| 1. |
- Bar, N., et al.
(författare)
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A reference map of potential determinants for the human serum metabolome
- 2020
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Ingår i: Nature. - : Nature Research. - 0028-0836 .- 1476-4687. ; 588:7836, s. 135-140
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Tidskriftsartikel (refereegranskat)abstract
- The serum metabolome contains a plethora of biomarkers and causative agents of various diseases, some of which are endogenously produced and some that have been taken up from the environment1. The origins of specific compounds are known, including metabolites that are highly heritable2,3, or those that are influenced by the gut microbiome4, by lifestyle choices such as smoking5, or by diet6. However, the key determinants of most metabolites are still poorly understood. Here we measured the levels of 1,251 metabolites in serum samples from a unique and deeply phenotyped healthy human cohort of 491 individuals. We applied machine-learning algorithms to predict metabolite levels in held-out individuals on the basis of host genetics, gut microbiome, clinical parameters, diet, lifestyle and anthropometric measurements, and obtained statistically significant predictions for more than 76% of the profiled metabolites. Diet and microbiome had the strongest predictive power, and each explained hundreds of metabolites—in some cases, explaining more than 50% of the observed variance. We further validated microbiome-related predictions by showing a high replication rate in two geographically independent cohorts7,8 that were not available to us when we trained the algorithms. We used feature attribution analysis9 to reveal specific dietary and bacterial interactions. We further demonstrate that some of these interactions might be causal, as some metabolites that we predicted to be positively associated with bread were found to increase after a randomized clinical trial of bread intervention. Overall, our results reveal potential determinants of more than 800 metabolites, paving the way towards a mechanistic understanding of alterations in metabolites under different conditions and to designing interventions for manipulating the levels of circulating metabolites.
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| 2. |
- Wilman, H. R., et al.
(författare)
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Genetic studies of abdominal MRI data identify genes regulating hepcidin as major determinants of liver iron concentration
- 2019
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Ingår i: Journal of Hepatology. - : Elsevier. - 0168-8278 .- 1600-0641. ; 71:3, s. 594-602
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Excess liver iron content is common and is linked to the risk of hepatic and extrahepatic diseases. We aimed to identify genetic variants influencing liver iron content and use genetics to understand its link to other traits and diseases. Methods: First, we performed a genome-wide association study (GWAS) in 8,289 individuals from UK Biobank, whose liver iron level had been quantified by magnetic resonance imaging, before validating our findings in an independent cohort (n = 1,513 from IMI DIRECT). Second, we used Mendelian randomisation to test the causal effects of 25 predominantly metabolic traits on liver iron content. Third, we tested phenome-wide associations between liver iron variants and 770 traits and disease outcomes. Results: We identified 3 independent genetic variants (rs1800562 [C282Y] and rs1799945 [H63D] in HFE and rs855791 [V736A] in TMPRSS6) associated with liver iron content that reached the GWAS significance threshold (p <5 × 10−8). The 2 HFE variants account for ∼85% of all cases of hereditary haemochromatosis. Mendelian randomisation analysis provided evidence that higher central obesity plays a causal role in increased liver iron content. Phenome-wide association analysis demonstrated shared aetiopathogenic mechanisms for elevated liver iron, high blood pressure, cirrhosis, malignancies, neuropsychiatric and rheumatological conditions, while also highlighting inverse associations with anaemias, lipidaemias and ischaemic heart disease. Conclusion: Our study provides genetic evidence that mechanisms underlying higher liver iron content are likely systemic rather than organ specific, that higher central obesity is causally associated with higher liver iron, and that liver iron shares common aetiology with multiple metabolic and non-metabolic diseases. Lay summary: Excess liver iron content is common and is associated with liver diseases and metabolic diseases including diabetes, high blood pressure, and heart disease. We identified 3 genetic variants that are linked to an increased risk of developing higher liver iron content. We show that the same genetic variants are linked to higher risk of many diseases, but they may also be associated with some health advantages. Finally, we use genetic variants associated with waist-to-hip ratio as a tool to show that central obesity is causally associated with increased liver iron content.
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| 3. |
- Allesøe, Rosa Lundbye, et al.
