| 1. |
- Zillikens, M. C., et al.
(författare)
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Large meta-analysis of genome-wide association studies identifies five loci for lean body mass
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass (n = 28,330) measured using dual energy X-ray absorptiometry or bioelectrical impedance analysis, adjusted for sex, age, height, and fat mass. Twenty-one single-nucleotide polymorphisms were significantly associated with lean body mass either genome wide (p < 5 x 10(-8)) or suggestively genome wide (p < 2.3 x 10(-6)). Replication in 63,475 (47,227 of European ancestry) individuals from 33 cohorts for whole body lean body mass and in 45,090 (42,360 of European ancestry) subjects from 25 cohorts for appendicular lean body mass was successful for five single-nucleotide polymorphisms in/ near HSD17B11, VCAN, ADAMTSL3, IRS1, and FTO for total lean body mass and for three single-nucleotide polymorphisms in/ near VCAN, ADAMTSL3, and IRS1 for appendicular lean body mass. Our findings provide new insight into the genetics of lean body mass.
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| 2. |
- Ahlm, Lars, et al.
(författare)
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Modeling the thermodynamics and kinetics of sulfuric acid-dimethylamine-water nanoparticle growth in the CLOUD chamber
- 2016
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Ingår i: Aerosol Science and Technology. - : Informa UK Limited. - 0278-6826 .- 1521-7388. ; 50:10, s. 1017-1032
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Tidskriftsartikel (refereegranskat)abstract
- Dimethylamine (DMA) has a stabilizing effect on sulfuric acid (SA) clusters, and the SA and DMA molecules and clusters likely play important roles in both aerosol particle formation and growth in the atmosphere. We use the monodisperse particle growth model for acid-base chemistry in nanoparticle growth (MABNAG) together with direct and indirect observations from the CLOUD4 and CLOUD7 experiments in the cosmics leaving outdoor droplets (CLOUD) chamber at CERN to investigate the size and composition evolution of freshly formed particles consisting of SA, DMA, and water as they grow to 20nm in dry diameter. Hygroscopic growth factors are measured using a nano-hygroscopicity tandem differential mobility analyzer (nano-HTDMA), which combined with simulations of particle water uptake using the thermodynamic extended-aerosol inorganics model (E-AIM) constrain the chemical composition. MABNAG predicts a particle-phase ratio between DMA and SA molecules of 1.1-1.3 for a 2nm particle and DMA gas-phase mixing ratios between 3.5 and 80 pptv. These ratios agree well with observations by an atmospheric-pressure interface time-of-flight (APi-TOF) mass spectrometer. Simulations with MABNAG, direct observations of the composition of clusters <2nm, and indirect observations of the particle composition indicate that the acidity of the nucleated particles decreases as they grow from approximate to 1 to 20nm. However, MABNAG predicts less acidic particles than suggested by the indirect estimates at 10nm diameter using the nano-HTDMA measurements, and less acidic particles than observed by a thermal desorption chemical ionization mass spectrometer (TDCIMS) at 10-30nm. Possible explanations for these discrepancies are discussed.
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| 3. |
- Bouchet, P., et al.
(författare)
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JWST MIRI Imager Observations of Supernova SN 1987A
- 2024
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 965:1
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Tidskriftsartikel (refereegranskat)abstract
- There exist very few mid-infrared (IR) observations of supernovae (SNe) in general. Therefore, SN 1987A, the closest visible SN in 400 yr, gives us the opportunity to explore the mid-IR properties of SNe, the dust in their ejecta, and the surrounding medium and to witness the birth of an SN remnant (SNR). The James Webb Space Telescope, with its high spatial resolution and extreme sensitivity, gives a new view on these issues. We report on the first imaging observations obtained with the Mid-InfraRed Instrument (MIRI). We build temperature maps and discuss the morphology of the nascent SNR. Our results show that the temperatures in the equatorial ring (ER) are quite nonuniform. This could be due to dust destruction in some parts of the ring, as had been assumed in some previous works. We show that the IR emission extends beyond the ER, illustrating the fact that the shock wave has now passed through this ring to affect the circumstellar medium on a larger scale. Finally, while submillimeter Atacama Large Millimeter Array observations have hinted at the location of the compact remnant of SN 1987A, we note that our MIRI data have found no such evidence.
