| 1. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 6. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 7. |
- Lembrechts, Jonas J., et al.
(författare)
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SoilTemp : A global database of near-surface temperature
- 2020
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Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 26:11, s. 6616-6629
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Tidskriftsartikel (refereegranskat)abstract
- Current analyses and predictions of spatially explicit patterns and processes in ecology most often rely on climate data interpolated from standardized weather stations. This interpolated climate data represents long-term average thermal conditions at coarse spatial resolutions only. Hence, many climate-forcing factors that operate at fine spatiotemporal resolutions are overlooked. This is particularly important in relation to effects of observation height (e.g. vegetation, snow and soil characteristics) and in habitats varying in their exposure to radiation, moisture and wind (e.g. topography, radiative forcing or cold-air pooling). Since organisms living close to the ground relate more strongly to these microclimatic conditions than to free-air temperatures, microclimatic ground and near-surface data are needed to provide realistic forecasts of the fate of such organisms under anthropogenic climate change, as well as of the functioning of the ecosystems they live in. To fill this critical gap, we highlight a call for temperature time series submissions to SoilTemp, a geospatial database initiative compiling soil and near-surface temperature data from all over the world. Currently, this database contains time series from 7,538 temperature sensors from 51 countries across all key biomes. The database will pave the way toward an improved global understanding of microclimate and bridge the gap between the available climate data and the climate at fine spatiotemporal resolutions relevant to most organisms and ecosystem processes.
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| 8. |
- Amare, Azmeraw, et al.
(författare)
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Association of Polygenic Score and the involvement of Cholinergic and Glutamatergic Pathways with Lithium Treatment Response in Patients with Bipolar Disorder.
- 2023
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Ingår i: Research square. - : Research Square Platform LLC.
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Tidskriftsartikel (refereegranskat)abstract
- Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N=2,367) and replicated in the combined PsyCourse (N=89) and BipoLife (N=102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P<����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������.
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| 9. |
- Amare, Azmeraw T, et al.
(författare)
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Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder.
- 2023
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Ingår i: Molecular psychiatry. - 1476-5578. ; 28, s. 5251-5261
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Tidskriftsartikel (refereegranskat)abstract
- Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental healthdisorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N=2367) and replicated in the combined PsyCourse (N=89) and BipoLife (N=102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P<0.05. Li+PGS was positively associated with lithium treatment response in the ConLi+Gen cohort, in both the categorical (P=9.8×10-12, R2=1.9%) and continuous (P=6.4×10-9, R2=2.6%) outcomes. Compared to bipolar patients in the 1st decile of the risk distribution, individuals in the 10th decile had 3.47-fold (95%CI: 2.22-5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P=3.9×10-4, R2=0.9%), but not for the continuous outcome (P=0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li+PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment.
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| 10. |
- de Rojas, I., et al.
(författare)
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Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
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| 11. |
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| 12. |
- Hagara, Jakub, et al.
(författare)
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Novel highly substituted thiophene-based n-type organic semiconductor : structural study, optical anisotropy and molecular control
- 2020
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Ingår i: CrystEngComm. - : Royal Society of Chemistry. - 1466-8033. ; 22:42, s. 7095-7103
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Tidskriftsartikel (refereegranskat)abstract
- Oligothiophenes and their functionalized derivatives have been shown to be a viable option for high-performance organic electronic devices. The functionalization of oligothiophene-based materials allows further tailoring of their properties for specific applications. We have synthesized a new thiophene-based molecule 1-[5'-(2-naphthyl)-2,2'-bithiophen-5-yl]hexan-1-one (NCOH), and we have studied the optical and structural properties of NCOH thin films. NCOH is a highly substituted member of the oligothiophene family, designed to improve its molecular stacking, where the presence of an electron-withdrawing group enhances its electron transport capabilities. Employing in situ and time-resolved grazing-incidence wide-angle X-ray scattering (GIWAXS) measurements, we determined the NCOH thin film crystallographic structure and its evolution starting from the early stages of the film growth. We observed strong optical anisotropy resulting from a highly oriented crystallographic structure. Additionally, we investigated the substrate-induced changes of the molecular orientation utilizing the few-layer MoS2 with different orientations of the atomic layers. This study, with its primary focus on the fundamentally important n-type molecular semiconductor, contributes to the field of organic-based (opto-)electronics.
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| 13. |
- Kalman, Janos L, et al.
(författare)
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Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study.
- 2019
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Ingår i: Bipolar disorders. - : Wiley. - 1399-5618 .- 1398-5647. ; 21:1, s. 68-75
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Tidskriftsartikel (refereegranskat)abstract
- Bipolar disorder (BD) with early disease onset is associated with an unfavorable clinical outcome and constitutes a clinically and biologically homogenous subgroup within the heterogeneous BD spectrum. Previous studies have found an accumulation of early age at onset (AAO) in BD families and have therefore hypothesized that there is a larger genetic contribution to the early-onset cases than to late onset BD. To investigate the genetic background of this subphenotype, we evaluated whether an increased polygenic burden of BD- and schizophrenia (SCZ)-associated risk variants is associated with an earlier AAO in BD patients.A total of 1995 BD type 1 patients from the Consortium of Lithium Genetics (ConLiGen), PsyCourse and Bonn-Mannheim samples were genotyped and their BD and SCZ polygenic risk scores (PRSs) were calculated using the summary statistics of the Psychiatric Genomics Consortium as a training data set. AAO was either separated into onset groups of clinical interest (childhood and adolescence [≤18years] vs adulthood [>18years]) or considered as a continuous measure. The associations between BD- and SCZ-PRSs and AAO were evaluated with regression models.BD- and SCZ-PRSs were not significantly associated with age at disease onset. Results remained the same when analyses were stratified by site of recruitment.The current study is the largest conducted so far to investigate the association between the cumulative BD and SCZ polygenic risk and AAO in BD patients. The reported negative results suggest that such a polygenic influence, if there is any, is not large, and highlight the importance of conducting further, larger scale studies to obtain more information on the genetic architecture of this clinically relevant phenotype.
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| 14. |
- Kattge, Jens, et al.
(författare)
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TRY plant trait database - enhanced coverage and open access
- 2020
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Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
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Tidskriftsartikel (refereegranskat)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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| 15. |
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| 17. |
- Amare, Azmeraw T, et al.
(författare)
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Association of Polygenic Score for Schizophrenia and HLA Antigen and Inflammation Genes With Response to Lithium in Bipolar Affective Disorder: A Genome-Wide Association Study.
