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| 2. |
- Olive, M, et al.
(författare)
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Myoglobinopathy is an adult-onset autosomal dominant myopathy with characteristic sarcoplasmic inclusions
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 1396-
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Tidskriftsartikel (refereegranskat)abstract
- Myoglobin, encoded by MB, is a small cytoplasmic globular hemoprotein highly expressed in cardiac myocytes and oxidative skeletal myofibers. Myoglobin binds O2, facilitates its intracellular transport and serves as a controller of nitric oxide and reactive oxygen species. Here, we identify a recurrent c.292C>T (p.His98Tyr) substitution in MB in fourteen members of six European families suffering from an autosomal dominant progressive myopathy with highly characteristic sarcoplasmic inclusions in skeletal and cardiac muscle. Myoglobinopathy manifests in adulthood with proximal and axial weakness that progresses to involve distal muscles and causes respiratory and cardiac failure. Biochemical characterization reveals that the mutant myoglobin has altered O2 binding, exhibits a faster heme dissociation rate and has a lower reduction potential compared to wild-type myoglobin. Preliminary studies show that mutant myoglobin may result in elevated superoxide levels at the cellular level. These data define a recognizable muscle disease associated with MB mutation.
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| 4. |
- Heinze, Christoph, et al.
(författare)
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The ocean carbon sink – impacts, vulnerabilities, and challenges
- 2015
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Ingår i: Earth System Dynamics. - : Copernicus GmbH. - 2190-4979 .- 2190-4987. ; 6, s. 327-358
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Tidskriftsartikel (refereegranskat)abstract
- Carbon dioxide (CO 2 ) is, next to water vapour, considered to be the most important natural green- house gas on Earth. Rapidly rising atmospheric CO 2 concentrations caused by human actions such as fossil fuel burning, land-use change or cement production over the past 250 years have given cause for concern that changes in Earth’s climate system may progress at a much faster pace and larger extent than during the past 20 000 years. Investigating global carbon cycle pathways and finding suitable adaptation and mitigation strate- gies has, therefore, become of major concern in many research fields. The oceans have a key role in regulating atmospheric CO 2 concentrations and currently take up about 25 % of annual anthropogenic carbon emissions to the atmosphere. Questions that yet need to be answered are what the carbon uptake kinetics of the oceans will be in the future and how the increase in oceanic carbon inventory will affect its ecosystems and their services. This requires comprehensive investigations, including high-quality ocean carbon measurements on different spatial and temporal scales, the management of data in sophisticated databases, the application of Earth system models to provide future projections for given emission scenarios as well as a global synthesis and outreach to policy makers. In this paper, the current understanding of the ocean as an important carbon sink is reviewed with re- spect to these topics. Emphasis is placed on the complex interplay of different physical, chemical and biological processes that yield both positive and negative air–sea flux values for natural and anthropogenic CO 2 as well as on increased CO 2 (uptake) as the regulating force of the radiative warming of the atmosphere and the gradual acidification of the oceans. Major future ocean carbon challenges in the fields of ocean observations, modelling and process research as well as the relevance of other biogeochemical cycles and greenhouse gases are discussed
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| 6. |
- Madireddy, L, et al.
(författare)
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A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2236-
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified more than 50,000 unique associations with common human traits. While this represents a substantial step forward, establishing the biology underlying these associations has proven extremely difficult. Even determining which cell types and which particular gene(s) are relevant continues to be a challenge. Here, we conduct a cell-specific pathway analysis of the latest GWAS in multiple sclerosis (MS), which had analyzed a total of 47,351 cases and 68,284 healthy controls and found more than 200 non-MHC genome-wide associations. Our analysis identifies pan immune cell as well as cell-specific susceptibility genes in T cells, B cells and monocytes. Finally, genotype-level data from 2,370 patients and 412 controls is used to compute intra-individual and cell-specific susceptibility pathways that offer a biological interpretation of the individual genetic risk to MS. This approach could be adopted in any other complex trait for which genome-wide data is available.
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| 8. |
- Schwinger, J., et al.
(författare)
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Evaluation of NorESM-OC (versions 1 and 1.2), the ocean carbon-cycle stand-alone configuration of the Norwegian Earth System Model (NorESM1)
- 2016
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Ingår i: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X .- 1991-9603. ; 9:8, s. 2589-2622
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Tidskriftsartikel (refereegranskat)abstract
- Idealised and hindcast simulations performed with the stand-alone ocean carbon-cycle configuration of the Norwegian Earth System Model (NorESM-OC) are described and evaluated. We present simulation results of three different model configurations (two different model versions at different grid resolutions) using two different atmospheric forcing data sets. Model version NorESM-OC1 corresponds to the version that is included in the NorESM-ME1 fully coupled model, which participated in CMIP5. The main update between NorESM-OC1 and NorESM-OC1.2 is the addition of two new options for the treatment of sinking particles. We find that using a constant sinking speed, which has been the standard in NorESM's ocean carbon cycle module HAMOCC (HAMburg Ocean Carbon Cycle model), does not transport enough particulate organic carbon (POC) into the deep ocean below approximately 2000m depth. The two newly implemented parameterisations, a particle aggregation scheme with prognostic sinking speed, and a simpler scheme that uses a linear increase in the sinking speed with depth, provide better agreement with observed POC fluxes. Additionally, reduced deep ocean biases of oxygen and remineralised phosphate indicate a better performance of the new parameterisations. For model version 1.2, a re-tuning of the ecosystem parameterisation has been performed, which (i) reduces previously too high primary production at high latitudes, (ii) consequently improves model results for surface nutrients, and (iii) reduces alkalinity and dissolved inorganic carbon biases at low latitudes. We use hindcast simulations with prescribed observed and constant (pre-industrial) atmospheric CO2 concentrations to derive the past and contemporary ocean carbon sink. For the period 1990-1999 we find an average ocean carbon uptake ranging from 2.01 to 2.58PgCyr-1 depending on model version, grid resolution, and atmospheric forcing data set. © Author(s) 2016.
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| 9. |
- van Rheenen, Wouter, et al.
(författare)
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Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis
- 2016
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:9, s. 1043-1048
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Tidskriftsartikel (refereegranskat)abstract
- To elucidate the genetic architecture of amyotrophic lateral sclerosis (ALS) and find associated loci, we assembled a custom imputation reference panel from whole-genome-sequenced patients with ALS and matched controls (n = 1,861). Through imputation and mixed-model association analysis in 12,577 cases and 23,475 controls, combined with 2,579 cases and 2,767 controls in an independent replication cohort, we fine-mapped a new risk locus on chromosome 21 and identified C21orf2 as a gene associated with ALS risk. In addition, we identified MOBP and SCFD1 as new associated risk loci. We established evidence of ALS being a complex genetic trait with a polygenic architecture. Furthermore, we estimated the SNP-based heritability at 8.5%, with a distinct and important role for low-frequency variants (frequency 1-10%). This study motivates the interrogation of larger samples with full genome coverage to identify rare causal variants that underpin ALS risk.
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