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| 2. |
- Juday, G.P, et al.
(författare)
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Chapter 14: Forests, Land Management and Agriculture
- 2005
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Ingår i: The Arctic Climate Impact Assessment - The Scientific Report. - Cambridge : Cambridge University Press. - 0521865093 ; , s. 781-862
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 3. |
- Saliba-Gustafsson, P., et al.
(författare)
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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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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 286:6, s. 660-675
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Tidskriftsartikel (refereegranskat)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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| 6. |
- Bonomi, A, et al.
(författare)
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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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Ingår i: Genes and immunity. - : Springer Science and Business Media LLC. - 1476-5470 .- 1466-4879. ; 21:2, s. 100-108
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Tidskriftsartikel (refereegranskat)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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| 9. |
- Langstrom, S, et al.
(författare)
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Haematopoietic Stem Cell Transplantation in Children Shifts the Coagulation System towards a Pro-Coagulant State
- 2018
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Ingår i: Thrombosis and haemostasis. - : Georg Thieme Verlag KG. - 2567-689X .- 0340-6245. ; 118:8, s. 1390-1396
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Tidskriftsartikel (refereegranskat)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.
(författare)
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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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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 12:5
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Tidskriftsartikel (refereegranskat)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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| 11. |
- Mooij, Wolf M., et al.
(författare)
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Modeling water quality in the Anthropocene : directions for the next-generation aquatic ecosystem models
- 2019
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Ingår i: Current Opinion in Environmental Sustainability. - : Elsevier BV. - 1877-3435 .- 1877-3443. ; 36, s. 85-95
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Forskningsöversikt (refereegranskat)abstract
- Everything changes and nothing stands still (Heraclitus). Here we review three major improvements to freshwater aquatic ecosystem models - and ecological models in general - as water quality scenario analysis tools towards a sustainable future. To tackle the rapid and deeply connected dynamics characteristic of the Anthropocene, we argue for the inclusion of eco-evolutionary, novel ecosystem and social-ecological dynamics. These dynamics arise from adaptive responses in organisms and ecosystems to global environmental change and act at different integration levels and different time scales. We provide reasons and means to incorporate each improvement into aquatic ecosystem models. Throughout this study we refer to Lake Victoria as a microcosm of the evolving novel social-ecological systems of the Anthropocene. The Lake Victoria case clearly shows how interlinked eco-evolutionary, novel ecosystem and social-ecological dynamics are, and demonstrates the need for transdisciplinary research approaches towards global sustainability.
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| 15. |
- Barker, Roger A., et al.
(författare)
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GDNF and Parkinson's Disease : Where Next? A Summary from a Recent Workshop
- 2020
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Ingår i: Journal of Parkinson's Disease. - 1877-7171. ; 10:3, s. 875-891
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Tidskriftsartikel (refereegranskat)abstract
- The concept of repairing the brain with growth factors has been pursued for many years in a variety of neurodegenerative diseases including primarily Parkinson's disease (PD) using glial cell line-derived neurotrophic factor (GDNF). This neurotrophic factor was discovered in 1993 and shown to have selective effects on promoting survival and regeneration of certain populations of neurons including the dopaminergic nigrostriatal pathway. These observations led to a series of clinical trials in PD patients including using infusions or gene delivery of GDNF or the related growth factor, neurturin (NRTN). Initial studies, some of which were open label, suggested that this approach could be of value in PD when the agent was injected into the putamen rather than the cerebral ventricles. In subsequent double-blind, placebo-controlled trials, the most recent reporting in 2019, treatment with GDNF did not achieve its primary end point. As a result, there has been uncertainty as to whether GDNF (and by extrapolation, related GDNF family neurotrophic factors) has merit in the future treatment of PD. To critically appraise the existing work and its future, a special workshop was held to discuss and debate this issue. This paper is a summary of that meeting with recommendations on whether there is a future for this therapeutic approach and also what any future PD trial involving GDNF and other GDNF family neurotrophic factors should consider in its design.
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| 24. |
- Kukkola, HL, et al.
