| 1. |
- Fromentin, S., et al.
(författare)
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Microbiome and metabolome features of the cardiometabolic disease spectrum
- 2022
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 28:2, s. 303-314
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Tidskriftsartikel (refereegranskat)abstract
- By studying individuals along a spectrum of cardiometabolic disease and adjusting for effects of lifestyle and medication, this investigation identifies alterations of the metabolome and microbiome from dysmetabolic conditions, such as obesity and type 2 diabetes, to ischemic heart disease. Previous microbiome and metabolome analyses exploring non-communicable diseases have paid scant attention to major confounders of study outcomes, such as common, pre-morbid and co-morbid conditions, or polypharmacy. Here, in the context of ischemic heart disease (IHD), we used a study design that recapitulates disease initiation, escalation and response to treatment over time, mirroring a longitudinal study that would otherwise be difficult to perform given the protracted nature of IHD pathogenesis. We recruited 1,241 middle-aged Europeans, including healthy individuals, individuals with dysmetabolic morbidities (obesity and type 2 diabetes) but lacking overt IHD diagnosis and individuals with IHD at three distinct clinical stages-acute coronary syndrome, chronic IHD and IHD with heart failure-and characterized their phenome, gut metagenome and serum and urine metabolome. We found that about 75% of microbiome and metabolome features that distinguish individuals with IHD from healthy individuals after adjustment for effects of medication and lifestyle are present in individuals exhibiting dysmetabolism, suggesting that major alterations of the gut microbiome and metabolome might begin long before clinical onset of IHD. We further categorized microbiome and metabolome signatures related to prodromal dysmetabolism, specific to IHD in general or to each of its three subtypes or related to escalation or de-escalation of IHD. Discriminant analysis based on specific IHD microbiome and metabolome features could better differentiate individuals with IHD from healthy individuals or metabolically matched individuals as compared to the conventional risk markers, pointing to a pathophysiological relevance of these features.
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| 2. |
- Forslund, Sofia K., et al.
(författare)
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Combinatorial, additive and dose-dependent drug–microbiome associations
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 600:7889, s. 500-505
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Tidskriftsartikel (refereegranskat)abstract
- During the transition from a healthy state to cardiometabolic disease, patients become heavily medicated, which leads to an increasingly aberrant gut microbiome and serum metabolome, and complicates biomarker discovery1–5. Here, through integrated multi-omics analyses of 2,173 European residents from the MetaCardis cohort, we show that the explanatory power of drugs for the variability in both host and gut microbiome features exceeds that of disease. We quantify inferred effects of single medications, their combinations as well as additive effects, and show that the latter shift the metabolome and microbiome towards a healthier state, exemplified in synergistic reduction in serum atherogenic lipoproteins by statins combined with aspirin, or enrichment of intestinal Roseburia by diuretic agents combined with beta-blockers. Several antibiotics exhibit a quantitative relationship between the number of courses prescribed and progression towards a microbiome state that is associated with the severity of cardiometabolic disease. We also report a relationship between cardiometabolic drug dosage, improvement in clinical markers and microbiome composition, supporting direct drug effects. Taken together, our computational framework and resulting resources enable the disentanglement of the effects of drugs and disease on host and microbiome features in multimedicated individuals. Furthermore, the robust signatures identified using our framework provide new hypotheses for drug–host–microbiome interactions in cardiometabolic disease.
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| 3. |
- Thomas, H. J. D., et al.
(författare)
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Global plant trait relationships extend to the climatic extremes of the tundra biome
- 2020
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- The majority of variation in six traits critical to the growth, survival and reproduction of plant species is thought to be organised along just two dimensions, corresponding to strategies of plant size and resource acquisition. However, it is unknown whether global plant trait relationships extend to climatic extremes, and if these interspecific relationships are confounded by trait variation within species. We test whether trait relationships extend to the cold extremes of life on Earth using the largest database of tundra plant traits yet compiled. We show that tundra plants demonstrate remarkably similar resource economic traits, but not size traits, compared to global distributions, and exhibit the same two dimensions of trait variation. Three quarters of trait variation occurs among species, mirroring global estimates of interspecific trait variation. Plant trait relationships are thus generalizable to the edge of global trait-space, informing prediction of plant community change in a warming world.
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| 4. |
- Barausse, Enrico, et al.
(författare)
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Prospects for fundamental physics with LISA
- 2020
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Ingår i: General Relativity and Gravitation. - : SPRINGER/PLENUM PUBLISHERS. - 0001-7701 .- 1572-9532. ; 52:8
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In this paper, which is of programmatic rather than quantitative nature, we aim to further delineate and sharpen the future potential of the LISA mission in the area of fundamental physics. Given the very broad range of topics that might be relevant to LISA,we present here a sample of what we view as particularly promising fundamental physics directions. We organize these directions through a "science-first" approach that allows us to classify how LISA data can inform theoretical physics in a variety of areas. For each of these theoretical physics classes, we identify the sources that are currently expected to provide the principal contribution to our knowledge, and the areas that need further development. The classification presented here should not be thought of as cast in stone, but rather as a fluid framework that is amenable to change with the flow of new insights in theoretical physics.