- 2018
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 75:1, s. 65-74
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Tidskriftsartikel (refereegranskat)abstract
- Lithium is a first-line mood stabilizer for the treatment of bipolar affective disorder (BPAD). However, the efficacy of lithium varies widely, with a nonresponse rate of up to 30%. Biological response markers are lacking. Genetic factors are thought to mediate treatment response to lithium, and there is a previously reported genetic overlap between BPAD and schizophrenia (SCZ).To test whether a polygenic score for SCZ is associated with treatment response to lithium in BPAD and to explore the potential molecular underpinnings of this association.A total of 2586 patients with BPAD who had undergone lithium treatment were genotyped and assessed for long-term response to treatment between 2008 and 2013. Weighted SCZ polygenic scores were computed at different P value thresholds using summary statistics from an international multicenter genome-wide association study (GWAS) of 36989 individuals with SCZ and genotype data from patients with BPAD from the Consortium on Lithium Genetics. For functional exploration, a cross-trait meta-GWAS and pathway analysis was performed, combining GWAS summary statistics on SCZ and response to treatment with lithium. Data analysis was performed from September 2016 to February 2017.Treatment response to lithium was defined on both the categorical and continuous scales using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. The effect measures include odds ratios and the proportion of variance explained.Of the 2586 patients in the study (mean [SD] age, 47.2 [13.9] years), 1478 were women and 1108 were men. The polygenic score for SCZ was inversely associated with lithium treatment response in the categorical outcome, at a threshold P<5×10-2. Patients with BPAD who had a low polygenic load for SCZ responded better to lithium, with odds ratios for lithium response ranging from 3.46 (95% CI, 1.42-8.41) at the first decile to 2.03 (95% CI, 0.86-4.81) at the ninth decile, compared with the patients in the 10th decile of SCZ risk. In the cross-trait meta-GWAS, 15 genetic loci that may have overlapping effects on lithium treatment response and susceptibility to SCZ were identified. Functional pathway and network analysis of these loci point to the HLA antigen complex and inflammatory cytokines.This study provides evidence for a negative association between high genetic loading for SCZ and poor response to lithium in patients with BPAD. These results suggest the potential for translational research aimed at personalized prescribing of lithium.
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| 18. |
- Andréasson, Karin, et al.
(författare)
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Body mass index in adolescence, risk of type 2 diabetes and associated complications: A nationwide cohort study of men
- 2022
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Ingår i: EClinicalMedicine. - : Elsevier BV. - 2589-5370. ; 46
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Tidskriftsartikel (refereegranskat)abstract
- Background Obesity is a predominant factor in development of type 2 diabetes but to which extent adolescent obesity influences adult diabetes is unclear. We investigated the association between body mass index (BMI) in young men and subsequent type 2 diabetes and how, in diagnosed diabetes, adolescent BMI relates to glycemic control and diabetes complications. Methods Baseline data from the Swedish Conscript Register for men drafted 1968-2005 was combined with data from the National Diabetes and Patient registries. Diabetes risk was estimated through Cox regression and Kaplan-Meier survival estimates. Relationships between BMI, glycemic control and diabetes complications were assessed through multiple linear and logistic regression. Findings Among 1,647,826 men, 63,957 (3.88%) developed type 2 diabetes over a median follow-up of 29.0 years (IQR[21.0-37.0]). The risk of diabetes within 40 years after conscription was nearly 40% in individuals with adolescent BMI >= 35 kg/m(2). Compared to BMI 18.5-<20 kg/m(2) (reference), diabetes risk increased in a linear fashion from HR 1.18(95%CI 1.15-1.21) for BMI 20-<22.5 kg/m(2) to HR 15.93(95%CI 14.88-17.05) for BMI >= 35 kg/m(2), and a difference in age at onset of 11.4 years was seen. Among men who developed diabetes, higher adolescent BMI was associated with higher HbA1c levels and albuminuria rates. Interpretation Rising adolescent BMI was associated with increased risk of type 2 diabetes diagnosed at a younger age, with poorer metabolic control, and a greater prevalence of albuminuria, all suggestive of worse prognosis. Copyright (C) 2022 The Authors. Published by Elsevier Ltd.
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| 19. |
- Bergström, Göran, et al.
(författare)
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Self-report tool for identification of individuals with coronary atherosclerosis : the Swedish cardiopulmonary bioimage study
- 2024
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Ingår i: Journal of the American Heart Association. - : John Wiley & Sons. - 2047-9980. ; 13:14
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Coronary atherosclerosis detected by imaging is a marker of elevated cardiovascular risk. However, imaging involves large resources and exposure to radiation. The aim was, therefore, to test whether nonimaging data, specifically data that can be self-reported, could be used to identify individuals with moderate to severe coronary atherosclerosis.METHODS AND RESULTS: We used data from the population-based SCAPIS (Swedish CardioPulmonary BioImage Study) in individuals with coronary computed tomography angiography (n=25 182) and coronary artery calcification score (n=28 701), aged 50 to 64 years without previous ischemic heart disease. We developed a risk prediction tool using variables that could be assessed from home (self-report tool). For comparison, we also developed a tool using variables from laboratory tests, physical examinations, and self-report (clinical tool) and evaluated both models using receiver operating characteristic curve analysis, external validation, and benchmarked against factors in the pooled cohort equation. The self-report tool (n=14 variables) and the clinical tool (n=23 variables) showed high-to-excellent discriminative ability to identify a segment involvement score ≥4 (area under the curve 0.79 and 0.80, respectively) and significantly better than the pooled cohort equation (area under the curve 0.76, P<0.001). The tools showed a larger net benefit in clinical decision-making at relevant threshold probabilities. The self-report tool identified 65% of all individuals with a segment involvement score ≥4 in the top 30% of the highest-risk individuals. Tools developed for coronary artery calcification score ≥100 performed similarly.CONCLUSIONS: We have developed a self-report tool that effectively identifies individuals with moderate to severe coronary atherosclerosis. The self-report tool may serve as prescreening tool toward a cost-effective computed tomography-based screening program for high-risk individuals.
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| 20. |
- Bergström, Göran, et al.