(författare)
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Lymphomas in cartilage-hair hypoplasia - A case series of 16 patients reveals advanced stage DLBCL as the most common form
- 2022
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Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 13, s. 1004694-
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Tidskriftsartikel (refereegranskat)abstract
- Patients with cartilage-hair hypoplasia (CHH) have an increased risk of malignancy, particularly non-Hodgkin lymphoma and basal cell carcinoma. The characteristics, clinical course, response to therapy and outcome of lymphomas in CHH remains unexplored.MethodsWe assessed clinical features of lymphoma cases among Finnish patients with CHH. Data were collected from the Finnish Cancer Registry, hospital records, the National Medical Databases and Cause-of-Death Registry of Statistics Finland.ResultsAmong the 160 CHH patients, 16 (6 men, 10 women) were diagnosed with lymphoma during 1953-2016. Lymphoma was diagnosed in young adulthood (median age 26.4 years, range from 6.4 to 69.5 years), mostly in advanced stage. The most common lymphoma type was diffuse large cell B-cell lymphoma (DLBCL) (6/16, 38%). Eight patients received chemotherapy (8/16, 50%), and two of them survived. Standard lymphoma chemotherapy regimens were administered in the majority of cases. Altogether, eleven CHH patients died due to lymphomas (11/16, 69%). In almost all surviving lymphoma patients, the diagnosis was made either during routine follow-up or after evaluation for non-specific mild symptoms. Search for CHH-related clinical predictors demonstrated higher prevalence of recurrent respiratory infections, in particular otitis media, and Hirschsprung disease in patients with lymphoma. However, three patients had no clinical signs of immunodeficiency prior to lymphoma diagnosis.ConclusionDLBCL is the most common type of lymphoma in CHH. The outcome is poor probably due to advanced stage of lymphoma at the time of diagnosis. Other CHH-related manifestations poorly predicted lymphoma development, implying that all CHH patients should be regularly screened for malignancy.
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| 25. |
- Lahivaara, Timo, et al.
(författare)
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Estimation of groundwater storage from seismic data using deep learning
- 2019
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Ingår i: Geophysical Prospecting. - : WILEY. - 0016-8025 .- 1365-2478. ; 67:8, s. 2115-2126
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Tidskriftsartikel (refereegranskat)abstract
- Convolutional neural networks can provide a potential framework to characterize groundwater storage from seismic data. Estimation of key components, such as the amount of groundwater stored in an aquifer and delineate water table level, from active-source seismic data are performed in this study. The data to train, validate and test the neural networks are obtained by solving wave propagation in a coupled poroviscoelastic-elastic media. A discontinuous Galerkin method is applied to model wave propagation, whereas a deep convolutional neural network is used for the parameter estimation problem. In the numerical experiment, the primary unknowns estimated are the amount of stored groundwater and water table level, while the remaining parameters, assumed to be of less of interest, are marginalized in the convolutional neural network-based solution. Results, obtained through synthetic data, illustrate the potential of deep learning methods to extract additional aquifer information from seismic data, which otherwise would be impossible based on a set of reflection seismic sections or velocity tomograms.
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| 26. |
- Oresic, Matej, 1967-, et al.
(författare)
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Phospholipids and insulin resistance in psychosis : A lipidomics study of twin pairs discordant for schizophrenia
- 2012
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Ingår i: Genome Medicine. - : BioMed Central. - 1756-994X. ; 4:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Several theories have been proposed to conceptualize the pathological processes inherent to schizophrenia. The 'prostaglandin deficiency' hypothesis postulates that defective enzyme systems converting essential fatty acids to prostaglandins lead to diminished levels of prostaglandins, which in turn affect synaptic transmission.Methods: Here we sought to determine the lipidomic profiles associated with schizophrenia in twin pairs discordant for schizophrenia as well as unaffected twin pairs. The study included serum samples from 19 twin pairs discordant for schizophrenia (mean age 51 +/- 10 years; 7 monozygotic pairs; 13 female pairs) and 34 age and gender matched healthy twins as controls. Neurocognitive assessment data and gray matter density measurements taken from high-resolution magnetic resonance images were also obtained. A lipidomics platform using ultra performance liquid chromatography coupled to time-of-flight mass spectrometry was applied for the analysis of serum samples.Results: In comparison to their healthy co-twins, the patients had elevated triglycerides and were more insulin resistant. They had diminished lysophosphatidylcholine levels, which associated with decreased cognitive speed.Conclusions: Our findings may be of pathophysiological relevance since lysophosphatidylcholines, byproducts of phospholipase A2-catalyzed phospholipid hydrolysis, are preferred carriers of polyunsaturated fatty acids across the blood-brain barrier. Furthermore, diminishment of lysophosphatidylcholines suggests that subjects at risk of schizophrenia may be more susceptible to infections. Their association with cognitive speed supports the view that altered neurotransmission in schizophrenia may be in part mediated by reactive lipids such as prostaglandins.
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| 27. |
- Pilotto, Francesca, et al.
