| 1. |
- Bryois, J., et al.
(författare)
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Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson’s disease
- 2020
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 52:5, s. 482-493
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have discovered hundreds of loci associated with complex brain disorders, but it remains unclear in which cell types these loci are active. Here we integrate genome-wide association study results with single-cell transcriptomic data from the entire mouse nervous system to systematically identify cell types underlying brain complex traits. We show that psychiatric disorders are predominantly associated with projecting excitatory and inhibitory neurons. Neurological diseases were associated with different cell types, which is consistent with other lines of evidence. Notably, Parkinson’s disease was genetically associated not only with cholinergic and monoaminergic neurons (which include dopaminergic neurons) but also with enteric neurons and oligodendrocytes. Using post-mortem brain transcriptomic data, we confirmed alterations in these cells, even at the earliest stages of disease progression. Our study provides an important framework for understanding the cellular basis of complex brain maladies, and reveals an unexpected role of oligodendrocytes in Parkinson’s disease. © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
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| 4. |
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| 5. |
- Andersson, L-O, et al.
(författare)
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A new neutron beam facility
- 2004
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Ingår i: Proc. of the 9th European Particle Accelerator Conference.
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Konferensbidrag (refereegranskat)
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| 6. |
- Sikora, M., et al.
(författare)
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The population history of northeastern Siberia since the Pleistocene
- 2019
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 570:7760
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Tidskriftsartikel (refereegranskat)abstract
- Northeastern Siberia has been inhabited by humans for more than 40,000 years but its deep population history remains poorly understood. Here we investigate the late Pleistocene population history of northeastern Siberia through analyses of 34 newly recovered ancient genomes that date to between 31,000 and 600 years ago. We document complex population dynamics during this period, including at least three major migration events: an initial peopling by a previously unknown Palaeolithic population of 'Ancient North Siberians' who are distantly related to early West Eurasian hunter-gatherers; the arrival of East Asian-related peoples, which gave rise to 'Ancient Palaeo-Siberians' who are closely related to contemporary communities from far-northeastern Siberia (such as the Koryaks), as well as Native Americans; and a Holocene migration of other East Asian-related peoples, who we name 'Neo-Siberians', and from whom many contemporary Siberians are descended. Each of these population expansions largely replaced the earlier inhabitants, and ultimately generated the mosaic genetic make-up of contemporary peoples who inhabit a vast area across northern Eurasia and the Americas.
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| 7. |
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| 8. |
- Hautakangas, H, et al.
(författare)
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Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles
- 2022
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:2, s. 152-
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Tidskriftsartikel (refereegranskat)abstract
- Migraine affects over a billion individuals worldwide but its genetic underpinning remains largely unknown. Here, we performed a genome-wide association study of 102,084 migraine cases and 771,257 controls and identified 123 loci, of which 86 are previously unknown. These loci provide an opportunity to evaluate shared and distinct genetic components in the two main migraine subtypes: migraine with aura and migraine without aura. Stratification of the risk loci using 29,679 cases with subtype information indicated three risk variants that seem specific for migraine with aura (in HMOX2, CACNA1A and MPPED2), two that seem specific for migraine without aura (near SPINK2 and near FECH) and nine that increase susceptibility for migraine regardless of subtype. The new risk loci include genes encoding recent migraine-specific drug targets, namely calcitonin gene-related peptide (CALCA/CALCB) and serotonin 1F receptor (HTR1F). Overall, genomic annotations among migraine-associated variants were enriched in both vascular and central nervous system tissue/cell types, supporting unequivocally that neurovascular mechanisms underlie migraine pathophysiology.
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| 9. |
- Laine, Christine M., et al.