(författare)
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Self-Report Tool for Identification of Individuals With Coronary Atherosclerosis : The Swedish CardioPulmonary BioImage Study
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Ingår i: Journal of the American Heart Association. - 2047-9980. ; , s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Coronary atherosclerosis detected by imaging is a marker of elevated cardiovascular risk. However, imaging involves large resources and exposure to radiation. The aim was, therefore, to test whether nonimaging data, specifically data that can be self-reported, could be used to identify individuals with moderate to severe coronary atherosclerosis.METHODS AND RESULTS: We used data from the population-based SCAPIS (Swedish CardioPulmonary BioImage Study) in individuals with coronary computed tomography angiography (n=25 182) and coronary artery calcification score (n=28 701), aged 50 to 64 years without previous ischemic heart disease. We developed a risk prediction tool using variables that could be assessed from home (self-report tool). For comparison, we also developed a tool using variables from laboratory tests, physical examinations, and self-report (clinical tool) and evaluated both models using receiver operating characteristic curve analysis, external validation, and benchmarked against factors in the pooled cohort equation. The self-report tool (n=14 variables) and the clinical tool (n=23 variables) showed high-to-excellent discriminative ability to identify a segment involvement score ≥4 (area under the curve 0.79 and 0.80, respectively) and significantly better than the pooled cohort equation (area under the curve 0.76, P<0.001). The tools showed a larger net benefit in clinical decision-making at relevant threshold probabilities. The self-report tool identified 65% of all individuals with a segment involvement score ≥4 in the top 30% of the highest-risk individuals. Tools developed for coronary artery calcification score ≥100 performed similarly. CONCLUSIONS: We have developed a self-report tool that effectively identifies individuals with moderate to severe coronary atherosclerosis. The self-report tool may serve as prescreening tool toward a cost-effective computed tomography-based screening program for high-risk individuals.
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| 21. |
- Bergström, Lena, et al.
(författare)
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Effekter av havsbaserad vindkraft på marint liv : En syntesrapport om kunskapsläget 2021
- 2022
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Att öka tillgången på förnybar energi är nödvändigt för att motverka klimatförändringarna. Här förväntas havsbaserad vindkraft ha en viktig roll. Samtidigt medför planer på att bygga ut havsbaserad vindkraft viktiga frågeställningar kring hur marint liv och biologisk mångfald kan påverkas. I den här rapporten sammanställs det nuvarande kunskapsläget om hur havsbaserad vindkraft skulle kunna påverka marint liv, med fokus på svenska havsområden. Temamässigt omfattar rapporten bottennära miljöer, fisk, marina däggdjur och sjöfågel. Den strävar även efter att belysa kunskapsläget kring kumulativa effekter, samt frågor om under vilka förutsättningar havsbaserad vindkraft skulle kunna gynna marint liv.Bedömningarna beaktar även hur det tekniska utförandet har utvecklats, till exempel när det gäller vindparkernas utformning och dimensionering. Planeringen idag omfattar större vindparker och kraftverk, och bottenfasta vindkraftverk kan lokaliseras på allt större djup. De har hittills främst etablerats inom djupintervallet 5–40 meter, men kan numera anläggas på omkring 40–60 meters djup. Därtill förväntas flytande fundament, som klarar ännu större djup, bli vanligare. En annan viktig aspekt är hur tillämpningen av skadelindrande åtgärder har utvecklats.Havsbaserad vindkraft förväntas påverka marint liv på olika sätt under anläggnings- och driftsfasen, varför det är relevant att tydligt särskilja dessa i riskbedömningar. Rapporten berör även effekter under avvecklingsfasen.Under anläggningsfasen, som pågår någon dag per kraftverk, kan högintensivt ljud uppstå till exempel i samband med pålning av vindkraftverkens fundament. Åtgärder för att minska skadeverkningar av högintensivt ljud är viktiga, och kan förutsättas vara standard idag. Ofta finns det även behov att förbereda havsbotten, vilket leder till spridning av sedimentpartiklar. Omfattningen av både ljud- och sedimentspridning beror på lokala förhållanden. Därför behöver de lokala förhållandena beaktas för att ta fram en mer detaljerad kännedom om risker för marint liv. I synnerhet tumlare kan påverkas negativt av höga ljudnivåer vid anläggningsfasen, med risk för hörselpåverkan och kraftiga beteendestörningar om inte skadelindrande åtgärder används. Särskilda hänsyn i lokalisering och utförande kan även behövas för sälar, samt för fisk när det gäller områden och årstider som är viktiga för deras reproduktion. Under driftsfasen, som pågår upp emot cirka 40 år, bildar vindkraftverkens fundament och eventuella erosionsskydd fasta strukturer. Detta kan ge upphov till reveffekter då ytorna skapar plats för fastsittande arter. Med tiden kan även fiskar och marina däggdjur lockas dit, om förhållandena medger det. En viktig skillnad jämfört med andra typer av rev är att fundamenten går hela vägen upp till ytan, vilket ökar tillgången på hårda substrat i hela vattenpelaren. En möjlig risk är att de nya substraten skulle kunna gynna oönskade främmande arter, även om det saknas belägg för vindparkernas roll som en sådan spridningsväg.När elen produceras genereras undervattensljud, och överföringen av el i sjökablar kan leda till ett visst mått av elektromagnetiska fält i kablarnas närhet. Effekter av dessa påverkansfaktorer har varit svåra, om inte omöjliga, att notera i fältundersökningar. En generell slutsats skulle kunna vara att, om det förekommer negativa effekter av undervattensljud och elektromagnetiska fält, så är de oftast i styrka underordnade den attraktion som kommer av reveffekten. Aktuella studier tyder sammanfattningsvis på att havsbaserad vindkraft under driftsfasen inte är ett hot mot fiskar, säl eller tumlare. Särskild hänsyn när det gäller lokalisering kan dock behövas för skyddsvärda bottenmiljöer samt sjöfågel. Vissa sjöfågelarter kommer sannolikt att undvika området där vindparken etableras. Även åtgärder för att minska dödlighet kopplad till att fåglar kolliderar med kraftverken kan vara viktiga i vissa områden. Eftersom slutsatserna baseras på studier i andra miljöer än de som kan bli aktuella i Sverige framöver är en uppföljning av miljöeffekter viktig i de parker som etableras, för att ha möjlighet att säkerställa eller vid behov revidera kunskapsläget.Utveckling av kunskapsläget När det gäller vindkraftens effekter på bottennära livsmiljöer har