| 51. |
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| 52. |
- van Dongen, J, et al.
(författare)
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DNA methylation signatures of aggression and closely related constructs: A meta-analysis of epigenome-wide studies across the lifespan
- 2021
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Ingår i: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 26:6, s. 2148-2162
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Tidskriftsartikel (refereegranskat)abstract
- DNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N = 15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha = 1.2 × 10−7; Bonferroni correction). In cord blood samples of 2425 children from five cohorts with aggression assessed at mean ages ranging from 4 to 7 years, 83% of these sites showed the same direction of association with childhood aggression (r = 0.74, p = 0.006) but no epigenome-wide significant sites were found. Top-sites (48 at a false discovery rate of 5% in the peripheral blood meta-analysis or in a combined meta-analysis of peripheral blood and cord blood) have been associated with chemical exposures, smoking, cognition, metabolic traits, and genetic variation (mQTLs). Three genes whose expression levels were associated with top-sites were previously linked to schizophrenia and general risk tolerance. At six CpGs, DNA methylation variation in blood mirrors variation in the brain. On average 44% (range = 3–82%) of the aggression–methylation association was explained by current and former smoking and BMI. These findings point at loci that are sensitive to chemical exposures with potential implications for neuronal functions. We hope these results to be a starting point for studies leading to applications as peripheral biomarkers and to reveal causal relationships with aggression and related traits.
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| 53. |
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| 54. |
- Abreu, A., et al.
(författare)
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Priorities for ocean microbiome research
- 2022
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Ingår i: Nature Microbiology. - : Springer Science and Business Media LLC. - 2058-5276. ; 7:7, s. 937-947
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Tidskriftsartikel (refereegranskat)abstract
- Studying the ocean microbiome can inform international policies related to ocean governance, tackling climate change, ocean acidification and pollution, and can help promote achievement of multiple Sustainable Development Goals. Microbial communities have essential roles in ocean ecology and planetary health. Microbes participate in nutrient cycles, remove huge quantities of carbon dioxide from the air and support ocean food webs. The taxonomic and functional diversity of the global ocean microbiome has been revealed by technological advances in sampling, DNA sequencing and bioinformatics. A better understanding of the ocean microbiome could underpin strategies to address environmental and societal challenges, including achievement of multiple Sustainable Development Goals way beyond SDG 14 'life below water'. We propose a set of priorities for understanding and protecting the ocean microbiome, which include delineating interactions between microbiota, sustainably applying resources from oceanic microorganisms and creating policy- and funder-friendly ocean education resources, and discuss how to achieve these ambitious goals.
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| 55. |
- Augestad, IL, et al.
(författare)
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Regulation of Glycemia in the Recovery Phase After Stroke Counteracts the Detrimental Effect of Obesity-Induced Type 2 Diabetes on Neurological Recovery
- 2020
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 69:9, s. 1961-1973
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Tidskriftsartikel (refereegranskat)abstract
- The interplay between obesity and type 2 diabetes (T2D) in poststroke recovery is unclear. Moreover, the impact of glucose control during the chronic phase after stroke is undetermined. We investigated whether obesity-induced T2D impairs neurological recovery after stroke by using a clinically relevant experimental design. We also investigated the potential efficacy of two clinically used T2D drugs: the dipeptidyl peptidase 4 inhibitor linagliptin and the sulfonylurea glimepiride. We induced transient middle cerebral artery occlusion (tMCAO) in T2D/obese mice (after 7 months of high-fat diet [HFD]) and age-matched controls. After stroke, we replaced HFD with standard diet for 8 weeks to mimic the poststroke clinical situation. Linagliptin or glimepiride were administered daily from 3 days after tMCAO for 8 weeks. We assessed neurological recovery weekly by upper-limb grip strength. Brain damage, neuroinflammation, stroke-induced neurogenesis, and atrophy of parvalbumin-positive (PV+) interneurons were quantified by immunohistochemistry. T2D/obesity impaired poststroke neurological recovery in association with hyperglycemia, neuroinflammation, and atrophy of PV+ interneurons. Both drugs counteracted these effects. In nondiabetic mice, only linagliptin accelerated recovery. These findings shed light on the interplay between obesity and T2D in stroke recovery. Moreover, they promote the use of rehabilitative strategies that are based on efficacious glycemia regulation, even if initiated days after stroke.
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| 56. |
- Bammer, G., et al.
(författare)
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Expertise in research integration and implementation for tackling complex problems: when is it needed, where can it be found and how can it be strengthened?
- 2020
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Ingår i: Palgrave Communications. - : Springer Science and Business Media LLC. - 2055-1045. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Expertise in research integration and implementation is an essential but often overlooked component of tackling complex societal and environmental problems. We focus on expertise relevant to any complex problem, especially contributory expertise, divided into 'knowing-that' and 'knowing-how.' We also deal with interactional expertise and the fact that much expertise is tacit. We explore three questions. First, in examining 'when is expertise in research integration and implementation required?,' we review tasks essential (a) to developing more comprehensive understandings of complex problems, plus possible ways to address them, and (b) for supporting implementation of those understandings into government policy, community practice, business and social innovation, or other initiatives. Second, in considering 'where can expertise in research integration and implementation currently be found?,' we describe three realms: (a) specific approaches, including interdisciplinarity, transdisciplinarity, systems thinking and sustainability science; (b) case-based experience that is independent of these specific approaches; and (c) research examining elements of integration and implementation, specifically considering unknowns and fostering innovation. We highlight examples of expertise in each realm and demonstrate how fragmentation currently precludes clear identification of research integration and implementation expertise. Third, in exploring 'what is required to strengthen expertise in research integration and implementation?,' we propose building a knowledge bank. We delve into three key challenges: compiling existing expertise, indexing and organising the expertise to make it widely accessible, and understanding and overcoming the core reasons for the existing fragmentation. A growing knowledge bank of expertise in research integration and implementation on the one hand, and accumulating success in addressing complex societal and environmental problems on the other, will form a virtuous cycle so that each strengthens the other. Building a coalition of researchers and institutions will ensure this expertise and its application are valued and sustained.