(författare)
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WNT1 Mutations in Early-Onset Osteoporosis and Osteogenesis Imperfecta
- 2013
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 368:19, s. 1809-1816
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Tidskriftsartikel (refereegranskat)abstract
- This report identifies human skeletal diseases associated with mutations in WNT1. In 10 family members with dominantly inherited, early-onset osteoporosis, we identified a heterozygous missense mutation in WNT1, c.652T -> G (p.Cys218Gly). In a separate family with 2 siblings affected by recessive osteogenesis imperfecta, we identified a homozygous nonsense mutation, c.884C -> A, p.Ser295(star). In vitro, aberrant forms of the WNT1 protein showed impaired capacity to induce canonical WNT signaling, their target genes, and mineralization. In mice, Wnt1 was clearly expressed in bone marrow, especially in B-cell lineage and hematopoietic progenitors; lineage tracing identified the expression of the gene in a subset of osteocytes, suggesting the presence of altered cross-talk in WNT signaling between the hematopoietic and osteoblastic lineage cells in these diseases.
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| 10. |
- Moran, Meghan M., et al.
(författare)
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The risk of revision following total hip arthroplasty in patients with inflammatory bowel disease, a registry based study
- 2021
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:11
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Tidskriftsartikel (refereegranskat)abstract
- Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the intestinal tract and is associated with decreased bone mineral density. IBD patients are at higher risk of osteopenia, osteoporosis and fracture compared to non-IBD patients. The impact of IBD on the performance of orthopedic implants has not been well studied. We hypothesized that a history of IBD at the time of primary total hip arthroplasty (THA) would increase the risk of subsequent failure as assessed by revision surgery. A retrospective implant survival analysis was completed using the Swedish Hip Arthroplasty Registry and the Sweden National Patient Register. A total of 150,073 patients undergoing THA for osteoarthritis within an 18-year period were included in the study. THA patients with (n = 2,604) and without (n = 147,469) a history of IBD at the time of THA were compared with primary revision as the main endpoint and adjusted using sex, age category and comorbidity (Elixhauser scores) as covariates. We found that patients with a history of IBD had a relatively higher risk of revision surgery for septic causes while the non-IBD patients had a relatively higher risk of revision for aseptic causes (p = 0.004). Our findings suggest there may be an association between gut health and THA performance.
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| 11. |
- Pomp, Stephan, et al.
(författare)
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The New Uppsala Neutron Beam Facility
- 2004
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Ingår i: Proc. Int. Conf. on Nuclear Data for Science and Technology.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 12. |
- Prokofiev, A, et al.
(författare)
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A New Neutron Facility for Single-Event Effect Testing
- 2004
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Ingår i: Proceedings of the 6th International Workshop on Radiation Effects on Semiconductor Devices for Space Application. ; , s. 160-162
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 14. |
- Prokofiev, A. V, et al.
(författare)
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A new neutron beam facility at TSL
- 2006
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Ingår i: International workshop on Fast Neutron Detectors and Applications,Cape Town, South Africa, April 3-6. ; , s. 016-
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Konferensbidrag (refereegranskat)
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| 15. |
- Prokofiev, A.V, et al.
(författare)
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A new neutron facility for SEE testing
- 2005
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Ingår i: 8th European Conference on Radiation and its Effects on Components and systems, 2005, (in press).
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Konferensbidrag (refereegranskat)
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| 16. |
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| 17. |
- Prokofiev, A.V, et al.
(författare)
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A new neutron facility for single-event testing
- 2005
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Ingår i: IEEE International Reliability Physics Symposium (IRPS2005): San José, California, USA, April 17-21, 2005, (in press).
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Konferensbidrag (populärvet., debatt m.m.)
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| 18. |
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| 19. |
- Ahlqvist, E., et al.
