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| 2. |
- 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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| 3. |
- 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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| 4. |
- 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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| 5. |
- Hertzman, S., et al.
(författare)
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Nitrogen Solubility in Alloy Systems Relevant to Stainless Steels
- 2021
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Ingår i: Metallurgical and Materials Transactions. A. - : Springer Nature. - 1073-5623 .- 1543-1940. ; 52:9, s. 3811-3820
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Tidskriftsartikel (refereegranskat)abstract
- High-performance stainless steels are alloyed with nitrogen for several different reasons. For the austenitic grades, the kinetics of deleterious phase transformations are delayed, the strength is increased, and the corrosion resistance is improved. For duplex steels, the weldability and corrosion resistance depend directly on their nitrogen contents. Reliable databases are crucial for the development of new stainless steels and their processing. In order to calibrate the existing thermodynamic data, a series of experiments was undertaken. Several laboratory alloys in Fe–Cr–X systems, where X = Ni, Mn, Cu, were reacted with nitrogen gas at nitrogen activities 0.5 and 1 in the temperature range from 1050 °C to 1350 °C and subsequently analyzed for nitrogen solubility and phase constitution. A novel, simplified experimental technique was used, providing a dew point that is low enough to allow for fast nitrogen transport through the specimen surface, ensuring equilibrium conditions. The results are compared to thermodynamic equilibrium calculations.
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| 6. |
- Liu, Jianling, et al.
(författare)
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Effect of Cooling Rate after Solution Treatment on Subsequent Phase Separation Evolution in Super Duplex Stainless Steel 25Cr-7Ni (wt.%)
- 2022
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Ingår i: Metals. - : MDPI AG. - 2075-4701. ; 12:5, s. 890-
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Tidskriftsartikel (refereegranskat)abstract
- The effect of cooling rate after solution treatment on the initial structure of super duplex stainless steel 25Cr-7Ni (wt.%), and the effect of the initial structure on phase separation (PS) evolution during subsequent aging were investigated. The nanostructure in the bulk of the steel was studied using small-angle neutron scattering (SANS). Ex situ SANS experiments showed that the rate of PS differs during aging, due to the different initial structures imposed by the difference in cooling rate after solution treatment. In situ SANS experiments revealed that the PS is already pronounced after aging at 475 degrees C for 180 min and that a slower cooling rate after solution treatment will lead to more significant PS. Hence, PS depends on the plate thickness, imposing different cooling rates in the production of duplex stainless steels.
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| 7. |
- Liu, Jianling, et al.
(författare)
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Small-angle neutron scattering study on phase separation in a super duplex stainless steel at 300°C-Comparing hot-rolled and TIG welded material
- 2022
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Ingår i: Materials Characterization. - : Elsevier BV. - 1044-5803 .- 1873-4189. ; 190, s. 112044-
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Tidskriftsartikel (refereegranskat)abstract
- The evolution of nanoscale phase separation in the ferrite phase of super duplex stainless steel 25Cr 7Ni (wt%) (SDSS 2507) and two SDSS TIG (tungsten inert gas) weldments have been quantitatively investigated by small-angle neutron scattering (SANS). The results show that the phase separation is more pronounced in the SDSS weldments in comparison to the base metal SDSS 2507, especially after aging for 35,000 h at 300 °C. These results correlate with the higher ferrite micro-hardness in the aged TIG weldments than in the SDSS 2507. The enhanced phase separation is partly due to the higher contents of Cr and Ni in the ferrite of TIG weldments compared to SDSS 2507 base metal, revealed by energy-dispersive X-ray spectroscopy (EDS). Additionally, the residual strain measurements through focused ion beam and digital image correlation (FIB-DIC), indicate larger residual strains in the ferrite of weldments than in the base metal SDSS 2507. This is also believed to contribute to the enhanced phase separation.
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| 8. |
- Tripathy, Devjit, et al.
(författare)
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Importance of obtaining independent measures of insulin secretion and insulin sensitivity during the same test - Results with the Botnia clamp
- 2003
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Ingår i: Diabetes Care. - 1935-5548. ; 26:5, s. 1395-1401
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE - To validate and apply a method for independent assessment of insulin secretion and insulin sensitivity (S-l) during file same test that is, an intravenous glucose tolerance test followed by a euglycemic-hyperinsulinemic clamp, also called the Botnia clamp. This test was then applied to nondiabetic subjects with (FH+)and without (FH-) a first-degree family history of diabetes. RESEARCH DESIGN AND METHODS - The Botnia clamp measures the first-phase insulin response (FPIR) to 0.3g/k, glucose i.v. and insulin sensitivity (NI-value) front a 2-h euglycemic clamp begun 60 ruin alter the glucose bolus. The W-value obtained during the Botnia clamp was compared With M-values obtained during a regular euglycemic clamp without prior glucose bolus. Repeated tests were performed in random order in subjects with normal and abnormal glucose tolerance, Finally, the test was applied to subjects with and without a family history of type 2 diabetes. RESULTS - S-l and insulin secretion from this test showed a high degree of reproducibility, and the M-value obtained with the Botnia clamp correlated strongly,with the M-value from a euglycemic clamp without prior glucose bolus (r - 0.953, P < 0.005). FH+ subjects showed decreased S-l (P = 0.02), hut similar FPIR, compared with FH- subjects, However, insulin Secretion adjusted for file degree of insulin resistance was significantly impaired (P = 0.04). CONCLUSIONS - In conclusion, the Botnia clamp provides reliable and independent measures of S-l and beta-cell function during, the same test. As illustrated above, knowledge of the degree of S-l is mandatory When presenting data on insulin secretion.
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