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| 57. |
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| 58. |
- Capasso, Raffaella, et al.
(författare)
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Mass calibration of the CODEX cluster sample using SPIDERS spectroscopy - II. The X-ray luminosity-mass relation
- 2020
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 494:2, s. 2736-2746
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Tidskriftsartikel (refereegranskat)abstract
- We perform the calibration of the X-ray luminosity-mass scaling relation on a sample of 344 CODEX clusters with z < 0.66 using the dynamics of their member galaxies. Spectroscopic follow-up measurements have been obtained from the SPIDERS survey, leading to a sample of 6658 red member galaxies. We use the Jeans equation to calculate halo masses, assuming an NFW mass profile and analysing a broad range of anisotropy profiles. With a scaling relation of the form L-X proportional to A(X)M(200c)(BX) E(z)(2)(1 + z)(gamma x), we find best-fitting parameters A(X) = 0.62(-0.06)(+0.05) (+/- 0.06) x 10(44) erg s(-)(1), B-X = 2.35(-0.18)(+0.21)(+/- 0.09), gamma(X) = -2.77(-1.05)(+1.06)(+/- 0.79), where we include systematic uncertainties in parentheses and for a pivot mass and redshift of 3 x 10(14) M-circle dot and 0.16, respectively. We compare our constraints with previous results, and we combine our sample with the SPT SZE-selected cluster subsample observed with XMM-Newton extending the validity of our results to a wider range of redshifts and cluster masses.
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| 59. |
- Chen, Hongjie, et al.
(författare)
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Large-scale cross-cancer fine-mapping of the 5p15.33 region reveals multiple independent signals
- 2021
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Ingår i: Human Genetics and Genomics Advances. - : Cell Press. - 2666-2477. ; 2:3
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWASs) have identified thousands of cancer risk loci revealing many risk regions shared across multiple cancers. Characterizing the cross-cancer shared genetic basis can increase our understanding of global mechanisms of cancer development. In this study, we collected GWAS summary statistics based on up to 375,468 cancer cases and 530,521 controls for fourteen types of cancer, including breast (overall, estrogen receptor [ER]-positive, and ER-negative), colorectal, endometrial, esophageal, glioma, head/neck, lung, melanoma, ovarian, pancreatic, prostate, and renal cancer, to characterize the shared genetic basis of cancer risk. We identified thirteen pairs of cancers with statistically significant local genetic correlations across eight distinct genomic regions. Specifically, the 5p15.33 region, harboring the TERT and CLPTM1L genes, showed statistically significant local genetic correlations for multiple cancer pairs. We conducted a cross-cancer fine-mapping of the 5p15.33 region based on eight cancers that showed genome-wide significant associations in this region (ER-negative breast, colorectal, glioma, lung, melanoma, ovarian, pancreatic, and prostate cancer). We used an iterative analysis pipeline implementing a subset-based meta-analysis approach based on cancer-specific conditional analyses and identified ten independent cross-cancer associations within this region. For each signal, we conducted cross-cancer fine-mapping to prioritize the most plausible causal variants. Our findings provide a more in-depth understanding of the shared inherited basis across human cancers and expand our knowledge of the 5p15.33 region in carcinogenesis.
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| 60. |
- Cuni-Sanchez, Aida, et al.
(författare)
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High aboveground carbon stock of African tropical montane forests
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 596:7873, s. 536-542
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Tidskriftsartikel (refereegranskat)abstract
- Tropical forests store 40–50 per cent of terrestrial vegetation carbon. However, spatial variations in aboveground live tree biomass carbon (AGC) stocks remain poorly understood, in particular in tropical montane forests. Owing to climatic and soil changes with increasing elevation, AGC stocks are lower in tropical montane forests compared with lowland forests. Here we assemble and analyse a dataset of structurally intact old-growth forests (AfriMont) spanning 44 montane sites in 12 African countries. We find that montane sites in the AfriMont plot network have a mean AGC stock of 149.4 megagrams of carbon per hectare (95% confidence interval 137.1–164.2), which is comparable to lowland forests in the African Tropical Rainforest Observation Network4 and about 70 per cent and 32 per cent higher than averages from plot networks in montane and lowland forests in the Neotropics, respectively. Notably, our results are two-thirds higher than the Intergovernmental Panel on Climate Change default values for these forests in Africa8. We find that the low stem density and high abundance of large trees of African lowland forests is mirrored in the montane forests sampled. This carbon store is endangered: we estimate that 0.8 million hectares of old-growth African montane forest have been lost since 2000. We provide country-specific montane forest AGC stock estimates modelled from our plot network to help to guide forest conservation and reforestation interventions. Our findings highlight the need for conserving these biodiverse and carbon-rich ecosystems.
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