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| 5. |
- Hawthorn, F., et al.
(författare)
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TOI-836: A super-Earth and mini-Neptune transiting a nearby K-dwarf
- 2023
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Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 520:3, s. 3649-3668
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Tidskriftsartikel (refereegranskat)abstract
- We present the discovery of two exoplanets transiting TOI-836 (TIC 440887364) using data from TESS Sector 11 and Sector 38. TOI-836 is a bright (T = 8.5 mag), high proper motion (∼200 mas yr−1), low metallicity ([Fe/H]≈−0.28) K-dwarf with a mass of 0.68 ± 0.05 M and a radius of 0.67 ± 0.01 R. We obtain photometric follow-up observations with a variety of facilities, and we use these data sets to determine that the inner planet, TOI-836 b, is a 1.70 ± 0.07 R super-Earth in a 3.82-d orbit, placing it directly within the so-called ‘radius valley’. The outer planet, TOI-836 c, is a 2.59 ± 0.09 R mini-Neptune in an 8.60-d orbit. Radial velocity measurements reveal that TOI-836 b has a mass of 4.5 ± 0.9 M, while TOI-836 c has a mass of 9.6 ± 2.6 M. Photometric observations show Transit Timing Variations (TTVs) on the order of 20 min for TOI-836 c, although there are no detectable TTVs for TOI-836 b. The TTVs of planet TOI-836 c may be caused by an undetected exterior planet.
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| 6. |
- Hoyer, S., et al.
(författare)
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TOI-220b: a warm sub-Neptune discovered by TESS
- 2021
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Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 505:3, s. 3361-3379
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, we report the discovery of TOI-220b, a new sub-Neptune detected by the Transiting Exoplanet Survey Satellite (TESS) and confirmed by radial velocity follow-up observations with the HARPS spectrograph. Based on the combined analysis of TESS transit photometry and high precision radial velocity measurements, we estimate a planetary mass of 13.8 +/- 1.0M(circle plus) and radius of 3.03 +/- 0.15R(circle plus), implying a bulk density of 2.73 +/- 0.47. TOI-220b orbits a relative bright (V=10.4) and old (10.1 +/- 1.4Gyr) K dwarf star with a period of similar to 10.69d. Thus, TOI-220b is a new warm sub-Neptune with very precise mass and radius determinations. A Bayesian analysis of the TOI-220b internal structure indicates that due to the strong irradiation it receives, the low density of this planet could be explained with a steam atmosphere in radiative-convective equilibrium and a supercritical water layer on top of a differentiated interior made of a silicate mantle and a small iron core.
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| 7. |
- Kjær, C., et al.
(författare)
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Gas-phase Förster resonance energy transfer in mass-selected ions with methylene or peptide linkers between two dyes: a concerted dance of charges
- 2020
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Ingår i: Physical chemistry chemical physics : PCCP. - : Royal Society of Chemistry (RSC). - 1463-9084 .- 1463-9076. ; 22:19, s. 11095-11100
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Tidskriftsartikel (refereegranskat)abstract
- Förster Resonance Energy Transfer (FRET) between a photoexcited and a ground-state dye is dictated by how far apart the two dyes are compared to the Förster distance. While there is a significant number of studies on the process for biomacromolecules in solution, there are only a few reports on gas-phase FRET. Here we report on a simple gas-phase model system, synthesized with the rhodamine 575 (R575+) and rhodamine 640 (R640+) FRET pair and a covalent linker with four methylenes, R575+-(CH2)4-R640+. Each dye carries a positive charge which allows for mass-spectroscopy experiments. We have recorded gas-phase dispersed fluorescence spectra of the mass-selected dications excited at different wavelengths using the homebuilt LUNA (LUminescence iNstrument in Aarhus) setup and find in all cases that emission is exclusively from the R640+ acceptor dye. The linker does not interfere electronically with the dyes and simply acts as a spacer. We can therefore establish the direct effect of the interaction between the two dyes when it comes to emission band maximum. Indeed, we find that R640+ experiences a significant shift in its maximum from 560 ± 1 nm for the monomer cation to 577 ± 2 nm in the presence of R575+, independent of initial excitation of R575+ or R640+. This redshift is ascribed to the large polarizability along the long axis of the xanthene core structure, and that this polarizability is larger in the excited state than in the ground state. Experiments were also done on a triply charged 11-mer peptide labelled with the same two dyes, R575+-(Gly-Gln)5-Lys-R640+ + H+ (Gly = glycine, Gln = glutamine, and Lys = lysine) where the extra positive charge is located on the peptide. Again a redshifted emission spectrum of the donor is observed with maximum at 582 ± 2 nm. Our work clearly demonstrates strong sensitivity of the photophysics of one dye to the nearby environment, and that caution is needed when using the energy transfer efficiency to infer dye-dye separations in gas-phase experiments.
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| 8. |
- Lillo-Box, J., et al.
