| 1. |
- Kaufmann, Tobias, et al.
(författare)
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Common brain disorders are associated with heritable patterns of apparent aging of the brain
- 2019
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Ingår i: Nature Neuroscience. - : Nature Publishing Group. - 1097-6256 .- 1546-1726. ; 22:10, s. 1617-
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Tidskriftsartikel (refereegranskat)abstract
- Common risk factors for psychiatric and other brain disorders are likely to converge on biological pathways influencing the development and maintenance of brain structure and function across life. Using structural MRI data from 45,615 individuals aged 3-96 years, we demonstrate distinct patterns of apparent brain aging in several brain disorders and reveal genetic pleiotropy between apparent brain aging in healthy individuals and common brain disorders.
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| 2. |
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| 3. |
- Dima, Danai, et al.
(författare)
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Subcortical volumes across the lifespan : Data from 18,605 healthy individuals aged 3-90 years.
- 2022
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Ingår i: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 43:1, s. 452-469
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Tidskriftsartikel (refereegranskat)abstract
- Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.
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| 4. |
- Frangou, Sophia, et al.
(författare)
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Cortical thickness across the lifespan : Data from 17,075 healthy individuals aged 3-90 years
- 2022
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Ingår i: Human Brain Mapping. - : John Wiley & Sons. - 1065-9471 .- 1097-0193. ; 43:1, s. 431-451
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Tidskriftsartikel (refereegranskat)abstract
- Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3-90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes.
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| 5. |
- Hornborg, Sara, et al.
(författare)
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Environmental and nutritional perspectives of algae
- 2023
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Algae have gained increasing attention as promising food from both an environmental and nutritional perspective. However, current understanding is still limited. This report summarizes the status of knowledge for this emerging sector, focusing on micro- and macroalgae species most relevant for Europe (particularly Sweden). Environmental impacts, with focus on climate, are evaluated through literature reviews and analysis of existing life cycle assessments (LCAs), and nutritional potential in the form of data compilation and calculation of nutrient density scores. Overall, findings reveal that current data is incomplete and of poor representativeness. Most LCAs are not performed on commercial production, but at pilot or experimental scale, why often only indicative drivers for greenhouse gas emissions may be identified. For microalgae, there is a wide diversity of production systems in different conditions across the globe. Based on the data at hand, energy use is a key hotspot across most studies for this production, driven by the requirements of different types of systems and species, and to location. For macroalgae production, despite poor representativeness of especially green and red macroalgae, key aspects for minimizing greenhouse gas emissions are associated with energy consumption and use of materials for farming such as ropes. No LCA exists on wild harvested macroalgae, representing the largest production volume in Europe (>95%); large-scale wild harvest may also be associated with risks to ecosystems unless suitable management is enforced. Significant data gaps also exist in food composition databases regarding nutrient and heavy metal content in algae (e.g., vitamins and omega-3 fatty acids). When available, nutrient content was found to be highly variable within and across species, but overall, the evaluation of nutritional quality indicated that algae may be a considerable source of minerals and vitamin B12. The contribution of fiber and protein is generally minimal in a 5 g dry weight portion of macroalgae; microalgae may have higher protein content, and also fat. However, excessive amounts of iodine and several heavy metals may be represented even in very small amounts of unprocessed macroalgae. In summary, the suggested potential of farmed algae as a sustainable food resource is overall strengthened by its generally low carbon footprint during production compared to other food raw materials. However, more input data are needed to fill data gaps regarding both environmental impacts and nutrient quality, and effects from different processing, as well as improved understanding of nutrient and contaminant bioavailability. Pending further research, careful considerations of risks and benefits associated with algae production and consumption should be applied.
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| 6. |
- Karlsson, MariAnne, 1956, et al.
(författare)
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D1.1. Integrated Framework. Deliverable to the MeBeSafe project
- 2018
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The MeBeSafe project intends to develop, implement and validate interventions that direct road users (drivers and cyclists) towards safer behaviour in common traffic situations which carry an elevated risk. More specifically, the aim is to change habitual traffic behaviour using different nudging interventions, i.e. subconsciously pushing road users in a desired direction without being prohibitive against alternative choices of action. The project will also compare different ways of coaching and evaluate the effect of a combination of nudging and coaching. This deliverable, D1.1 Integrated Framework, describes the work completed within WP1 of the MeBeSafe project. Based on literature reviews, interviews with academic and non-academic experts, discussions and workshops, the deliverable: (i) describes the key characteristics of nudging and coaching respectively; (ii) presents a framework that integrates the two, taking into consideration (in particular) time and frequency; (iii) describes underlying theories and models of relevance for understanding road user behaviour; (iii) explains road user profiles or characteristics of relevance to consider in the design of the interventions (i.e., in WP2, WP3, and WP4), as well as the design and interpretation of the outcome of the field trials (in WP5); and (iv) presents design considerations, i.e. factors that should be observed when improving on the initial ideas and further develop the design of the nudging and coaching interventions. More detailed design guidelines must be developed as part of the work to be completed in WP2, WP3, and WP4.