kunskapsläget förbättrats angående mer långsiktig påverkan, liksom hur alg- och djursamhället i vindparken förändras över tid. Med åren blir det mer och mer likt det naturliga samhället på hårda bottnar i den aktuella regionen, även om arter med långlivade larvstadier främjas relativt sett mer. I viss mån saknas kunskap om vilken påverkan som kan förväntas om man bygger på större djup och om vindkraftverken står glesare, som planeras idag. Inga studier tyder dock på att etablering av vindkraftverk är ett hot mot vegetation eller bottenlevande djur i den här typen av miljöer, så länge särskilt skyddsvärda livsmiljöer undviks.Angående fisk och fisksamhällen har förståelsen för reveffekter ökat. Forskningen har övergått till att belysa reveffekter mer ingående, från att tidigare främst bekräfta om det blir en reveffekt eller inte. Sådana studier saknas dock idag för flera svenska havsområden eftersom det inte finns vindparker där.För marina däggdjur har kunskapsläget förbättrats framför allt när det gäller förståelsen av hur sälar och tumlare uppfattar och använder sig av ljud, samt hur ljud av olika frekvens och intensitet påverkar djuren.Kunskapen som hur havsbaserad vindkraft kan påverka sjöfågel har förbättrats framför allt för kustnära områden, men bedömningar begränsas fortfarande av otillräcklig kunskap om olika sjöfågelarters utbredning och dynamik i förekomst mellan år. Det här gäller speciellt områden längre ut till havs och med större djup än 30 meter. Den internationella forskningen har varit fokuserad på att bedöma kollisionsrisk, och ny teknik har gett ökad kunskap om fåglars flyghöjder och beteenden i förhållande till vindkraftverk.Kumulativa effekterFör att göra en sammanvägd bedömning av vindkraftens miljöeffekter är det relevant att sätta de enskilda bedömningarna i ett vidare sammanhang, där även till exempel aktuell miljöstatus och effekter av annan verksamhet ingår, så som omfattningen av fiske och sjöfart. I ett sådant perspektiv skulle införandet av en vindpark kunna leda till att den totala omfattningen av påverkan antingen ökar eller minskar i ett visst område. Etableringen kan också påverka samspelet mellan arter, med efterföljande indirekta effekter i ekosystemet. Att förstå sådana sammanvägda effekter är ett fortsatt viktigt forskningsområde. Det finns även ett behov av att utveckla metoder för att skatta kumulativa effekter i samband med havsbaserad vindkraft på olika rumsliga och tidsmässiga skalor. Utgående från det befintliga kunskapsläget kan risken för att havsbaserade vindparker bidrar med negativa kumulativa effekter på havsmiljön förväntas vara låg, under förutsättning att skadelindrande åtgärder tillämpas och bästa möjliga hänsyn tas. Under anläggningsfasen innebär sådana förutsättningar att skadliga nivåer av påverkansfaktorn minimeras, och att anläggningen sker under sådana rumsliga och tidsmässiga förhållanden att risken för ansamling av känsliga populationer av fisk och marina däggdjur minimeras. Bedömningen beror på att påverkan under anläggningsfasen är tidsmässigt övergående och inte förväntas upprepas vid mer än ett tillfälle per plats. Det baseras därför också på förutsättningen att annan motsvarande verksamhet inte sker samtidigt i området. För driftsfasen innebär förutsättningarna att driften sker med sådan teknik att nivån av elektromagnetiska fält är låg och att undervattensljud inte leder till negativa effekter på fisk eller marina däggdjur, och med undantag av att det fortsatt finns oklarheter kring hur sjöfågel kan påverkas.Vid en omfattande utbyggnad kommer gradvis högre hänsyn och anpassningar för att undvika kumulativa effekter att vara motiverade. Det ställer även ökade krav på nationell och internationell samordning för att undvika risker för kumulativ påverkan i samband med anläggningsfasen, till exempel om flera vindparker anläggs parallellt. Eftersom vindkraftens långsiktiga bidrag till kumulativ påverkan är svårbedömda i dagsläget, och förväntas variera både lokalt och mellan olika havsområden, vore det mycket viktigt att följa utvecklingen över tid i sådana parker som etableras, för att öka kunskapen och skapa möjlighet att vid behov införa åtgärder för att minska risker för specifika arter.Kan vindkraften ha positiva effekter på marint liv?Forskningen innehåller även exempel på när införandet av havsbaserad vindkraft kan ha gynnat arter, eller aspekter av biologisk mångfald och ekosystemtjänster. Det finns dock en svårighet med att generalisera kring om havsbaserad vindkraft kan gynna marint liv, eftersom utfallet i hög grad beror på vindparkens lokalisering, ekologiska förutsättningar, samt vilka andra aktiviteter som förekommer i närområdet. En viktig aspekt är även att mänskliga preferenser påverkar definitionen av om viss förändring i artsammansättning är ”positiv” eller ”negativ”, eftersom det här beror på hur olika arter och ekosystemstjänster värdesätts, det vill säga vilken typ av biologisk mångfald som är önskvärd i ett visst område. Rapporten redogör för olika typer av anpassningar som har förslagits för att gynna särskilda arter i samband med havsbaserad vindkraft, även om utvecklingen av sådana naturanpassade lösningar fortfarande är i sin linda.
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| 22. |
- Butt, Linus, et al.
(författare)
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A molecular mechanism explaining albuminuria in kidney disease
- 2020
-
Ingår i: Nature Metabolism. - : Springer Nature. - 2522-5812. ; 2:5, s. 461-474
-
Tidskriftsartikel (refereegranskat)abstract
- Mammalian kidneys constantly filter large amounts of liquid, with almost complete retention of albumin and other macromolecules in the plasma. Breakdown of the three-layered renal filtration barrier results in loss of albumin into urine (albuminuria) across the wall of small renal capillaries, and is a leading cause of chronic kidney disease. However, exactly how the renal filter works and why its permeability is altered in kidney diseases is poorly understood. Here we show that the permeability of the renal filter is modulated through compression of the capillary wall. We collect morphometric data prior to and after onset of albuminuria in a mouse model equivalent to a human genetic disease affecting the renal filtration barrier. Combining quantitative analyses with mathematical modelling, we demonstrate that morphological alterations of the glomerular filtration barrier lead to reduced compressive forces that counteract filtration pressure, thereby resulting in capillary dilatation, and ultimately albuminuria. Our results reveal distinct functions of the different layers of the filtration barrier and expand the molecular understanding of defective renal filtration in chronic kidney disease.
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| 23. |
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| 24. |
- Coombes, Brandon J, et al.