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| 4. |
- Fransson, Claes, 1951-, et al.
(författare)
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Emission lines due to ionizing radiation from a compact object in the remnant of Supernova 1987A
- 2024
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 383:6685, s. 898-903
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Tidskriftsartikel (refereegranskat)abstract
- The nearby Supernova 1987A was accompanied by a burst of neutrino emission, which indicates that a compact object (a neutron star or black hole) was formed in the explosion. There has been no direct observation of this compact object. In this work, we observe the supernova remnant with JWST spectroscopy, finding narrow infrared emission lines of argon and sulfur. The line emission is spatially unresolved and blueshifted in velocity relative to the supernova rest frame. We interpret the lines as gas illuminated by a source of ionizing photons located close to the center of the expanding ejecta. Photoionization models show that the line ratios are consistent with ionization by a cooling neutron star or a pulsar wind nebula. The velocity shift could be evidence for a neutron star natal kick.
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| 5. |
- Holme, I, et al.
(författare)
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Cardiovascular outcomes and their relationships to lipoprotein components in patients with and without chronic kidney disease: results from the IDEAL trial
- 2010
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Ingår i: JOURNAL OF INTERNAL MEDICINE. - : Blackwell Publishing Ltd. - 0954-6820. ; 267:6, s. 567-575
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Tidskriftsartikel (refereegranskat)abstract
- Cardiovascular outcomes and their relationships to lipoprotein components in patients with and without chronic kidney disease: Results from the IDEAL trial. J Intern Med 2010; 267:567-575. Objectives. In Incremental Decrease in Endpoints through Aggressive Lipid-lowering (IDEAL), we compared cardiovascular outcomes in patients with and without chronic kidney disease (CKD) (estimated glomerular filtration rate andlt; 60 mL min-1 1.73 m-2) and analysed relationships between lipoprotein components (LC) and major coronary events (MCE) and other cardiovascular (CV) events. Design. Exploratory analysis of CV endpoints in a randomized trial comparing high dose of atorvastatin to usual dose of simvastatin on MCE. Settings. Patients with CKD were compared with the non-CKD patients. Cox regression models were used to study the relationships between on-treatment levels of LC and incident MCE. Findings. Chronic kidney disease was strongly associated with cardiovascular end-points including total mortality. In patients with CKD, a significant benefit of high dose atorvastatin treatment was found for any CV events, stroke and peripheral artery disease, but not for MCE. However, all cardiovascular end-points except stroke and CV mortality were reduced in the non-CKD group. Differential changes in LC or relationships to LC could not explain the different treatment outcomes in MCE in the two groups. Interpretation. Chronic kidney disease was a powerful risk factor for all cardiovascular end-points. The reason why the significant reductions achieved by high-dose statin treatment in most CV end-points in the non-CKD group were only in part matched by similar reductions in the CKD patients is not apparent. This difference did not result from differential changes in or relations to LC, but limited power may have increased the possibility of chance findings.
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| 6. |
- Holme, I., et al.
(författare)
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Lipoprotein predictors of cardiovascular events in statin-treated patients with coronary heart disease. Insights from the Incremental Decrease in End-points through Aggressive Lipid-lowering Trial (IDEAL)
- 2008
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Ingår i: Annals of Medicine. - : Informa UK Limited. - 0785-3890 .- 1365-2060. ; 40:6, s. 456-464
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Tidskriftsartikel (refereegranskat)abstract
- Background. Few studies have looked into the ability of measurements of apolipoprotein B (apoB) and apolipoprotein A-1 (apoA-1) or apoB/apoA-1 to predict new coronary heart disease (CHD) events in patients with CHD on statin treatment. Aims. In the IDEAL trial, to compare lipoprotein components to predict CHD events and to what degree differences in those parameters could explain the observed outcome. Methods. We compared the ability of treatment with atorvastatin 80 mg/day to that of simvastatin 20-40 mg/day to prevent CHD events in patients with CHD and used Cox regression models to study the relationships between on-treatment levels of lipoprotein components to subsequent major coronary events (MCE). Findings. Variables related to low-density lipoprotein cholesterol (LDL-C) carried more predictive information than those related to high-density lipoprotein cholesterol (HDL-C), but LDL-C was less predictive than both non-HDL-C and apoB. The ratio of apoB to apoA-1 was most strongly related to MCE. However, for estimating differences in relative risk reduction between the treatment groups, apoB and non-HDL-C were the strongest predictors. Interpretation. The on-treatment level of apoB/apoA-1 was the strongest predictor of MCE in the pooled patient population, whereas apoB and non-HDL-C were best able to explain the difference in outcome between treatment groups. Measurements of apoB and apoA-1 should be more widely available for routine clinical assessments. © 2008 Informa UK Ltd. (Informa Healthcare, Taylor & Francis AS).
