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- Helbig, K. L., et al.
(författare)
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De Novo Pathogenic Variants in CACNA1E Cause Developmental and Epileptic Encephalopathy with Contractures, Macrocephaly, and Dyskinesias
- 2018
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 103:5, s. 666-678
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Tidskriftsartikel (refereegranskat)abstract
- Developmental and epileptic encephalopathies (DEEs) are severe neurodevelopmental disorders often beginning in infancy or early childhood that are characterized by intractable seizures, abundant epileptiform activity on EEG, and developmental impairment or regression. CACNA1E is highly expressed in the central nervous system and encodes the alpha(1)-subunit of the voltage-gated Ca(V)2.3 channel, which conducts high voltage-activated R-type calcium currents that initiate synaptic transmission. Using next-generation sequencing techniques, we identified de novo CACNA1E variants in 30 individuals with DEE, characterized by refractory infantile-onset seizures, severe hypotonia, and profound developmental impairment, often with congenital contractures, macrocephaly, hyperkinetic movement disorders, and early death. Most of the 14, partially recurring, variants cluster within the cytoplasmic ends of all four S6 segments, which form the presumed Ca(V)2.3 channel activation gate. Functional analysis of several S6 variants revealed consistent gain-of-function effects comprising facilitated voltage-dependent activation and slowed inactivation. Another variant located in the domain II S4-S5 linker results in facilitated activation and increased current density. Five participants achieved seizure freedom on the anti-epileptic drug topiramate, which blocks R-type calcium channels. We establish pathogenic variants in CACNA1E as a cause of DEEs and suggest facilitated R-type calcium currents as a disease mechanism for human epilepsy and developmental disorders.
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- Nicolás, César, et al.
(författare)
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Chemical changes in organic matter after fungal colonization in a nitrogen fertilized and unfertilized Norway spruce forest
- 2017
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Ingår i: Plant and Soil. - : Springer Science and Business Media LLC. - 0032-079X .- 1573-5036. ; 419:1-2, s. 113-126
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Decomposition and transformation of organic matter (OM) in forest soils are conducted by the concomitant action of saprotrophic and mycorrhizal fungi. Here, we examine chemical changes in OM after fungal colonization in nitrogen fertilized and unfertilized soils from a Norway spruce forest. Methods: Sand-filled bags amended with composted maize leaves were placed in the forest soil and harvested after 17 months. Infrared and near edge X-ray absorption fine structure spectroscopies were used to study the chemical changes in the OM. Fungal community composition of the bags was also evaluated. Results: The proportion of ectomycorrhizal fungi declined in the fertilized plots, but the overall fungal community composition was similar between N treatments. Decomposition of the OM was, independently of the N level or soil horizon, accompanied by an increase of C/N ratio of the mesh-bag content. Moreover, the proportions of carboxylic compounds in the incubated OM increased in the mineral horizon, while heterocyclic-N compounds decreased, especially in unfertilized plots with higher N demand from the trees. Conclusions: Our results indicate that more oxidized organic C and less heterocyclic-N proportions in the OM remain after fungal colonization in the mineral layers, and suggest that ectomycorrhizal fungi transfer less heterocyclic-N from the mesh bags to the host trees under high N levels.
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- Schwellnus, Martin, et al.
(författare)
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How much is too much? (Part 2) International Olympic Committee consensus statement on load in sport and risk of illness
- 2016
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Ingår i: British Journal of Sports Medicine. - : BMJ PUBLISHING GROUP. - 0306-3674 .- 1473-0480. ; 50:17, s. 1043-1052
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Tidskriftsartikel (refereegranskat)abstract
- The modern-day athlete participating in elite sports is exposed to high training loads and increasingly saturated competition calendar. Emerging evidence indicates that inappropriate load management is a significant risk factor for acute illness and the overtraining syndrome. The IOC convened an expert group to review the scientific evidence for the relationship of loadincluding rapid changes in training and competition load, competition calendar congestion, psychological load and traveland health outcomes in sport. This paper summarises the results linking load to risk of illness and overtraining in athletes, and provides athletes, coaches and support staff with practical guidelines for appropriate load management to reduce the risk of illness and overtraining in sport. These include guidelines for prescription of training and competition load, as well as for monitoring of training, competition and psychological load, athlete well-being and illness. In the process, urgent research priorities were identified.
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