(författare)
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Association of Attention-Deficit/Hyperactivity Disorder and Depression Polygenic Scores with Lithium Response: A Consortium for Lithium Genetics Study.
- 2021
-
Ingår i: Complex psychiatry. - : S. Karger AG. - 2673-3005 .- 2673-298X. ; 7:3-4, s. 80-89
-
Tidskriftsartikel (refereegranskat)abstract
- Response to lithium varies widely between individuals with bipolar disorder (BD). Polygenic risk scores (PRSs) can uncover pharmacogenomics effects and may help predict drug response. Patients (N = 2,510) with BD were assessed for long-term lithium response in the Consortium on Lithium Genetics using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. PRSs for attention-deficit/hyperactivity disorder (ADHD), major depressive disorder (MDD), and schizophrenia (SCZ) were computed using lassosum and in a model including all three PRSs and other covariates, and the PRS of ADHD (β = -0.14; 95% confidence interval [CI]: -0.24 to -0.03; p value = 0.010) and MDD (β = -0.16; 95% CI: -0.27 to -0.04; p value = 0.005) predicted worse quantitative lithium response. A higher SCZ PRS was associated with higher rates of medication nonadherence (OR = 1.61; 95% CI: 1.34-1.93; p value = 2e-7). This study indicates that genetic risk for ADHD and depression may influence lithium treatment response. Interestingly, a higher SCZ PRS was associated with poor adherence, which can negatively impact treatment response. Incorporating genetic risk of ADHD, depression, and SCZ in combination with clinical risk may lead to better clinical care for patients with BD.
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| 25. |
- de Raad, Jordi, et al.
(författare)
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Speciation and population divergence in a mutualistic seed dispersing bird
- 2022
-
Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1
-
Tidskriftsartikel (refereegranskat)abstract
- Bird-mediated seed dispersal is crucial for the regeneration and viability of ecosystems, often resulting in complex mutualistic species networks. Yet, how this mutualism drives the evolution of seed dispersing birds is still poorly understood. In the present study we combine whole genome re-sequencing analyses and morphometric data to assess the evolutionary processes that shaped the diversification of the Eurasian nutcracker (Nucifraga), a seed disperser known for its mutualism with pines (Pinus). Our results show that the divergence and phylogeographic patterns of nutcrackers resemble those of other non-mutualistic passerine birds and suggest that their early diversification was shaped by similar biogeographic and climatic processes. The limited variation in foraging traits indicates that local adaptation to pines likely played a minor role. Our study shows that close mutualistic relationships between bird and plant species might not necessarily act as a primary driver of evolution and diversification in resource-specialized birds.
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| 26. |
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| 27. |
- Gad, Helge, et al.
(författare)
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MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool
- 2014
-
Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7495, s. 215-221
-
Tidskriftsartikel (refereegranskat)abstract
- Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.
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| 28. |
- Garro, Alfredo, et al.
(författare)
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On formal cyber physical system properties modeling: a new temporal logic language and a Modelica-based solution
- 2016
-
Ingår i: 2016 IEEE International Symposium on Systems Engineering (ISSE). - : IEEE. - 9781509007936 - 9781509007943 ; , s. 112-119
-
Konferensbidrag (refereegranskat)abstract
- Modeling and Simulation methods, tools and techniques aim at supporting the different phases of the lifecycle of modern systems, going from requirements analysis to system design and operation. However, their effective application requires investigating several aspects such as the formal modeling of system requirements and the binding and automated composition between heterogeneous models (e.g. requirements models, architectural models, behavioral models). In this context, the paper presents a new formal requirement modeling language based on temporal logic, called FORM-L, and a software library, based on the Modelica language, that implements the constructs provided by FORM-L so as to enable the visual modeling of system properties as well as their verification through simulation. The effectiveness of the proposal is shown on a real case study concerning an Intermediate Cooling System.
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| 29. |
- Haesen, Stef, et al.
(författare)
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ForestClim : Bioclimatic variables for microclimate temperatures of European forests
- 2023
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Ingår i: Global Change Biology. - : John Wiley & Sons. - 1354-1013 .- 1365-2486. ; 29:11, s. 2886-2892
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Tidskriftsartikel (refereegranskat)abstract
- Microclimate research gained renewed interest over the last decade and its importance for many ecological processes is increasingly being recognized. Consequently, the call for high-resolution microclimatic temperature grids across broad spatial extents is becoming more pressing to improve ecological models. Here, we provide a new set of open-access bioclimatic variables for microclimate temperatures of European forests at 25 x 25 m2 resolution.
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| 30. |
- Herrera-Rivero, Marisol, et al.
(författare)
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Exploring the genetics of lithium response in bipolar disorders.
- 2023
-
Ingår i: Research square.
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N=2,064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II.We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism.Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II.
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| 31. |
- Herrera-Rivero, Marisol, et al.
(författare)
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Immunogenetics of lithium response and psychiatric phenotypes in patients with bipolar disorder.
- 2023
-
Ingår i: Research square.
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The link between bipolar disorder (BP) and immune dysfunction remains controversial. While epidemiological studies have long suggested an association, recent research has found only limited evidence of such a relationship. To clarify this, we investigated the contributions of immune-relevant genetic factors to the response to lithium (Li) treatment and the clinical presentation of BP. First, we assessed the association of a large collection of immune-related genes (4,925) with Li response, defined by the Retrospective Assessment of the Lithium Response Phenotype Scale (Alda scale), and clinical characteristics in patients with BP from the International Consortium on Lithium Genetics (ConLi+Gen, N = 2,374). Second, we calculated here previously published polygenic scores (PGSs) for immune-related traits and evaluated their associations with Li response and clinical features. We found several genes associated with Li response at p < 1×10- 4 values, including HAS3, CNTNAP5 and NFIB. Network and functional enrichment analyses uncovered an overrepresentation of pathways involved in cell adhesion and intercellular communication, which appear to converge on the well-known Li-induced inhibition of GSK-3β. We also found various genes associated with BP's age-at-onset, number of mood episodes, and presence of psychosis, substance abuse and/or suicidal ideation at the exploratory threshold. These included RTN4, XKR4, NRXN1, NRG1/3 and GRK5. Additionally, PGS analyses suggested serum FAS, ECP, TRANCE and cytokine ligands, amongst others, might represent potential circulating biomarkers of Li response and clinical presentation. Taken together, our results support the notion of a relatively weak association between immunity and clinically relevant features of BP at the genetic level.