(författare)
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Discovery of drug–omics associations in type 2 diabetes with generative deep-learning models
- 2023
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Ingår i: Nature Biotechnology. - : Springer Nature. - 1087-0156 .- 1546-1696. ; 41:3, s. 399-408
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Tidskriftsartikel (refereegranskat)abstract
- The application of multiple omics technologies in biomedical cohorts has the potential to reveal patient-level disease characteristics and individualized response to treatment. However, the scale and heterogeneous nature of multi-modal data makes integration and inference a non-trivial task. We developed a deep-learning-based framework, multi-omics variational autoencoders (MOVE), to integrate such data and applied it to a cohort of 789 people with newly diagnosed type 2 diabetes with deep multi-omics phenotyping from the DIRECT consortium. Using in silico perturbations, we identified drug–omics associations across the multi-modal datasets for the 20 most prevalent drugs given to people with type 2 diabetes with substantially higher sensitivity than univariate statistical tests. From these, we among others, identified novel associations between metformin and the gut microbiota as well as opposite molecular responses for the two statins, simvastatin and atorvastatin. We used the associations to quantify drug–drug similarities, assess the degree of polypharmacy and conclude that drug effects are distributed across the multi-omics modalities.
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| 4. |
- Brown, A.A., et al.
(författare)
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Genetic analysis of blood molecular phenotypes reveals common properties in the regulatory networks affecting complex traits
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- We evaluate the shared genetic regulation of mRNA molecules, proteins and metabolites derived from whole blood from 3029 human donors. We find abundant allelic heterogeneity, where multiple variants regulate a particular molecular phenotype, and pleiotropy, where a single variant associates with multiple molecular phenotypes over multiple genomic regions. The highest proportion of share genetic regulation is detected between gene expression and proteins (66.6%), with a further median shared genetic associations across 49 different tissues of 78.3% and 62.4% between plasma proteins and gene expression. We represent the genetic and molecular associations in networks including 2828 known GWAS variants, showing that GWAS variants are more often connected to gene expression in trans than other molecular phenotypes in the network. Our work provides a roadmap to understanding molecular networks and deriving the underlying mechanism of action of GWAS variants using different molecular phenotypes in an accessible tissue. © 2023, Springer Nature Limited.
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| 8. |
- Vegelius, J. R., et al.
(författare)
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Cu K beta(2,5) X-ray emission spectroscopy as a tool for characterization of monovalent copper compounds
- 2012
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Ingår i: Journal of Analytical Atomic Spectrometry. - : Royal Society of Chemistry (RSC). - 0267-9477 .- 1364-5544. ; 27:11, s. 1882-1888
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Tidskriftsartikel (refereegranskat)abstract
- Cu Kβ 2,5 X-ray emission and resonant inelastic X-ray scattering measurements were performed on monovalent and divalent copper compounds. The data were compared with the results of local-density- approximation calculations. The methods were found to be efficient tools for studies of Cu 4p states in the valence band and for distinguishing between different monovalent copper compounds. This is of particular importance for the debate concerning copper corrosion in oxygen-free water.
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| 14. |
- Butorin, Sergei, et al.
(författare)
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Effect of Ag Doping on Electronic Structure of Cluster Compounds AgxMo9Se11 (x = 3.4, 3.9)
- 2018
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Ingår i: ACS Applied Energy Materials. - : American Chemical Society (ACS). - 2574-0962. ; 1:8, s. 4032-4039
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Tidskriftsartikel (refereegranskat)abstract
- The electronic structure of AgxMo9Se11 as a potential material for thermoelectric applications was studied using high-energy-resolution fluorescence-detection X-ray absorption spectroscopy (HERFD-XAS) and the resonant inelastic X-ray scattering (RIXS) technique. The experiments were supported by first-principle calculations using density functional theory (DFT). The analysis of obtained spectra indicate the presence of subvalent (less than 1+) Ag in AgxMo9Se11. The advanced HERFD-XAS measurements allowed us to resolve the contribution of the electronic states at the Fermi level of AgxMo9Se11 and to monitor its dependence on the x value. A comparison of the experimental data with the results of the DFT calculations suggests the importance of the Ag2-type sites with the shortest Ag–Se distance for affecting the properties of AgxMo9Se11.
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| 15. |
- Derenzo, S. E., et al.
(författare)
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Scintillation studies of CdS(In): effects of various semiconductor doping strategies
- 2005
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002. ; 537:1-2, s. 261-
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Tidskriftsartikel (refereegranskat)abstract
- We present room-temperature photoluminescence and pulsed X-ray measurements of powder samples of CdS(In) codoped with three hole traps (Te, Ag, and Na). Te is an isoelectronic hole trap and Ag, and Na are acceptor hole traps. The emission of CdS(In) excited at 430 nm is centered at approximate to 520 nm (near the band edge) with approximate to 20 nm FWHM. The emissions from CdS(Te) and the three codoped samples are shifted to longer wavelengths and are characterized by broad emission bands peaking near 630 nm. Whereas the decay of the CdS(Te) emission is nonexponential with times > 10 its, the decay of CdS(In, Te) is 3.3 ns and exponential over three decades. The decay of the acceptor-doped samples CdS(In,Ag) and CdS(In, Na) are also fast, 2.5 and 2.8 ns, respectively. These results show the potential for developing fast inorganic scintillators based on direct-gap semiconductors that can be codoped to provide fast radiative recombination. Additional work is needed to increase the luminosity.