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| 7. |
- Kauppi, Anna M., et al.
(författare)
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Metabolites in Blood for Prediction of Bacteremic Sepsis in the Emergency Room
- 2016
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Ingår i: PLOS ONE. - : Public Library Science. - 1932-6203. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- A metabolomics approach for prediction of bacteremic sepsis in patients in the emergency room (ER) was investigated. In a prospective study, whole blood samples from 65 patients with bacteremic sepsis and 49 ER controls were compared. The blood samples were analyzed using gas chromatography coupled to time-of-flight mass spectrometry. Multivariate and logistic regression modeling using metabolites identified by chromatography or using conventional laboratory parameters and clinical scores of infection were employed. A predictive model of bacteremic sepsis with 107 metabolites was developed and validated. The number of metabolites was reduced stepwise until identifying a set of 6 predictive metabolites. A 6-metabolite predictive logistic regression model showed a sensitivity of 0.91(95% CI 0.69-0.99) and a specificity 0.84 (95% CI 0.58-0.94) with an AUC of 0.93 (95% CI 0.89-1.01). Myristic acid was the single most predictive metabolite, with a sensitivity of 1.00 (95% CI 0.85-1.00) and specificity of 0.95 (95% CI 0.74-0.99), and performed better than various combinations of conventional laboratory and clinical parameters. We found that a metabolomics approach for analysis of acute blood samples was useful for identification of patients with bacteremic sepsis. Metabolomics should be further evaluated as a new tool for infection diagnostics.
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| 8. |
- Köttgen, Anna, et al.
(författare)
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New loci associated with kidney function and chronic kidney disease
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:5, s. 376-384
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Tidskriftsartikel (refereegranskat)abstract
- Chronic kidney disease (CKD) is a significant public health problem, and recent genetic studies have identified common CKD susceptibility variants. The CKDGen consortium performed a meta-analysis of genome-wide association data in 67,093 individuals of European ancestry from 20 predominantly population-based studies in order to identify new susceptibility loci for reduced renal function as estimated by serum creatinine (eGFRcrea), serum cystatin c (eGFRcys) and CKD (eGFRcrea < 60 ml/min/1.73 m2; n = 5,807 individuals with CKD (cases)). Follow-up of the 23 new genome-wide–significant loci (P < 5 × 10−8) in 22,982 replication samples identified 13 new loci affecting renal function and CKD (in or near LASS2, GCKR, ALMS1, TFDP2, DAB2, SLC34A1, VEGFA, PRKAG2, PIP5K1B, ATXN2, DACH1, UBE2Q2 and SLC7A9) and 7 loci suspected to affect creatinine production and secretion (CPS1, SLC22A2, TMEM60, WDR37, SLC6A13, WDR72 and BCAS3). These results further our understanding of the biologic mechanisms of kidney function by identifying loci that potentially influence nephrogenesis, podocyte function, angiogenesis, solute transport and metabolic functions of the kidney.
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| 9. |
- Lango Allen, Hana, et al.
(författare)
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Hundreds of variants clustered in genomic loci and biological pathways affect human height.
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 467:7317, s. 832-8
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Tidskriftsartikel (refereegranskat)abstract
- Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P<0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
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| 10. |
- Laraia, Luca, et al.
(författare)
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The cholesterol transfer protein GRAMD1A regulates autophagosome biogenesis
- 2019
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Ingår i: Nature Chemical Biology. - : Nature Publishing Group. - 1552-4450 .- 1552-4469. ; 15:7, s. 710-720
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Tidskriftsartikel (refereegranskat)abstract
- Autophagy mediates the degradation of damaged proteins, organelles and pathogens, and plays a key role in health and disease. Thus, the identification of new mechanisms involved in the regulation of autophagy is of major interest. In particular, little is known about the role of lipids and lipid-binding proteins in the early steps of autophagosome biogenesis. Using target-agnostic, high-content, image-based identification of indicative phenotypic changes induced by small molecules, we have identified autogramins as a new class of autophagy inhibitor. Autogramins selectively target the recently discovered cholesterol transfer protein GRAM domain-containing protein 1A (GRAMD1A, which had not previously been implicated in autophagy), and directly compete with cholesterol binding to the GRAMD1A StART domain. GRAMD1A accumulates at sites of autophagosome initiation, affects cholesterol distribution in response to starvation and is required for autophagosome biogenesis. These findings identify a new biological function of GRAMD1A and a new role for cholesterol in autophagy.
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