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| 32. |
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| 33. |
- Hou, Liping, et al.
(författare)
-
Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder.
- 2016
-
Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 25:15, s. 3383-94
-
Tidskriftsartikel (refereegranskat)abstract
- Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behavior. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million genetic variants in 9,784 bipolar disorder patients and 30,471 controls, the largest GWAS of BD to date. In this study, to increase power we used ∼2,000 lithium-treated cases with a long-term diagnosis of BD from the Consortium on Lithium Genetics, excess controls, and analytic methods optimized for markers on the X-chromosome. In addition to four known loci, results revealed genome-wide significant associations at two novel loci: an intergenic region on 9p21.3 (rs12553324, p=5.87×10(-9); odds ratio=1.12) and markers within ERBB2 (rs2517959, p=4.53×10(-9); odds ratio=1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS.
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| 34. |
- Johansson, Veronica, et al.
(författare)
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Thinking Ahead on Deep Brain Stimulation: An Analysis of the Ethical Implications of a Developing Technology.
- 2014
-
Ingår i: AJOB Neuroscience. - : Informa UK Limited. - 2150-7740 .- 2150-7759. ; 5:1, s. 24-33
-
Tidskriftsartikel (refereegranskat)abstract
- Deep brain stimulation (DBS) is a developing technology. New generations of DBS technology are already in the pipeline, yet this particular fact has been largely ignored among ethicists interested in DBS. Focusing only on ethical concerns raised by the current DBS technology is, albeit necessary, not sufficient. Since current bioethical concerns raised by a specific technology could be quite different from the concerns it will raise a couple of years ahead, an ethical analysis should be sensitive to such alterations, or it could end up with results that soon become dated. The goal of this analysis is to address these changing bioethical concerns, to think ahead on upcoming and future DBS concerns both in terms of a changing technology and changing moral attitudes. By employing the distinction between inherent and noninherent bioethical concerns we identify and make explicit the particular limits and potentials for change within each category, respectively, including how present and upcoming bioethical concerns regarding DBS emerge and become obsolete. Many of the currently identified ethical problems with DBS, such as stimulation-induced mania, are a result of suboptimal technology. These challenges could be addressed by technical advances, while for instance perceptions of an altered body image caused by the mere awareness of having an implant may not. Other concerns will not emerge until the technology has become sophisticated enough for new uses to be realized, such as concerns on DBS for enhancement purposes. As a part of the present analysis, concerns regarding authenticity are used as an example.
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| 35. |
- Jung, Christian, et al.
(författare)
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A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention
- 2019
-
Ingår i: Journal of critical care. - : W B SAUNDERS CO-ELSEVIER INC. - 0883-9441 .- 1557-8615. ; 52, s. 141-148
-
Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed.Methods: In total, 5063 VIPs were induded in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 +/- 5 vs 7 +/- 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery.
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| 36. |
- Kelsoe, John, et al.
(författare)
-
Lithium Response in Bipolar Disorder is Associated with Focal Adhesion and PI3K-Akt Networks: A Multi-omics Replication Study.
- 2023
-
Ingår i: Research square.
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Lithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extracellular matrix (ECM), and PI3K-Akt signaling networks were associated with response to lithium. In this study, we replicated the results of our previous study using network propagation methods in a genome-wide association study of an independent sample of 2,039 patients from the International Consortium on Lithium Genetics (ConLiGen) study. We identified functional enrichment in focal adhesion and PI3K-Akt pathways, but we did not find an association with the ECM pathway. Our results suggest that deficits in the neuronal growth cone and PI3K-Akt signaling, but not in ECM proteins, may influence response to lithium in BD.
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| 37. |
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| 38. |
- Krall, Lindsay, et al.
(författare)
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Tracing the palaeoredox conditions at Forsmark, Sweden, using uranium mineral geochronology
- 2019
-
Ingår i: Chemical Geology. - 0009-2541 .- 1872-6836. ; 506, s. 68-78
-
Tidskriftsartikel (refereegranskat)abstract
- U-Pb isotope systems have been used to constrain the timing of formation, alteration, and oxidation of U minerals from the meta-granitic bedrock at Forsmark, eastern Sweden. Secondary ion mass spectrometry (SIMS) has been used to collect U-Pb data from uraninite. Discordant data suggest a ~1.8 Ga emplacement of uraninite-bearing pegmatites and an event of uraninite alteration at ~1.6 Ga. The latter age is contemporaneous with the Gothian orogeny in Scandinavia, which was associated with hydrothermal fluid circulation in the Fennoscandian Shield. Ca-uranyl silicates haiweeite and uranophane predominately formed 1.3–1.2 Ga, contemporaneous with the emplacement of the Satakunta complex of the Central Scandinavian Dolerite Group. A Palaeozoic group of Ca-U(VI)-silicates is also present, which indicates that the geochemical composition of geologic fluids was heterogeneous throughout the fracture network during this time. Low Pb concentrations in the U(VI) silicates of several samples are compatible with a recent (<100 Ma) alteration or precipitation of these minerals in connection to reaction with carbonate-rich fluids. The results support a geologically early oxidation of U(IV) to U(VI) and provide insight into the palaeoredox conditions that may impart an on-going influence on the mobility of natural U in the Forsmark fracture network.
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| 39. |
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| 40. |
- Lehtipalo, Katrianne, et al.
(författare)
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Multicomponent new particle formation from sulfuric acid, ammonia, and biogenic vapors
- 2018
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 4:12
-
Tidskriftsartikel (refereegranskat)abstract
- A major fraction of atmospheric aerosol particles, which affect both air quality and climate, form from gaseous precursors in the atmosphere. Highly oxygenated organic molecules (HOMs), formed by oxidation of biogenic volatile organic compounds, are known to participate in particle formation and growth. However, it is not well understood how they interact with atmospheric pollutants, such as nitrogen oxides (NOx) and sulfur oxides (SOx) from fossil fuel combustion, as well as ammonia (NH3) from livestock and fertilizers. Here, we show how NOx suppresses particle formation, while HOMs, sulfuric acid, and NH3 have a synergistic enhancing effect on particle formation. We postulate a novel mechanism, involving HOMs, sulfuric acid, and ammonia, which is able to closely reproduce observations of particle formation and growth in daytime boreal forest and similar environments. The findings elucidate the complex interactions between biogenic and anthropogenic vapors in the atmospheric aerosol system.