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| 16. |
- Ekman, M J, et al.
(författare)
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6-minute walk test before and after a weight reduction program in obese subjects.
- 2013
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Ingår i: Obesity. - : Wiley. - 1930-739X .- 1930-7381. ; 21:3, s. 236-243
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Tidskriftsartikel (refereegranskat)abstract
- Weight loss and physical activity have shown favorable effects on risks associated with obesity. It is therefore of interest to evaluate exercise capacity and related co-morbidities in obese patients. We present data from obese subjects evaluated by the 6-minute walk test (6MWT) before and after a 7.3 (6.1-8.2) month weight reduction program. 251 subjects completed the test at baseline (BMI 40.6 [36.9-44.6] kg/m(2) ) and 129 (51.4 %) repeated the test after intervention (BMI 35.6 [31.2-38.5] kg/m(2) ). The six minute walking distance (6MWD) at baseline (535 [480-580] m) and at follow up (599 [522-640] m) correlated to several cardiovascular risk markers. Age, weight, height, resting heart rate, smoking status, fP-glucose and use of ß-blockers explained 43 % of the variance in predicted 6MWD at baseline. The effect of smoking status, fP-glucose, ß-blockers and resting heart rate lost significance at follow up. Presence of diabetes and the metabolic syndrome had a negative influence on 6MWD but did not affect the impact of intervention based on percentage increase in walking distance. Gender had no impact on 6MWD. Reported pain during the test was common but decreased after intervention (57.0 % vs. 28.7 %, p<0.001). In conclusion, the 6MWT may be used to evaluate intervention success beyond kilogram weight loss in obese subjects. We present formulas to predict 6MWD and the effect of weight loss on walking distance in clinical practice. Pain is a common problem which has to be considered when giving advice on exercise as a part of weight loss intervention.
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| 22. |
- Klintenberg, M, et al.
(författare)
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Calculation of energy levels and polarized oscillator strengths for Nd3+:YAG
- 1997
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Ingår i: PHYSICAL REVIEW B-CONDENSED MATTER. - : AMER INST PHYSICS. - 0163-1829. ; 55:16, s. 10369-10375
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The effect of an electrostatic crystal-field (CF) model on energy levels and oscillator strengths for Nd3+:YAG (where YAG denotes yttrium aluminum garnet) has been studied. Three-parameters for the correction of the Slater integrals F-2, F-4, and F-6 and
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| 23. |
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| 24. |
- Klintenberg, Mattias, et al.
(författare)
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Theoretical analysis of the chemical bonding and electronic structure of graphene interacting with Group IA and Group VIIA elements
- 2010
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 81:8, s. 085433-
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Tidskriftsartikel (refereegranskat)abstract
- We propose a different class of materials, which can be viewed as graphene derivatives involving Group IA or Group VIIA elements, forming what we refer to as graphXene. We show that in several cases, large band gaps can be found to open up whereas in other cases, a semimetallic behavior is found. Formation energies indicate that under ambient conditions, sp(3) and mixed sp(2)/sp(3) systems will form. The results presented allow us to propose that by careful tuning of the relative concentration of the adsorbed atoms, it should be possible to tune the band gap of graphXene to take any value between 0 and 6.4 eV.
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| 25. |
- Klintenberg, Patrik, et al.
(författare)
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Assessing biogas potential of slaughter waste : Can biogas production solve a serious waste problem at abattoirs?
- 2014
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Ingår i: Energy Procedia. - : Elsevier BV. - 1876-6102. ; 61, s. 2600-2603
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Tidskriftsartikel (refereegranskat)abstract
- Management of solid waste and wastewater in Namibia is a growing concern. This study investigated the biogas potential of slaughter waste at a small stock abattoir in southern Namibia. Laboratory experiments with five different mixes of blood; stomach content and manure from sheep were tested. Preliminary findings suggest that the most optimum mixture of slaughter waste was relatively large amounts of stomach and intestine content. The blood proportion should be kept relatively low, since the high nitrogen contents in the blood may inhibit the biogas production. The substrate mixture reflecting the actual ratio of waste generated in the slaughter process resulted in the highest methane production. This suggests that it is possible to produce viable amounts of biogas only using the waste produced at the abattoir, without adding other green substrate. Findings presented here together with results from a larger biogas digester, will be elaborated in the full paper.
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