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- Baek, Sungmin, et al.
(författare)
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The Alternative Splicing Regulator Nova2 Constrains Vascular Erk Signaling to Limit Specification of the Lymphatic Lineage
- 2019
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Ingår i: Developmental Cell. - : CELL PRESS. - 1534-5807 .- 1878-1551. ; 49:2, s. 279-292
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Tidskriftsartikel (refereegranskat)abstract
- The correct assignment of cell fate within fields of multipotent progenitors is essential for accurate tissue diversification. The first lymphatic vessels arise from pre-existing veins after venous endothelial cells become specified as lymphatic progenitors. Prox1 specifies lymphatic fate and labels these progenitors; however, the mechanisms restricting Prox1 expression and limiting the progenitor pool remain unknown. We identified a zebrafish mutant that displayed premature, expanded, and prolonged lymphatic specification. The gene responsible encodes the regulator of alternative splicing, Nova2. In zebrafish and human endothelial cells, Nova2 selectively regulates pre-mRNA splicing for components of signaling pathways and phosphoproteins. Nova2-deficient endothelial cells display increased Mapk/Erk signaling, and Prox1 expression is dynamically controlled by Erk signaling. We identify a mechanism whereby Nova2-regulated splicing constrains Erk signaling, thus limiting lymphatic progenitor cell specification. This identifies the capacity of a factor that tunes mRNA splicing to control assignment of cell fate during vascular differentiation.
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| 2. |
- Li, Wantong, et al.
(författare)
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Contrasting Drought Propagation Into the Terrestrial Water Cycle Between Dry and Wet Regions
- 2023
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Ingår i: Earth's Future. - 2328-4277. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- Drought's intensity and duration have increased in many regions over the last decades. However, the propagation of drought-induced water deficits through the terrestrial water cycle is not fully understood at a global scale. Here we study responses of monthly evaporation (ET) and runoff to soil moisture droughts occurring between 2001 and 2015 using independent gridded datasets based on machine learning-assisted upscaling of satellite and in-situ observations. We find that runoff and ET show generally contrasting drought responses across climate regimes. In wet regions, runoff is strongly reduced while ET is decoupled from soil moisture decreases and enhanced by sunny and warm weather typically accompanying soil moisture droughts. In drier regions, ET is reduced during droughts due to vegetation water stress, while runoff is largely unchanged as precipitation deficits are typically low in these regions and ET decreases are buffering runoff reductions. While these water flux drought responses are controlled by the large-scale climate regimes, they are additionally modulated by local vegetation characteristics. Land surface models capture the observed water cycle responses to drought in the case of runoff, but not for ET where the ET deficit (surplus) is overestimated (underestimated), related to a misrepresentation of the general soil moisture-evaporation interplay. In summary, our study illustrates how the joint analysis of machine learning-enhanced Earth observations can advance the understanding of global eco-hydrological processes, as well as the validation of land surface models.
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| 3. |
- Verberk, Inge M.W., et al.
(författare)
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Characterization of pre-analytical sample handling effects on a panel of Alzheimer's disease–related blood-based biomarkers : Results from the Standardization of Alzheimer's Blood Biomarkers (SABB) working group
- 2022
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Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 18:8, s. 1484-1497
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Pre-analytical sample handling might affect the results of Alzheimer's disease blood-based biomarkers. We empirically tested variations of common blood collection and handling procedures. Methods: We created sample sets that address the effect of blood collection tube type, and of ethylene diamine tetraacetic acid plasma delayed centrifugation, centrifugation temperature, aliquot volume, delayed storage, and freeze–thawing. We measured amyloid beta (Aβ)42 and 40 peptides with six assays, and Aβ oligomerization-tendency (OAβ), amyloid precursor protein (APP)699-711, glial fibrillary acidic protein (GFAP), neurofilament light (NfL), total tau (t-tau), and phosphorylated tau181. Results: Collection tube type resulted in different values of all assessed markers. Delayed plasma centrifugation and storage affected Aβ and t-tau; t-tau was additionally affected by centrifugation temperature. The other markers were resistant to handling variations. Discussion: We constructed a standardized operating procedure for plasma handling, to facilitate introduction of blood-based biomarkers into the research and clinical settings.
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