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| 41. |
- Lévy, Romain, et al.
(författare)
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Human CARMIL2 deficiency underlies a broader immunological and clinical phenotype than CD28 deficiency.
- 2023
-
Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 220:2
-
Tidskriftsartikel (refereegranskat)abstract
- Patients with inherited CARMIL2 or CD28 deficiency have defective T cell CD28 signaling, but their immunological and clinical phenotypes remain largely unknown. We show that only one of three CARMIL2 isoforms is produced and functional across leukocyte subsets. Tested mutant CARMIL2 alleles from 89 patients and 52 families impair canonical NF-κB but not AP-1 and NFAT activation in T cells stimulated via CD28. Like CD28-deficient patients, CARMIL2-deficient patients display recalcitrant warts and low blood counts of CD4+ and CD8+ memory T cells and CD4+ TREGs. Unlike CD28-deficient patients, they have low counts of NK cells and memory B cells, and their antibody responses are weak. CARMIL2 deficiency is fully penetrant by the age of 10 yr and is characterized by numerous infections, EBV+ smooth muscle tumors, and mucocutaneous inflammation, including inflammatory bowel disease. Patients with somatic reversions of a mutant allele in CD4+ T cells have milder phenotypes. Our study suggests that CARMIL2 governs immunological pathways beyond CD28.
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| 42. |
- Martin, Alma, et al.
(författare)
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In Situ Transformation of Electrospun Nanofibers into Nanofiber-Reinforced Hydrogels
- 2022
-
Ingår i: Nanomaterials. - : MDPI AG. - 2079-4991. ; 12:14
-
Tidskriftsartikel (refereegranskat)abstract
- Nanofiber-reinforced hydrogels have recently gained attention in biomedical engineering. Such three-dimensional scaffolds show the mechanical strength and toughness of fibers while benefiting from the cooling and absorbing properties of hydrogels as well as a large pore size, potentially aiding cell migration. While many of such systems are prepared by complicated processes where fibers are produced separately to later be embedded in a hydrogel, we here provide proof of concept for a one-step solution. In more detail, we produced core-shell nanofibers from the natural proteins zein and gelatin by coaxial electrospinning. Upon hydration, the nanofibers were capable of directly transforming into a nanofiber-reinforced hydrogel, where the nanofibrous structure was retained by the zein core, while the gelatin-based shell turned into a hydrogel matrix. Our nanofiber-hydrogel composite showed swelling to ~800% of its original volume and water uptake of up to ~2500% in weight. The physical integrity of the nanofiber-reinforced hydrogel was found to be significantly improved in comparison to a hydrogel system without nanofibers. Additionally, tetracycline hydrochloride was incorporated into the fibers as an antimicrobial agent, and antimicrobial activity against Staphylococcus aureus and Escherichia coli was confirmed.
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| 43. |
- Martin, Alma, et al.
(författare)
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Zein-polycaprolactone core–shell nanofibers for wound healing
- 2022
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173. ; 621
-
Tidskriftsartikel (refereegranskat)abstract
- In a previous study, we developed electrospun antimicrobial microfiber scaffolds for wound healing composed of a core of zein protein and a shell containing polyethylene oxide. While providing a promising platform for composite nanofiber design, the scaffolds showed low tensile strengths, insufficient water stability, as well as burst release of the antimicrobial drug tetracycline hydrochloride, properties which are not ideal for the use of the scaffolds as wound dressings. Therefore, the aim of the present study was to develop fibers with enhanced mechanical strength and water stability, also displaying sustained release of tetracycline hydrochloride. Zein was chosen as core material, while the shell was formed by the hydrophobic polymer polycaprolactone, either alone or in combination with polyethylene oxide. As compared to control fibers of pristine polycaprolactone, the zein-polycaprolactone fibers exhibited a reduced diameter and hydrophobicity, which is beneficial for cell attachment and wound closure. Such fibers also demonstrated sustained release of tetracycline hydrochloride, as well as water stability, ductility, high mechanical strength and fibroblast attachment, hence representing a step towards the development of biodegradable wound dressings with prolonged drug release, which can be left on the wound for a longer time.
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| 44. |
- McWhinney, Sean R, et al.
(författare)
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Association between body mass index and subcortical brain volumes in bipolar disorders-ENIGMA study in 2735 individuals.
- 2021
-
Ingår i: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 26:11, s. 6806-6819
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Tidskriftsartikel (refereegranskat)abstract
- Individuals with bipolar disorders (BD) frequently suffer from obesity, which is often associated with neurostructural alterations. Yet, the effects of obesity on brain structure in BD are under-researched. We obtained MRI-derived brain subcortical volumes and body mass index (BMI) from 1134 BD and 1601 control individuals from 17 independent research sites within the ENIGMA-BD Working Group. We jointly modeled the effects of BD and BMI on subcortical volumes using mixed-effects modeling and tested for mediation of group differences by obesity using nonparametric bootstrapping. All models controlled for age, sex, hemisphere, total intracranial volume, and data collection site. Relative to controls, individuals with BD had significantly higher BMI, larger lateral ventricular volume, and smaller volumes of amygdala, hippocampus, pallidum, caudate, and thalamus. BMI was positively associated with ventricular and amygdala and negatively with pallidal volumes. When analyzed jointly, both BD and BMI remained associated with volumes of lateral ventricles and amygdala. Adjusting for BMI decreased the BD vs control differences in ventricular volume. Specifically, 18.41% of the association between BD and ventricular volume was mediatedby BMI (Z=2.73, p=0.006). BMI was associated with similar regional brain volumes as BD, including lateral ventricles, amygdala, and pallidum. Higher BMI may in part account for larger ventricles, one of the most replicated findings in BD. Comorbidity with obesity could explain why neurostructural alterations are more pronounced in some individuals with BD. Future prospective brain imaging studies should investigate whether obesity could be a modifiable risk factor for neuroprogression.
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| 45. |
- McWhinney, Sean R, et al.
(författare)
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Diagnosis of bipolar disorders and body mass index predict clustering based on similarities in cortical thickness-ENIGMA study in 2436 individuals.
