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- Bousquet, J, et al.
(författare)
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Nrf2-interacting nutrients and COVID-19: time for research to develop adaptation strategies
- 2020
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Ingår i: Clinical and translational allergy. - : Wiley. - 2045-7022. ; 10:1, s. 58-
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Tidskriftsartikel (refereegranskat)abstract
- There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPARγ:Peroxisome proliferator-activated receptor, NFκB: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2α:Elongation initiation factor 2α). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT1R axis (AT1R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity.
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- Taddei, C, et al.
(författare)
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Repositioning of the global epicentre of non-optimal cholesterol
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 582:7810, s. 73-
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Tidskriftsartikel (refereegranskat)abstract
- High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol—which is a marker of cardiovascular risk—changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million–4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.
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- Aghanim, N., et al.
(författare)
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Planck 2018 results I. Overview and the cosmological legacy of Planck
- 2020
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 641
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Tidskriftsartikel (refereegranskat)abstract
- The European Space Agency's Planck satellite, which was dedicated to studying the early Universe and its subsequent evolution, was launched on 14 May 2009. It scanned the microwave and submillimetre sky continuously between 12 August 2009 and 23 October 2013, producing deep, high-resolution, all-sky maps in nine frequency bands from 30 to 857 GHz. This paper presents the cosmological legacy of Planck, which currently provides our strongest constraints on the parameters of the standard cosmological model and some of the tightest limits available on deviations from that model. The 6-parameter Lambda CDM model continues to provide an excellent fit to the cosmic microwave background data at high and low redshift, describing the cosmological information in over a billion map pixels with just six parameters. With 18 peaks in the temperature and polarization angular power spectra constrained well, Planck measures five of the six parameters to better than 1% (simultaneously), with the best-determined parameter (theta (*)) now known to 0.03%. We describe the multi-component sky as seen by Planck, the success of the Lambda CDM model, and the connection to lower-redshift probes of structure formation. We also give a comprehensive summary of the major changes introduced in this 2018 release. The Planck data, alone and in combination with other probes, provide stringent constraints on our models of the early Universe and the large-scale structure within which all astrophysical objects form and evolve. We discuss some lessons learned from the Planck mission, and highlight areas ripe for further experimental advances.
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| 7. |
- Bryois, J., et al.
(författare)
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Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson’s disease
- 2020
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 52:5, s. 482-493
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have discovered hundreds of loci associated with complex brain disorders, but it remains unclear in which cell types these loci are active. Here we integrate genome-wide association study results with single-cell transcriptomic data from the entire mouse nervous system to systematically identify cell types underlying brain complex traits. We show that psychiatric disorders are predominantly associated with projecting excitatory and inhibitory neurons. Neurological diseases were associated with different cell types, which is consistent with other lines of evidence. Notably, Parkinson’s disease was genetically associated not only with cholinergic and monoaminergic neurons (which include dopaminergic neurons) but also with enteric neurons and oligodendrocytes. Using post-mortem brain transcriptomic data, we confirmed alterations in these cells, even at the earliest stages of disease progression. Our study provides an important framework for understanding the cellular basis of complex brain maladies, and reveals an unexpected role of oligodendrocytes in Parkinson’s disease. © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
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| 8. |
- Aghanim, N., et al.
