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- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 3. |
- Gurnell, Angela M., et al.
(författare)
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The geomorphological context and impact of the linear emergent macrophyte, Sparganium erectum L. : a statistical analysis of observations from British rivers
- 2013
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Ingår i: Earth Surface Processes and Landforms. - : Wiley. - 0197-9337 .- 1096-9837. ; 38:15, s. 1869-1880
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Tidskriftsartikel (refereegranskat)abstract
- This paper explores the geomorphological context and impact of the widely-occurring, linear emergent macrophyte, Sparganium erectum. Forty-seven sites across Britain were selected for field investigation, spanning the range of environmental conditions within which Sparganium erectum had been found to be present in previous analyses of national data sets. A combination of descriptive graphs and statistics, principal components analysis, and Kruskal-Wallis tests were used to explore the large multivariate data set collected at the 47 sites. The analyses showed that Sparganium erectum is present in significant quantities in relatively narrow and shallow (< 18m wide and<0.9m deep to the limit of terrestrial vegetation), low gradient (maximum 0.004) channels of varying bed sediment calibre (cobble to silt). Within these environments, S. erectum stands (features) were associated with fine sediment retention, aggradation and submerged landform construction, leading to bench development and so, potentially, to adjustments in channel form and position. Sediment retention and landform construction within S. erectum features was most strongly apparent within reaches with a relatively high S. erectum cover and the presence of large area S. erectum features. It was also associated more weakly with S. erectum features that were comprised of relatively higher densities of plants with relatively smaller inter-plant spacing and fewer leaves. The sediment retained in S. erectum features and associated bench and bank toe deposits showed larger numbers and species of viable seeds, indicating the potential for colonization and growth of other species on S. erectum features once they aggrade above the low flow water level and are no longer a suitable habitat for S. erectum.
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- Buetti-Dinh, Antoine, et al.
(författare)
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Sensitivity Analysis of the NPM-ALK Signalling Network Reveals Important Pathways for Anaplastic Large Cell Lymphoma Combination Therapy
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:9
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Tidskriftsartikel (refereegranskat)abstract
- A large subset of anaplastic large cell lymphoma (ALCL) patients harbour a somatic aberration in which anaplastic lymphoma kinase (ALK) is fused to nucleophosmin (NPM) resulting in a constitutively active signalling fusion protein, NPM-ALK. We computationally simulated the signalling network which mediates pathological cell survival and proliferation through NPM-ALK to identify therapeutically targetable nodes through which it may be possible to regain control of the tumourigenic process. The simulations reveal the predominant role of the VAV1-CDC42 (cell division control protein 42) pathway in NPM-ALK-driven cellular proliferation and of the Ras / mitogen-activated ERK kinase (MEK) / extracellular signal-regulated kinase (ERK) cascade in controlling cell survival. Our results also highlight the importance of a group of interleukins together with the Janus kinase 3 (JAK3) / signal transducer and activator of transcription 3 (STAT3) signalling in the development of NPM-ALK derived ALCL. Depending on the activity of JAK3 and STAT3, the system may also be sensitive to activation of protein tyrosine phosphatase-1 (SHP1), which has an inhibitory effect on cell survival and proliferation. The identification of signalling pathways active in tumourigenic processes is of fundamental importance for effective therapies. The prediction of alternative pathways that circumvent classical therapeutic targets opens the way to preventive approaches for countering the emergence of cancer resistance.
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- Zabriskie, Matthew S., et al.
(författare)
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BCR-ABL1 Compound Mutations Combining Key Kinase Domain Positions Confer Clinical Resistance to Ponatinib in Ph Chromosome-Positive Leukemia
- 2014
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Ingår i: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 26:3, s. 428-442
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Tidskriftsartikel (refereegranskat)abstract
- Ponatinib is the only currently approved tyrosine kinase inhibitor (TKI) that suppresses all BCR-ABL1 single mutants in Philadelphia chromosome-positive (Ph+) leukemia, including the recalcitrant BCR-ABL1(T315I) mutant. However, emergence of compound mutations in a BCR-ABL1 allele may confer ponatinib resistance. We found that clinically reported BCR-ABL1 compound mutants center on 12 key positions and confer varying resistance to imatinib, nilotinib, dasatinib, ponatinib, rebastinib, and bosutinib. T315I-inclusive compound mutants confer high-level resistance to TKIs, including ponatinib. In vitro resistance profiling was predictive of treatment outcomes in Ph+ leukemia patients. Structural explanations for compound mutation-based resistance were obtained through molecular dynamics simulations. Our findings demonstrate that BCR-ABL1 compound mutants confer different levels of TKI resistance, necessitating rational treatment selection to optimize clinical outcome.
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