- 2022
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Ingår i: Bipolar disorders. - : Wiley. - 1399-5618 .- 1398-5647. ; 24:5, s. 509-520
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Tidskriftsartikel (refereegranskat)abstract
- Rates of obesity have reached epidemic proportions, especially among people with psychiatric disorders. While the effects of obesity on the brain are of major interest in medicine, they remain markedly under-researched in psychiatry.We obtained body mass index (BMI) and magnetic resonance imaging-derived regional cortical thickness, surface area from 836 bipolar disorders (BD) and 1600 control individuals from 14sites within the ENIGMA-BD Working Group. We identified regionally specific profiles of cortical thickness using K-means clustering and studied clinical characteristics associated with individual cortical profiles.We detected two clusters based on similarities among participants in cortical thickness. The lower thickness cluster (46.8% of the sample) showed thinner cortex, especially in the frontal and temporal lobes and was associated with diagnosis of BD, higher BMI, and older age. BD individuals in the low thickness cluster were more likely to have the diagnosis of bipolar disorder I and less likely to be treated with lithium. In contrast, clustering based on similarities in the cortical surface area was unrelated to BD or BMI and only tracked age and sex.We provide evidence that both BD and obesity are associated with similar alterations in cortical thickness, but not surface area. The fact that obesity increased the chance of having low cortical thickness could explain differences in cortical measures among people with BD. The thinner cortex in individuals with higher BMI, which was additive and similar to the BD-associated alterations, may suggest that treating obesity could lower the extent of cortical thinning in BD.
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| 46. |
- McWhinney, Sean R, et al.
(författare)
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Mega-analysis of association between obesity and cortical morphology in bipolar disorders: ENIGMA study in 2832 participants.
- 2023
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Ingår i: Psychological medicine. - 1469-8978. ; 53:14, s. 6743-6753
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is highly prevalent and disabling, especially in individuals with severe mental illness including bipolar disorders (BD). The brain is a target organ for both obesity and BD. Yet, we do not understand how cortical brain alterations in BD and obesity interact.We obtained body mass index (BMI) and MRI-derived regional cortical thickness, surface area from 1231 BD and 1601 control individuals from 13 countries within the ENIGMA-BD Working Group. We jointly modeled the statistical effects of BD and BMI on brain structure using mixed effects and tested for interaction and mediation. We also investigated the impact of medications on the BMI-related associations.BMI and BD additively impacted the structure of many of the same brain regions. Both BMI and BD were negatively associated with cortical thickness, but not surface area. In most regions the number of jointly used psychiatric medication classes remained associated with lower cortical thickness when controlling for BMI. In a single region, fusiform gyrus, about a third of the negative association between number of jointly used psychiatric medications and cortical thickness was mediated by association between the number of medications and higher BMI.We confirmed consistent associations between higher BMI and lower cortical thickness, but not surface area, across the cerebral mantle, in regions which were also associated with BD. Higher BMI in people with BD indicated more pronounced brain alterations. BMI is important for understanding the neuroanatomical changes in BD and the effects of psychiatric medications on the brain.
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| 47. |
- Medlyn, Belinda E, et al.
(författare)
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How do leaf and ecosystem measures of water-use efficiency compare?
- 2017
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Ingår i: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 216:3, s. 758-770
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Tidskriftsartikel (refereegranskat)abstract
- The terrestrial carbon and water cycles are intimately linked: the carbon cycle is driven by photosynthesis, while the water balance is dominated by transpiration, and both fluxes are controlled by plant stomatal conductance. The ratio between these fluxes, the plant water-use efficiency (WUE), is a useful indicator of vegetation function. WUE can be estimated using several techniques, including leaf gas exchange, stable isotope discrimination, and eddy covariance. Here we compare global compilations of data for each of these three techniques. We show that patterns of variation in WUE across plant functional types (PFTs) are not consistent among the three datasets. Key discrepancies include the following: leaf-scale data indicate differences between needleleaf and broadleaf forests, but ecosystem-scale data do not; leaf-scale data indicate differences between C3 and C4 species, whereas at ecosystem scale there is a difference between C3 and C4 crops but not grasslands; and isotope-based estimates of WUE are higher than estimates based on gas exchange for most PFTs. Our study quantifies the uncertainty associated with different methods of measuring WUE, indicates potential for bias when using WUE measures to parameterize or validate models, and indicates key research directions needed to reconcile alternative measures of WUE.
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| 48. |
- Moberg, Christina, et al.
(författare)
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De unga gör helt rätt när de stämmer staten
- 2022
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Ingår i: Aftonbladet. - 1103-9000.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
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| 49. |
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| 50. |
- Nääv, Åsa, et al.
(författare)
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A1M Ameliorates Preeclampsia-Like Symptoms in Placenta and Kidney Induced by Cell-Free Fetal Hemoglobin in Rabbit.
- 2015
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:5
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Tidskriftsartikel (refereegranskat)abstract
- Preeclampsia is one of the most serious pregnancy-related diseases and clinically manifests as hypertension and proteinuria after 20 gestational weeks. The worldwide prevalence is 3-8% of pregnancies, making it the most common cause of maternal and fetal morbidity and mortality. Preeclampsia lacks an effective therapy, and the only "cure" is delivery. We have previously shown that increased synthesis and accumulation of cell-free fetal hemoglobin (HbF) in the placenta is important in the pathophysiology of preeclampsia. Extracellular hemoglobin (Hb) and its metabolites induce oxidative stress, which may lead to acute renal failure and vascular dysfunction seen in preeclampsia. The human endogenous protein, α1-microglobulin (A1M), removes cell-free heme-groups and induces natural tissue repair mechanisms. Exogenously administered A1M has been shown to alleviate the effects of Hb-induced oxidative stress in rat kidneys. Here we attempted to establish an animal model mimicking the human symptoms at stage two of preeclampsia by administering species-specific cell-free HbF starting mid-gestation until term, and evaluated the therapeutic effect of A1M on the induced symptoms. Female pregnant rabbits received HbF infusions i.v. with or without A1M every second day from gestational day 20. The HbF-infused animals developed proteinuria and a significantly increased glomerular sieving coefficient in kidney that was ameliorated by co-administration of A1M. Transmission electron microscopy analysis of kidney and placenta showed both intracellular and extracellular tissue damages after HbF-treatment, while A1M co-administration resulted in a significant reduction of the structural and cellular changes. Neither of the HbF-treated animals displayed any changes in blood pressure during pregnancy. In conclusion, infusion of cell-free HbF in the pregnant rabbits induced tissue damage and organ failure similar to those seen in preeclampsia, and was restored by co-administration of A1M. This study provides preclinical evidence supporting further examination of A1M as a potential new therapy for preeclampsia.
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