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- Strakova, A., et al.
(författare)
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Recurrent horizontal transfer identifies mitochondrial positive selection in a transmissible cancer
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Autonomous replication and segregation of mitochondrial DNA (mtDNA) creates the potential for evolutionary conflict driven by emergence of haplotypes under positive selection for 'selfish' traits, such as replicative advantage. However, few cases of this phenomenon arising within natural populations have been described. Here, we survey the frequency of mtDNA horizontal transfer within the canine transmissible venereal tumour (CTVT), a contagious cancer clone that occasionally acquires mtDNA from its hosts. Remarkably, one canine mtDNA haplotype, A1d1a, has repeatedly and recently colonised CTVT cells, recurrently replacing incumbent CTVT haplotypes. An A1d1a control region polymorphism predicted to influence transcription is fixed in the products of an A1d1a recombination event and occurs somatically on other CTVT mtDNA backgrounds. We present a model whereby 'selfish' positive selection acting on a regulatory variant drives repeated fixation of A1d1a within CTVT cells.
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- Bisson, Nicolas, et al.
(författare)
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The Adaptor Protein Grb2 Is Not Essential for the Establishment of the Glomerular Filtration Barrier
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:11, s. e50996-
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Tidskriftsartikel (refereegranskat)abstract
- The kidney filtration barrier is formed by the combination of endothelial cells, basement membrane and epithelial cells called podocytes. These specialized actin-rich cells form long and dynamic protrusions, the foot processes, which surround glomerular capillaries and are connected by specialized intercellular junctions, the slit diaphragms. Failure to maintain the filtration barrier leads to massive proteinuria and nephrosis. A number of proteins reside in the slit diaphragm, notably the transmembrane proteins Nephrin and Neph1, which are both able to act as tyrosine phosphorylated scaffolds that recruit cytoplasmic effectors to initiate downstream signaling. While association between tyrosine-phosphorylated Neph1 and the SH2/SH3 adaptor Grb2 was shown in vitro to be sufficient to induce actin polymerization, in vivo evidence supporting this finding is still lacking. To test this hypothesis, we generated two independent mouse lines bearing a podocyte-specific constitutive inactivation of the Grb2 locus. Surprisingly, we show that mice lacking Grb2 in podocytes display normal renal ultra-structure and function, thus demonstrating that Grb2 is not required for the establishment of the glomerular filtration barrier in vivo. Moreover, our data indicate that Grb2 is not required to restore podocyte function following kidney injury. Therefore, although in vitro experiments suggested that Grb2 is important for the regulation of actin dynamics, our data clearly shows that its function is not essential in podocytes in vivo, thus suggesting that Grb2 rather plays a secondary role in this process.
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- Naing, C. L., et al.
(författare)
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Single-vehicle collisions in Europe: analysis using real-world and crash-test data
- 2008
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Ingår i: International Journal of Crashworthiness. - : Informa UK Limited. - 1358-8265 .- 1754-2111. ; 13:2, s. 219-229
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Tidskriftsartikel (refereegranskat)abstract
- Many European road casualties result from vehicles leaving the road, often impacting roadside obstacles. As part of the European Commission-funded project RISER (Roadside Infrastructure for Safer European Roads), several activities were undertaken to collate the type of real world crash data which is needed to understand single vehicle crash situations and relate this to crash-test data mandated in the European Union. Accident data were collected and used to create databases exclusively for single-vehicle collisions on major rural roads, simulation software was used to further understand impacts with roadside structures, and an inventory of crash-test data was collected for impacts with poles and safety barriers. The combination of accident data, simulations and crash-test data has provided a unique insight into the characteristics of single-vehicle collisions, helping those involved in the design and evaluation of the roadside environment to understand them better and make recommendations for consideration when drafting design guidelines.
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- Rizzi, Arthur, et al.
(författare)
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Comparative study of two optimization frameworks applied to case III : Induced-drag minimization
- 2016
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Ingår i: 54th AIAA Aerospace Sciences Meeting. - : American Institute of Aeronautics and Astronautics. - 9781624103933
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Konferensbidrag (refereegranskat)abstract
- The paper describes the comparative study of two optimization frameworks on Case III, twist optimization for induced-drag minimization. Both frameworks use gradient-based optimizers. With different flow solvers and other algorithmic differences they find different optimized shapes, all with the CD,i reduced by around 1 count.
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