Solenodon genome reveals convergent evolution of venom in eulipotyphlan mammals.
  • 2019
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 116:51, s. 25745-25755
  • Tidskriftsartikel (refereegranskat)abstract
    • Venom systems are key adaptations that have evolved throughout the tree of life and typically facilitate predation or defense. Despite venoms being model systems for studying a variety of evolutionary and physiological processes, many taxonomic groups remain understudied, including venomous mammals. Within the order Eulipotyphla, multiple shrew species and solenodons have oral venom systems. Despite morphological variation of their delivery systems, it remains unclear whether venom represents the ancestral state in this group or is the result of multiple independent origins. We investigated the origin and evolution of venom in eulipotyphlans by characterizing the venom system of the endangered Hispaniolan solenodon (Solenodon paradoxus). We constructed a genome to underpin proteomic identifications of solenodon venom toxins, before undertaking evolutionary analyses of those constituents, and functional assessments of the secreted venom. Our findings show that solenodon venom consists of multiple paralogous kallikrein 1 (KLK1) serine proteases, which cause hypotensive effects in vivo, and seem likely to have evolved to facilitate vertebrate prey capture. Comparative analyses provide convincing evidence that the oral venom systems of solenodons and shrews have evolved convergently, with the 4 independent origins of venom in eulipotyphlans outnumbering all other venom origins in mammals. We find that KLK1s have been independently coopted into the venom of shrews and solenodons following their divergence during the late Cretaceous, suggesting that evolutionary constraints may be acting on these genes. Consequently, our findings represent a striking example of convergent molecular evolution and demonstrate that distinct structural backgrounds can yield equivalent functions.
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3.
  • Foote, Andrew D., et al. (författare)
  • Convergent evolution of the genomes of marine mammals
  • 2015
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 47:3, s. 272-275
  • Tidskriftsartikel (refereegranskat)abstract
    • Marine mammals from different mammalian orders share several phenotypic traits adapted to the aquatic environment and therefore represent a classic example of convergent evolution. To investigate convergent evolution at the genomic level, we sequenced and performed de novo assembly of the genomes of three species of marine mammals (the killer whale, walrus and manatee) from three mammalian orders that share independently evolved phenotypic adaptations to a marine existence. Our comparative genomic analyses found that convergent amino acid substitutions were widespread throughout the genome and that a subset of these substitutions were in genes evolving under positive selection and putatively associated with a marine phenotype. However, we found higher levels of convergent amino acid substitutions in a control set of terrestrial sister taxa to the marine mammals. Our results suggest that, whereas convergent molecular evolution is relatively common, adaptive molecular convergence linked to phenotypic convergence is comparatively rare.
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  • Lindblad, Peter, et al. (författare)
  • CyanoFactory, a European consortium to develop technologies needed to advance cyanobacteria as chassis for production of chemicals and fuels
  • 2019
  • Ingår i: Algal Research. - : Elsevier. - 2211-9264. ; 41
  • Forskningsöversikt (refereegranskat)abstract
    • CyanoFactory, Design, construction and demonstration of solar biofuel production using novel (photo) synthetic cell factories, was an R&D project developed in response to the European Commission FP7-ENERGY-2012-1 call "Future Emerging Technologies" and the need for significant advances in both new science and technologies to convert solar energy into a fuel. CyanoFactory was an example of "purpose driven" research and development with identified scientific goals and creation of new technologies. The present overview highlights significant outcomes of the project, three years after its successful completion. The scientific progress of CyanoFactory involved: (i) development of a ToolBox for cyanobacterial synthetic biology; (ii) construction of DataWarehouse/Bioinformatics web-based capacities and functions; (iii) improvement of chassis growth, functionality and robustness; (iv) introduction of custom designed genetic constructs into cyanobacteria, (v) improvement of photosynthetic efficiency towards hydrogen production; (vi) biosafety mechanisms; (vii) analyses of the designed cyanobacterial cells to identify bottlenecks with suggestions on further improvements; (viii) metabolic modelling of engineered cells; (ix) development of an efficient laboratory scale photobioreactor unit; and (x) the assembly and experimental performance assessment of a larger (1350 L) outdoor flat panel photobioreactor system during two seasons. CyanoFactory - Custom design and purpose construction of microbial cells for the production of desired products using synthetic biology - aimed to go beyond conventional paths to pursue innovative and high impact goals. CyanoFactory brought together ten leading European partners (universities, research organizations and enterprises) with a common goal - to develop the future technologies in Synthetic biology and Advanced photobioreactors.
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8.
  • Sakthikumar, Sharadha, et al. (författare)
  • SETD2 Is Recurrently Mutated in Whole-Exome Sequenced Canine Osteosarcoma
  • 2018
  • Ingår i: Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 0008-5472 .- 1538-7445. ; 78:13, s. 3421-3431
  • Tidskriftsartikel (refereegranskat)abstract
    • Osteosarcoma is a debilitating bone cancer that affects humans, especially children and adolescents. A homologous form of osteosarcoma spontaneously occurs in dogs, and its differential incidence observed across breeds allows for the investigation of tumor mutations in the context of multiple genetic backgrounds. Using whole-exome sequencing and dogs from three susceptible breeds (22 golden retrievers, 21 Rottweilers, and 23 greyhounds), we found that osteosarcoma tumors show a high frequency of somatic copy-number alterations (SCNA), affecting key oncogenes and tumor-suppressor genes. The across-breed results are similar to what has been observed for human osteosarcoma, but the disease frequency and somatic mutation counts vary in the three breeds. For all breeds, three mutational signatures (one of which has not been previously reported) and 11 significantly mutated genes were identified. TP53 was the most frequently altered gene (83% of dogs have either mutations or SCNA in TP53), recapitulating observations in human osteosarcoma. The second most frequently mutated gene, histone methyltransferase SETD2, has known roles in multiple cancers, but has not previously been strongly implicated in osteosarcoma. This study points to the likely importance of histone modifications in osteosarcoma and highlights the strong genetic similarities between human and dog osteosarcoma, suggesting that canine osteosarcoma may serve as an excellent model for developing treatment strategies in both species. Significance: Canine osteosarcoma genomics identify SETD2 as a possible oncogenic driver of osteosarcoma, and findings establish the canine model as a useful comparative model for the corresponding human disease.
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9.
  • Bari, Sadia, et al. (författare)
  • Soft X-ray Spectroscopy as a Probe for Gas-Phase Protein Structure : Electron Impact Ionization from Within
  • 2018
  • Ingår i: Chemistry - A European Journal. - : Wiley. - 0947-6539. ; 24:30, s. 7631-7636
  • Tidskriftsartikel (refereegranskat)abstract
    • Preservation of protein conformation upon transfer into the gas phase is key for structure determination of free single molecules, for example using X-ray free-electron lasers. In the gas phase, the helicity of melittin decreases strongly as the protein's protonation state increases. We demonstrate the sensitivity of soft X-ray spectroscopy to the gas-phase structure of melittin cations ([melittin+qH]q+, q=2-4) in a cryogenic linear radiofrequency ion trap. With increasing helicity, we observe a decrease of the dominating carbon 1s-π* transition in the amide C=O bonds for non-dissociative single ionization and an increase for non-dissociative double ionization. As the underlying mechanism we identify inelastic electron scattering. Using an independent atom model, we show that the more compact nature of the helical protein conformation substantially increases the probability for off-site intramolecular ionization by inelastic Auger electron scattering.
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