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- Jin, S. C., et al.
(author)
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Mutations disrupting neuritogenesis genes confer risk for cerebral palsy
- 2020
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 52:10, s. 1046-
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Journal article (peer-reviewed)abstract
- Whole-exome sequencing of 250 parent-offspring trios identifies an enrichment of rare damaging de novo mutations in individuals with cerebral palsy and implicates genetically mediated dysregulation of early neuronal connectivity in the etiology of this disorder. In addition to commonly associated environmental factors, genomic factors may cause cerebral palsy. We performed whole-exome sequencing of 250 parent-offspring trios, and observed enrichment of damaging de novo mutations in cerebral palsy cases. Eight genes had multiple damaging de novo mutations; of these, two (TUBA1AandCTNNB1) met genome-wide significance. We identified two novel monogenic etiologies,FBXO31andRHOB, and showed that theRHOBmutation enhances active-state Rho effector binding while theFBXO31mutation diminishes cyclin D levels. Candidate cerebral palsy risk genes overlapped with neurodevelopmental disorder genes. Network analyses identified enrichment of Rho GTPase, extracellular matrix, focal adhesion and cytoskeleton pathways. Cerebral palsy risk genes in enriched pathways were shown to regulate neuromotor function in aDrosophilareverse genetics screen. We estimate that 14% of cases could be attributed to an excess of damaging de novo or recessive variants. These findings provide evidence for genetically mediated dysregulation of early neuronal connectivity in cerebral palsy.
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| 2. |
- Shen, M., et al.
(author)
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Evaporative cooling over the Tibetan plateau induced by vegetation growth
- 2015
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In: Proceedings of the National Academy of Science of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 112:30, s. 9299-9304
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Journal article (peer-reviewed)abstract
- In the Arctic, climate warming enhances vegetation activity by extending the length of the growing season and intensifying maximum rates of productivity. In turn, increased vegetation productivity reduces albedo, which causes a positive feedback on temperature. Over the Tibetan Plateau (TP), regional vegetation greening has also been observed in response to recent warming. Here, we show that in contrast to arctic regions, increased growing season vegetation activity over the TP may have attenuated surface warming. This negative feedback on growing season vegetation temperature is attributed to enhanced evapotranspiration (ET). The extra energy available at the surface, which results from lower albedo, is efficiently dissipated by evaporative cooling. The net effect is a decrease in daily maximum temperature and the diurnal temperature range, which is supported by statistical analyses of in situ observations and by decomposition of the surface energy budget. A daytime cooling effect from increased vegetation activity is also modeled from a set of regional weather research and forecasting (WRF) mesoscale model simulations, but with a magnitude smaller than observed, likely because the WRF model simulates a weaker ET enhancement. Our results suggest that actions to restore native grasslands in degraded areas, roughly one-third of the plateau, will both facilitate a sustainable ecological development in this region and have local climate cobenefits. More accurate simulations of the biophysical coupling between the land surface and the atmosphere are needed to help understand regional climate change over the TP, and possible larger scale feedbacks between climate in the TP and the Asian monsoon system.
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