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- Jin, S. C., et al.
(författare)
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Mutations disrupting neuritogenesis genes confer risk for cerebral palsy
- 2020
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 52:10
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Tidskriftsartikel (refereegranskat)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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- Chuvilin, E., et al.
(författare)
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In-situ temperatures and thermal properties of the East Siberian Arctic shelf sediments : Key input for understanding the dynamics of subsea permafrost
- 2022
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Ingår i: Marine and Petroleum Geology. - : Elsevier BV. - 0264-8172 .- 1873-4073. ; 138
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Tidskriftsartikel (refereegranskat)abstract
- Significant reserves of methane (CH4) are held in the Arctic shelf, but the release of CH4 to the overlying ocean and, subsequently, to the atmosphere has been believed to be restricted by impermeable subsea permafrost, which has sealed the upper sediment layers for thousands of years. Our studies demonstrate progressive degradation of subsea permafrost which controls the scales of CH4 release from the sediment into the water-atmospheric system. Thus, new knowledge about the thermal state of subsea permafrost is crucial for better understanding of the permafrost -hydrate system and associated CH4 release from the East Siberian Arctic Shelf (ESAS) – the broadest and shallowest shelf in the World Ocean, which contains about 80% of subsea permafrost and giant pools of hydrates. Meanwhile, the ESAS, still presents large knowledge gaps in many aspects, especially with respect to subsea permafrost distribution and physical properties of bottom sediments. New field data show that the ESAS has an unfrozen (ice-free) upper sediment layer, which in-situ temperature is −1.0 to −1.8 °C and 0.6оС above the freezing point. On one hand, these cold temperature patterns may be related to the presence of subsea permafrost, which currently primarily occurs in the part of the ESAS that is shallower than 100 m, while ice-bearing sediments may also exist locally under deeper water in the Laptev Sea. On the other hand, the negative bottom sediment temperatures of −1.8 °C measured on the Laptev Sea continental slope sediments underlying water columns as deep as down to 330 m may result from dissociation of gas hydrates or possibly from dense water cascading down from the shelf. In contrast, data collected on recent expeditions in the northern Laptev shelf, zones of warmer bottom temperatures are coinciding with methane seeps, likely induced by seismic and tectonic activity in the area. These warm temperatures are not seen in the East Siberian Sea area, not even in areas of methane seeps, yet with little seismic activity.The thermal conductivity and heat capacity of bottom sediments recorded in the database of thermal parameters for the ESAS areas mainly depend on their lithification degree (density or porosity), moisture content, and particle size distribution. The thermal conductivity and heat capacity average about 1.0 W/(m·K) and 2900 kJ/(m3·K), with ±20% and ±10% variance, respectively, in all sampled Arctic sediments to a sub-bottom interval of 0–0.5 m.
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