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- Juday, G.P, et al.
(author)
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Chapter 14: Forests, Land Management and Agriculture
- 2005
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In: The Arctic Climate Impact Assessment - The Scientific Report. - Cambridge : Cambridge University Press. - 0521865093 ; , s. 781-862
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Book chapter (other academic/artistic)
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| 3. |
- Saliba-Gustafsson, P., et al.
(author)
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Subclinical atherosclerosis and its progression are modulated by PLIN2 through a feed-forward loop between LXR and autophagy
- 2019
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In: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 286:6, s. 660-675
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Journal article (peer-reviewed)abstract
- Background Hyperlipidaemia is a major risk factor for cardiovascular disease, and atherosclerosis is the underlying cause of both myocardial infarction and stroke. We have previously shown that the Pro251 variant of perilipin-2 reduces plasma triglycerides and may therefore be beneficial to reduce atherosclerosis development. Objective We sought to delineate putative beneficial effects of the Pro251 variant of perlipin-2 on subclinical atherosclerosis and the mechanism by which it acts. Methods A pan-European cohort of high-risk individuals where carotid intima-media thickness has been assessed was adopted. Human primary monocyte-derived macrophages were prepared from whole blood from individuals recruited by perilipin-2 genotype or from buffy coats from the Karolinska University hospital blood central. Results The Pro251 variant of perilipin-2 is associated with decreased intima-media thickness at baseline and over 30 months of follow-up. Using human primary monocyte-derived macrophages from carriers of the beneficial Pro251 variant, we show that this variant increases autophagy activity, cholesterol efflux and a controlled inflammatory response. Through extensive mechanistic studies, we demonstrate that increase in autophagy activity is accompanied with an increase in liver-X-receptor (LXR) activity and that LXR and autophagy reciprocally activate each other in a feed-forward loop, regulated by CYP27A1 and 27OH-cholesterol. Conclusions For the first time, we show that perilipin-2 affects susceptibility to human atherosclerosis through activation of autophagy and stimulation of cholesterol efflux. We demonstrate that perilipin-2 modulates levels of the LXR ligand 27OH-cholesterol and initiates a feed-forward loop where LXR and autophagy reciprocally activate each other; the mechanism by which perilipin-2 exerts its beneficial effects on subclinical atherosclerosis.
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- Bonomi, A, et al.
(author)
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Analysis of the genetic variants associated with circulating levels of sgp130. Results from the IMPROVE study
- 2020
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In: Genes and immunity. - : Springer Science and Business Media LLC. - 1476-5470 .- 1466-4879. ; 21:2, s. 100-108
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Journal article (peer-reviewed)abstract
- The genes regulating circulating levels of soluble gp130 (sgp130), the antagonist of the inflammatory response in atherosclerosis driven by interleukin 6, are largely unknown. Aims of the present study were to identify genetic loci associated with circulating sgp130 and to explore the potential association between variants associated with sgp130 and markers of subclinical atherosclerosis. The study is based on IMPROVE (n = 3703), a cardiovascular multicentre study designed to investigate the determinants of carotid intima media thickness, a measure of subclinical atherosclerosis. Genomic DNA was genotyped by the CardioMetaboChip and ImmunoChip. About 360,842 SNPs were tested for association with log-transformed sgp130, using linear regression adjusted for age, gender, and population stratification using PLINK v1.07. A p value of 1 × 10−5 was chosen as threshold for significance value. In an exploratory analysis, SNPs associated with sgp130 were tested for association with c-IMT measures. We identified two SNPs significantly associated with sgp130 levels and 24 showing suggestive association with sgp130 levels. One SNP (rs17688225) on chromosome 14 was positively associated with sgp130 serum levels (β = 0.03 SE = 0.007, p = 4.77 × 10−5) and inversely associated with c-IMT (c-IMTmean–maxβ = −0.001 SE = 0.005, p = 0.0342). Our data indicate that multiple loci regulate sgp130 levels and suggest a possible common pathway between sgp130 and c-IMT measures.
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- Langstrom, S, et al.
(author)
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Haematopoietic Stem Cell Transplantation in Children Shifts the Coagulation System towards a Pro-Coagulant State
- 2018
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In: Thrombosis and haemostasis. - : Georg Thieme Verlag KG. - 2567-689X .- 0340-6245. ; 118:8, s. 1390-1396
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Journal article (peer-reviewed)abstract
- Coagulation system is disturbed by several mechanisms after allogeneic haematopoietic stem cell transplantation (HSCT). We evaluated the effect of HSCT on coagulation system by various conventional and investigational methods in 30 children and adolescents who received HSCT due to haematological malignancies. Pro-thrombin fragment 1 + 2, a specific measure of thrombin generation, and von Willebrand factor, a measure of endothelial activation, increased after conditioning treatment, and remained elevated until 3 months after HSCT (p < 0.05 for all comparisons to pre-conditioning treatment). D-dimer, a measure of fibrin turnover, was elevated from the second week onwards until 4 weeks after HSCT (p < 0.05). Endogenous thrombin potential was increased after conditioning, and at 2 weeks after HSCT (p < 0.05). Furthermore, the activities of acute phase reactants fibrinogen and coagulation factor VIII were increased (p < 0.05 for all comparisons to pre-conditioning treatment) from the first week onwards up to 3 weeks and 3 months after HSCT, respectively. Taken together, paediatric patients receiving HSCT demonstrate distinct and prolonged variations in the coagulation system towards a pro-coagulant state. This shift is of importance when estimating the risk of haemostatic and thrombotic complications in these children.
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| 10. |
- Mateos, Marion K., et al.
(author)
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Genome-wide association meta-analysis of single-nucleotide polymorphisms and symptomatic venous thromboembolism during therapy for acute lymphoblastic leukemia and lymphoma in caucasian children
- 2020
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In: Cancers. - : MDPI AG. - 2072-6694. ; 12:5
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Journal article (peer-reviewed)abstract
- Symptomatic venous thromboembolism (VTE) occurs in five percent of children treated for acute lymphoblastic leukemia (ALL), but whether a genetic predisposition exists across different ALL treatment regimens has not been well studied. Methods: We undertook a genome-wide association study (GWAS) meta-analysis for VTE in consecutively treated children in the Nordic/Baltic acute lymphoblastic leukemia 2008 (ALL2008) cohort and the Australian Evaluation of Risk of ALL Treatment-Related Side-Effects (ERASE) cohort. A total of 92 cases and 1481 controls of European ancestry were included. Results: No SNPs reached genome-wide significance (p < 5 × 10−8) in either cohort. Among the top 34 single-nucleotide polymorphisms (SNPs) (p < 1 × 10−6), two loci had concordant effects in both cohorts: ALOX15B (rs1804772) (MAF: 1%; p = 3.95 × 10−7) that influences arachidonic acid metabolism and thus platelet aggregation, and KALRN (rs570684) (MAF: 1%; p = 4.34 × 10−7) that has been previously associated with risk of ischemic stroke, atherosclerosis, and early-onset coronary artery disease. Conclusion: This represents the largest GWAS meta-analysis conducted to date associating SNPs to VTE in children and adolescents treated on childhood ALL protocols. Validation of these findings is needed and may then lead to patient stratification for VTE preventive interventions. As VTE hemostasis involves multiple pathways, a more powerful GWAS is needed to detect combination of variants associated with VTE.
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