(författare)
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Meta-analysis of multidecadal biodiversity trends in Europe
- 2020
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Local biodiversity trends over time are likely to be decoupled from global trends, as local processes may compensate or counteract global change. We analyze 161 long-term biological time series (15-91 years) collected across Europe, using a comprehensive dataset comprising ~6,200 marine, freshwater and terrestrial taxa. We test whether (i) local long-term biodiversity trends are consistent among biogeoregions, realms and taxonomic groups, and (ii) changes in biodiversity correlate with regional climate and local conditions. Our results reveal that local trends of abundance, richness and diversity differ among biogeoregions, realms and taxonomic groups, demonstrating that biodiversity changes at local scale are often complex and cannot be easily generalized. However, we find increases in richness and abundance with increasing temperature and naturalness as well as a clear spatial pattern in changes in community composition (i.e. temporal taxonomic turnover) in most biogeoregions of Northern and Eastern Europe. The global biodiversity decline might conceal complex local and group-specific trends. Here the authors report a quantitative synthesis of longterm biodiversity trends across Europe, showing how, despite overall increase in biodiversity metric and stability in abundance, trends differ between regions, ecosystem types, and taxa.
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| 32. |
- Roitto, M., et al.
(författare)
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Apoplastic and total peroxidase activities in Scots pine needles at subarctic polluted sites
- 1999
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Ingår i: European journal of forest pathology. - : Blackwell. - 0300-1237. ; 29, s. 399-410
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Tidskriftsartikel (refereegranskat)abstract
- A gradient survey was carried out in order to compare peroxidase activity in Scots pine (Pinus sylvestris) needles in relation to distance from the industrial centre of Monchegorsk, on the Kola Peninsula in north-western Russia. Apoplastic and total peroxidase activity and sulphur (S), nickel (Ni) and copper (Cu) content in the needles of mature trees were measured on seven plots located between 10 and 110 km from the pollution source. Peroxidase activities in both current- and previous-year needles increased towards the smelters and showed a positive correlation with needle S, Cu and Ni concentrations. Total peroxidase activities showed a more obvious relationship to the pollution gradient in winter than in autumn. The element contents in the current year needles averaged 1649 ppm (S), 128 ppm (Ni) and 118 ppm (Cu) close to the smelters, 1212 ppm (S), 37 ppm (Ni) and 67 ppm (Cu) at adistance of 40 km and 831 ppm (S), 7 ppm (Ni) and 1 ppm (Cu) at the most distant sampling plot. This study showed that both the apoplastic and total peroxidase activities responded to heavy metal and sulphur pollution up to 40 km from the smelters in winter, which indicated an increased oxidative stress in this area. The harsh climate conditions and the high pollution levels may have had additive effects. However, as peroxidases are considered a general indicator of stress, it is not possible to evaluate the extent to which single pollutants contribute to this enzyme activity.
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| 33. |
- Vepsäläinen, K., et al.
(författare)
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Inhibitor development in previously untreated patients with severe haemophilia A : a nationwide multicentre study in Finland
- 2016
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Ingår i: Haemophilia. - : Wiley. - 1351-8216. ; 22:5, s. 721-729
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Currently the most serious treatment complication of haemophilia is the inhibitor development (ID), i.e. neutralizing antibody development. Aim: This nationwide multicentre study in Finland evaluated the incidence and risk factors of ID in previously untreated patients (PUPs) with severe haemophilia A (FVIII:C < 0.01 IU mL−1). Methods: We enrolled all PUPs (N = 62) born between June 1994 and May 2013 with at least 75 exposure days (EDs) to screen ID during follow-up extending to September 2013. Results: Thirteen ID (21% of 62) occurred; 10 (16% of 62) with high titre. Fifty-one patients (82%) were on primary prophylaxis (regular prophylaxis before the age of 2 and before the first joint bleed) from the median age of 11.4 months, 90% via a central venous access device. The initial product was rFVIII in 63% and pd-FVIII in 37%, moreover in 24% pd-FVIII was switched to rFVIII concentrate during the 75 EDs. Non-transient inhibitors developed in 9/51 (17.6%; 13.7% high titre) children with primary and in 4/11 (36.4%; 27.3% high titre) patients with secondary prophylaxis (P = 0.24). Overall, 74% had a high-risk genotype similarly distributed among the prophylaxis groups. The history of a major bleed enhanced ID (aHR, 4.0; 95% CI, 1.2–13.7), whereas FVIII treatment intensity or source and early implantation of ports did not increase ID risk. Conclusion: The cumulative incidence of ID was low notwithstanding prevalent high-risk mutations. Despite patient-related risk factors, our management involving early intensive primary prophylaxis via ports helps to prevent bleeds and lower the incidence of inhibitors.
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