(författare)
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Planck 2018 results V. CMB power spectra and likelihoods
- 2020
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 641
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Tidskriftsartikel (refereegranskat)abstract
- We describe the legacy Planck cosmic microwave background (CMB) likelihoods derived from the 2018 data release. The overall approach is similar in spirit to the one retained for the 2013 and 2015 data release, with a hybrid method using different approximations at low (l< 30) and high (l >= 30) multipoles, implementing several methodological and data-analysis refinements compared to previous releases. With more realistic simulations, and better correction and modelling of systematic effects, we can now make full use of the CMB polarization observed in the High Frequency Instrument (HFI) channels. The low-multipole EE cross-spectra from the 100 GHz and 143 GHz data give a constraint on the Lambda CDM reionization optical-depth parameter tau to better than 15% (in combination with the TT low-l data and the high-l temperature and polarization data), tightening constraints on all parameters with posterior distributions correlated with tau. We also update the weaker constraint on tau from the joint TEB likelihood using the Low Frequency Instrument (LFI) channels, which was used in 2015 as part of our baseline analysis. At higher multipoles, the CMB temperature spectrum and likelihood are very similar to previous releases. A better model of the temperature-to-polarization leakage and corrections for the effective calibrations of the polarization channels (i.e., the polarization efficiencies) allow us to make full use of polarization spectra, improving the Lambda CDM constraints on the parameters theta(MC), omega(c), omega(b), and H-0 by more than 30%, and n(s) by more than 20% compared to TT-only constraints. Extensive tests on the robustness of the modelling of the polarization data demonstrate good consistency, with some residual modelling uncertainties. At high multipoles, we are now limited mainly by the accuracy of the polarization efficiency modelling. Using our various tests, simulations, and comparison between different high-multipole likelihood implementations, we estimate the consistency of the results to be better than the 0.5 sigma level on the Lambda CDM parameters, as well as classical single-parameter extensions for the joint likelihood (to be compared to the 0.3 sigma levels we achieved in 2015 for the temperature data alone on Lambda CDM only). Minor curiosities already present in the previous releases remain, such as the differences between the best-fit Lambda CDM parameters for the l< 800 and l> 800 ranges of the power spectrum, or the preference for more smoothing of the power-spectrum peaks than predicted in Lambda CDM fits. These are shown to be driven by the temperature power spectrum and are not significantly modified by the inclusion of the polarization data. Overall, the legacy Planck CMB likelihoods provide a robust tool for constraining the cosmological model and represent a reference for future CMB observations.
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| 9. |
- Aghanim, N., et al.
(författare)
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Planck 2018 results VI. Cosmological parameters
- 2020
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 641
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Tidskriftsartikel (refereegranskat)abstract
- We present cosmological parameter results from the final full-mission Planck measurements of the cosmic microwave background (CMB) anisotropies, combining information from the temperature and polarization maps and the lensing reconstruction. Compared to the 2015 results, improved measurements of large-scale polarization allow the reionization optical depth to be measured with higher precision, leading to significant gains in the precision of other correlated parameters. Improved modelling of the small-scale polarization leads to more robust constraints on many parameters, with residual modelling uncertainties estimated to affect them only at the 0.5 sigma level. We find good consistency with the standard spatially-flat 6-parameter Lambda CDM cosmology having a power-law spectrum of adiabatic scalar perturbations (denoted base Lambda CDM in this paper), from polarization, temperature, and lensing, separately and in combination. A combined analysis gives dark matter density Omega (c)h(2)=0.120 +/- 0.001, baryon density Omega (b)h(2)=0.0224 +/- 0.0001, scalar spectral index n(s)=0.965 +/- 0.004, and optical depth tau =0.054 +/- 0.007 (in this abstract we quote 68% confidence regions on measured parameters and 95% on upper limits). The angular acoustic scale is measured to 0.03% precision, with 100 theta (*)=1.0411 +/- 0.0003. These results are only weakly dependent on the cosmological model and remain stable, with somewhat increased errors, in many commonly considered extensions. Assuming the base-Lambda CDM cosmology, the inferred (model-dependent) late-Universe parameters are: Hubble constant H-0=(67.4 +/- 0.5) km s(-1) Mpc(-1); matter density parameter Omega (m)=0.315 +/- 0.007; and matter fluctuation amplitude sigma (8)=0.811 +/- 0.006. We find no compelling evidence for extensions to the base-Lambda CDM model. Combining with baryon acoustic oscillation (BAO) measurements (and considering single-parameter extensions) we constrain the effective extra relativistic degrees of freedom to be N-eff=2.99 +/- 0.17, in agreement with the Standard Model prediction N-eff=3.046, and find that the neutrino mass is tightly constrained to Sigma m(nu)< 0.12 eV. The CMB spectra continue to prefer higher lensing amplitudes than predicted in base CDM at over 2 sigma, which pulls some parameters that affect the lensing amplitude away from the Lambda CDM model; however, this is not supported by the lensing reconstruction or (in models that also change the background geometry) BAO data. The joint constraint with BAO measurements on spatial curvature is consistent with a flat universe, Omega (K)=0.001 +/- 0.002. Also combining with Type Ia supernovae (SNe), the dark-energy equation of state parameter is measured to be w(0)=-1.03 +/- 0.03, consistent with a cosmological constant. We find no evidence for deviations from a purely power-law primordial spectrum, and combining with data from BAO, BICEP2, and Keck Array data, we place a limit on the tensor-to-scalar ratio r(0.002)< 0.06. Standard big-bang nucleosynthesis predictions for the helium and deuterium abundances for the base-CDM cosmology are in excellent agreement with observations. The Planck base-Lambda CDM results are in good agreement with BAO, SNe, and some galaxy lensing observations, but in slight tension with the Dark Energy Survey's combined-probe results including galaxy clustering (which prefers lower fluctuation amplitudes or matter density parameters), and in significant, 3.6 sigma, tension with local measurements of the Hubble constant (which prefer a higher value). Simple model extensions that can partially resolve these tensions are not favoured by the Planck data.
