| 1. |
- 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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| 2. |
- Milillo, A., et al.
(författare)
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Investigating Mercury's Environment with the Two-Spacecraft BepiColombo Mission
- 2020
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Ingår i: Space Science Reviews. - : Springer Science and Business Media LLC. - 0038-6308 .- 1572-9672. ; 216:5
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Forskningsöversikt (refereegranskat)abstract
- The ESA-JAXA BepiColombo mission will provide simultaneous measurements from two spacecraft, offering an unprecedented opportunity to investigate magnetospheric and exospheric dynamics at Mercury as well as their interactions with the solar wind, radiation, and interplanetary dust. Many scientific instruments onboard the two spacecraft will be completely, or partially devoted to study the near-space environment of Mercury as well as the complex processes that govern it. Many issues remain unsolved even after the MESSENGER mission that ended in 2015. The specific orbits of the two spacecraft, MPO and Mio, and the comprehensive scientific payload allow a wider range of scientific questions to be addressed than those that could be achieved by the individual instruments acting alone, or by previous missions. These joint observations are of key importance because many phenomena in Mercury's environment are highly temporally and spatially variable. Examples of possible coordinated observations are described in this article, analysing the required geometrical conditions, pointing, resolutions and operation timing of different BepiColombo instruments sensors.
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| 3. |
- Tavakol, M, et al.
(författare)
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Diagnostic Approach to the Patients with Suspected Primary Immunodeficiency
- 2020
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Ingår i: Endocrine, metabolic & immune disorders drug targets. - : Bentham Science Publishers Ltd.. - 2212-3873 .- 1871-5303. ; 20:2, s. 157-171
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Tidskriftsartikel (refereegranskat)abstract
- Primary immunodeficiency diseases (PIDs) are a group of more than 350 disorders affecting distinct components of the innate and adaptive immune systems. In this review, the classic and advanced stepwise approach towards the diagnosis of PIDs are simplified and explained in detail.Results:Susceptibility to recurrent infections is the main hallmark of almost all PIDs. However, noninfectious complications attributable to immune dysregulation presenting with lymphoproliferative and/or autoimmune disorders are not uncommon. Moreover, PIDs could be associated with misleading presentations including allergic manifestations, enteropathies, and malignancies.Conclusion:Timely diagnosis is the most essential element in improving outcome and reducing the morbidity and mortality in PIDs. This wouldn’t be possible unless the physicians keep the diagnosis of PID in mind and be sufficiently aware of the approach to these patients.
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