(författare)
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TOI-969: a late-K dwarf with a hot mini-Neptune in the desert and an eccentric cold Jupiter
- 2023
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 669
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Tidskriftsartikel (refereegranskat)abstract
- Context. The current architecture of a given multi-planetary system is a key fingerprint of its past formation and dynamical evolution history. Long-term follow-up observations are key to complete their picture. Aims. In this paper, we focus on the confirmation and characterization of the components of the TOI-969 planetary system, where TESS detected a Neptune-size planet candidate in a very close-in orbit around a late K-dwarf star. Methods. We use a set of precise radial velocity observations from HARPS, PFS, and CORALIE instruments covering more than two years in combination with the TESS photometric light curve and other ground-based follow-up observations to confirm and characterize the components of this planetary system. Results. We find that TOI-969 b is a transiting close-in (Pb ∼ 1.82 days) mini-Neptune planet (Formula Presented), placing it on the lower boundary of the hot-Neptune desert (Teq,b = 941 ± 31 K). The analysis of its internal structure shows that TOI-969 b is a volatile-rich planet, suggesting it underwent an inward migration. The radial velocity model also favors the presence of a second massive body in the system, TOI-969 c, with a long period of (Formula Presented) days, a minimum mass of (Formula Presented), and a highly eccentric orbit of (Formula Presented). Conclusions. The TOI-969 planetary system is one of the few around K-dwarfs known to have this extended configuration going from a very close-in planet to a wide-separation gaseous giant. TOI-969 b has a transmission spectroscopy metric of 93 and orbits a moderately bright (G = 11.3 mag) star, making it an excellent target for atmospheric studies. The architecture of this planetary system can also provide valuable information about migration and formation of planetary systems.
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| 9. |
- Osborn, A., et al.
(författare)
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TOI-332 b: a super dense Neptune found deep within the Neptunian desert
- 2023
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Ingår i: Monthly Notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 526:1, s. 548-566
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Tidskriftsartikel (refereegranskat)abstract
- To date, thousands of planets have been discovered, but there are regions of the orbital parameter space that are still bare. An example is the short period and intermediate mass/radius space known as the 'Neptunian desert', where planets should be easy to find but discoveries remain few. This suggests unusual formation and evolution processes are responsible for the planets residing here. We present the discovery of TOI-332 b, a planet with an ultra-short period of 0.78 d that sits firmly within the desert. It orbits a K0 dwarf with an effective temperature of 5251 ± 71 K. TOI-332 b has a radius of R, smaller than that of Neptune, but an unusually large mass of 57.2 ± 1.6 M. It has one of the highest densities of any Neptune-sized planet discovered thus far at g cm-3. A 4-layer internal structure model indicates it likely has a negligible hydrogen-helium envelope, something only found for a small handful of planets this massive, and so TOI-332 b presents an interesting challenge to planetary formation theories. We find that photoevaporation cannot account for the mass-loss required to strip this planet of the Jupiter-like envelope it would have been expected to accrete. We need to look towards other scenarios, such as high-eccentricity migration, giant impacts, or gap opening in the protoplanetary disc, to try and explain this unusual discovery.
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| 10. |
- Saevarsdottir, S., et al.
(författare)
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Multiomics analysis of rheumatoid arthritis yields sequence variants that have large effects on risk of the seropositive subset
- 2022
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 81:8
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To find causal genes for rheumatoid arthritis (RA) and its seropositive (RF and/or ACPA positive) and seronegative subsets. Methods We performed a genome-wide association study (GWAS) of 31 313 RA cases (68% seropositive) and similar to 1 million controls from Northwestern Europe. We searched for causal genes outside the HLA-locus through effect on coding, mRNA expression in several tissues and/or levels of plasma proteins (SomaScan) and did network analysis (Qiagen). Results We found 25 sequence variants for RA overall, 33 for seropositive and 2 for seronegative RA, altogether 37 sequence variants at 34 non-HLA loci, of which 15 are novel. Genomic, transcriptomic and proteomic analysis of these yielded 25 causal genes in seropositive RA and additional two overall. Most encode proteins in the network of interferon-alpha/beta and IL-12/23 that signal through the JAK/STAT-pathway. Highlighting those with largest effect on seropositive RA, a rare missense variant in STAT4 (rs140675301-A) that is independent of reported non-coding STAT4-variants, increases the risk of seropositive RA 2.27-fold (p=2.1x10(-9)), more than the rs2476601-A missense variant in PTPN22 (OR=1.59, p=1.3x10(-160)). STAT4 rs140675301-A replaces hydrophilic glutamic acid with hydrophobic valine (Glu128Val) in a conserved, surface-exposed loop. A stop-mutation (rs76428106-C) in FLT3 increases seropositive RA risk (OR=1.35, p=6.6x10(-11)). Independent missense variants in TYK2 (rs34536443-C, rs12720356-C, rs35018800-A, latter two novel) associate with decreased risk of seropositive RA (ORs=0.63-0.87, p=10(-9)-10(-27)) and decreased plasma levels of interferon-alpha/beta receptor 1 that signals through TYK2/JAK1/STAT4. Conclusion Sequence variants pointing to causal genes in the JAK/STAT pathway have largest effect on seropositive RA, while associations with seronegative RA remain scarce.
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