(författare)
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Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables
- 2018
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Ingår i: Lancet Diabetes & Endocrinology. - : Elsevier BV. - 2213-8587. ; 6:5, s. 361-369
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Tidskriftsartikel (refereegranskat)abstract
- Background Diabetes is presently classified into two main forms, type 1 and type 2 diabetes, but type 2 diabetes in particular is highly heterogeneous. A refined classification could provide a powerful tool to individualise treatment regimens and identify individuals with increased risk of complications at diagnosis. Methods We did data-driven cluster analysis (k-means and hierarchical clustering) in patients with newly diagnosed diabetes (n=8980) from the Swedish All New Diabetics in Scania cohort. Clusters were based on six variables (glutamate decarboxylase antibodies, age at diagnosis, BMI, HbA(1c), and homoeostatic model assessment 2 estimates of beta-cell function and insulin resistance), and were related to prospective data from patient records on development of complications and prescription of medication. Replication was done in three independent cohorts: the Scania Diabetes Registry (n=1466), All New Diabetics in Uppsala (n=844), and Diabetes Registry Vaasa (n=3485). Cox regression and logistic regression were used to compare time to medication, time to reaching the treatment goal, and risk of diabetic complications and genetic associations. Findings We identified five replicable clusters of patients with diabetes, which had significantly different patient characteristics and risk of diabetic complications. In particular, individuals in cluster 3 (most resistant to insulin) had significantly higher risk of diabetic kidney disease than individuals in clusters 4 and 5, but had been prescribed similar diabetes treatment. Cluster 2 (insulin deficient) had the highest risk of retinopathy. In support of the clustering, genetic associations in the clusters differed from those seen in traditional type 2 diabetes. Interpretation We stratified patients into five subgroups with differing disease progression and risk of diabetic complications. This new substratification might eventually help to tailor and target early treatment to patients who would benefit most, thereby representing a first step towards precision medicine in diabetes.
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| 20. |
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| 21. |
- Djos, Anna, 1983, et al.
(författare)
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Multifocal Neuroblastoma and Central Hypoventilation in An Infant with Germline ALK F1174I Mutation
- 2022
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Ingår i: Diagnostics. - : MDPI AG. - 2075-4418. ; 12:9
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Tidskriftsartikel (refereegranskat)abstract
- A preterm infant with central hypoventilation was diagnosed with multifocal neuroblastoma. Congenital anomalies of the autonomic nervous system in association with neuroblastoma are commonly associated with germline mutations in PHOX2B. Further, the ALK gene is frequently mutated in both familial and sporadic neuroblastoma. Sanger sequencing of ALK and PHOX2B, SNP microarray of three tumor samples and whole genome sequencing of tumor and blood were performed. Genetic testing revealed a germline ALK F11741 mutation that was present in all tumor samples as well as in normal tissue samples from the patient. Neither of the patient's parents presented the ALK variant. Array profiling of the three tumor samples showed that two of them had only numerical aberrations, whereas one sample displayed segmental alterations, including a gain at chromosome 2p, resulting in two copies of the ALK-mutated allele. Whole genome sequencing confirmed the presence of the ALK variant and did not detect any aberrations in the coding or promotor region of PHOX2B. This study is to our knowledge the first to report a de novo ALK F11741 germline mutation. This may not only predispose to congenital multifocal neuroblastoma but may also contribute to the respiratory dysfunction seen in this patient.
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| 22. |
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| 23. |
- Hosseini, Vahid, 1987-, et al.
(författare)
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Correction to : Time-temperature-precipitation and property diagrams for super duplex stainless steel weld metals (Welding in the World, (2018), 62, 3, (517-533), 10.1007/s40194-018-0548-z)
- 2018
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Ingår i: Welding in the World. - : Springer Science and Business Media LLC. - 0043-2288 .- 1878-6669. ; 62:4, s. 893-
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Tidskriftsartikel (refereegranskat)abstract
- Unfortunately due to typesetting mistakes, Tables 4-€“6 have been displayed erroneously in the article. © 2018, International Institute of Welding.
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| 24. |
- Kantre, Karim-Alexandros, et al.
(författare)
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SIGMA : A Set-up for In-situ Growth, Material modification and Analysis by ion beams
- 2020
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Ingår i: Nuclear Instruments and Methods in Physics Research Section B. - : ELSEVIER. - 0168-583X .- 1872-9584. ; 463, s. 96-100
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Tidskriftsartikel (refereegranskat)abstract
- We present a set-up for in-situ non-destructive high-resolution composition depth profiling by ion beams developed at the 5 MV 15 SDH-2 Tandem accelerator at the Angstrom laboratory at Uppsala University. The scattering chamber allows thin film deposition, modification and characterization which can be used to study the very initial stages of near-surface processes such as thin film growth, oxidation, annealing or ion implantation. We describe the available instrumentation with its specifications in detail and present experimental applications, i.e. the characterization of reactive in-situ thin film growth and controlled oxidation, as well as a study of ion implantation and the impact of thermal annealing and surface oxidation on the implantation profiles.
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