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| 10. |
- Aghanim, N., et al.
(författare)
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Planck 2018 results XII. Galactic astrophysics using polarized dust emission
- 2020
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 641
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Tidskriftsartikel (refereegranskat)abstract
- Observations of the submillimetre emission from Galactic dust, in both total intensity I and polarization, have received tremendous interest thanks to the Planck full-sky maps. In this paper we make use of such full-sky maps of dust polarized emission produced from the third public release of Planck data. As the basis for expanding on astrophysical studies of the polarized thermal emission from Galactic dust, we present full-sky maps of the dust polarization fraction p, polarization angle psi, and dispersion function of polarization angles ?. The joint distribution (one-point statistics) of p and N-H confirms that the mean and maximum polarization fractions decrease with increasing N-H. The uncertainty on the maximum observed polarization fraction, (max) = 22.0(-1.4)(+3.5) p max = 22 . 0 - 1.4 + 3.5 % at 353 GHz and 80 ' resolution, is dominated by the uncertainty on the Galactic emission zero level in total intensity, in particular towards diffuse lines of sight at high Galactic latitudes. Furthermore, the inverse behaviour between p and ? found earlier is seen to be present at high latitudes. This follows the ?proportional to p(-1) relationship expected from models of the polarized sky (including numerical simulations of magnetohydrodynamical turbulence) that include effects from only the topology of the turbulent magnetic field, but otherwise have uniform alignment and dust properties. Thus, the statistical properties of p, psi, and ? for the most part reflect the structure of the Galactic magnetic field. Nevertheless, we search for potential signatures of varying grain alignment and dust properties. First, we analyse the product map ?xp, looking for residual trends. While the polarization fraction p decreases by a factor of 3-4 between N-H=10(20) cm(-2) and N-H=2x10(22) cm(-2), out of the Galactic plane, this product ?xp only decreases by about 25%. Because ? is independent of the grain alignment efficiency, this demonstrates that the systematic decrease in p with N-H is determined mostly by the magnetic-field structure and not by a drop in grain alignment. This systematic trend is observed both in the diffuse interstellar medium (ISM) and in molecular clouds of the Gould Belt. Second, we look for a dependence of polarization properties on the dust temperature, as we would expect from the radiative alignment torque (RAT) theory. We find no systematic trend of ?xp with the dust temperature T-d, whether in the diffuse ISM or in the molecular clouds of the Gould Belt. In the diffuse ISM, lines of sight with high polarization fraction p and low polarization angle dispersion ? tend, on the contrary, to have colder dust than lines of sight with low p and high ?. We also compare the Planck thermal dust polarization with starlight polarization data in the visible at high Galactic latitudes. The agreement in polarization angles is remarkable, and is consistent with what we expect from the noise and the observed dispersion of polarization angles in the visible on the scale of the Planck beam. The two polarization emission-to-extinction ratios, R-P/p and R-S/V, which primarily characterize dust optical properties, have only a weak dependence on the column density, and converge towards the values previously determined for translucent lines of sight. We also determine an upper limit for the polarization fraction in extinction, p(V)/E(B-V), of 13% at high Galactic latitude, compatible with the polarization fraction p approximate to 20% observed at 353 GHz. Taken together, these results provide strong constraints for models of Galactic dust in diffuse gas.
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