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| 7. |
- Jiang, X., et al.
(författare)
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Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels
- 2018
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent). This larger GWAS yields two additional loci harboring genome-wide significant variants (P = 4.7x10(-9) at rs8018720 in SEC23A, and P = 1.9x10(-14) at rs10745742 in AMDHD1). The overall estimate of heritability of 25-hydroxyvitamin D serum concentrations attributable to GWAS common SNPs is 7.5%, with statistically significant loci explaining 38% of this total. Further investigation identifies signal enrichment in immune and hematopoietic tissues, and clustering with autoimmune diseases in cell-type-specific analysis. Larger studies are required to identify additional common SNPs, and to explore the role of rare or structural variants and gene-gene interactions in the heritability of circulating 25-hydroxyvitamin D levels.
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| 8. |
- Jones, O. C., et al.
(författare)
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Ejecta, Rings, and Dust in SN 1987A with JWST MIRI/MRS
- 2023
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 958:1
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Tidskriftsartikel (refereegranskat)abstract
- Supernova (SN) 1987A is the nearest supernova in ∼400 yr. Using the JWST MIRI Medium Resolution Spectrograph, we spatially resolved the ejecta, equatorial ring (ER), and outer rings in the mid-infrared 12,927 days (35.4 yr) after the explosion. The spectra are rich in line and dust continuum emission, both in the ejecta and the ring. The broad emission lines (280–380 km s−1 FWHM) that are seen from all singly-ionized species originate from the expanding ER, with properties consistent with dense post-shock cooling gas. Narrower emission lines (100–170 km s−1 FWHM) are seen from species originating from a more extended lower-density component whose high ionization may have been produced by shocks progressing through the ER or by the UV radiation pulse associated with the original supernova event. The asymmetric east–west dust emission in the ER has continued to fade, with constant temperature, signifying a reduction in dust mass. Small grains in the ER are preferentially destroyed, with larger grains from the progenitor surviving the transition from SN into SNR. The ER dust is fit with a single set of optical constants, eliminating the need for a secondary featureless hot dust component. We find several broad ejecta emission lines from [Ne ii], [Ar ii], [Fe ii], and [Ni ii]. With the exception of [Fe ii] 25.99 μm, these all originate from the ejecta close to the ring and are likely to be excited by X-rays from the interaction. The [Fe ii] 5.34 to 25.99 μm line ratio indicates a temperature of only a few hundred K in the inner core, which is consistent with being powered by 44 Ti decay.
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| 9. |
- Karasik, D., et al.
(författare)
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Disentangling the genetics of lean mass
- 2019
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 109:2, s. 276-287
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Tidskriftsartikel (refereegranskat)abstract
- Background: Lean body mass (LM) plays an important role in mobility and metabolic function. We previously identified five loci associated with LM adjusted for fat mass in kilograms. Such an adjustment may reduce the power to identify genetic signals having an association with both lean mass and fat mass. Objectives: To determine the impact of different fat mass adjustments on genetic architecture of LM and identify additional LM loci. Methods: We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age(2), and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms). Results: Seven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts. Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R). In contrast, loci with an impact specifically on LMwere termed "body builder" loci (VCAN and ADAMTSL3). Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection. Conclusions: In conclusion, we identified one novel LM locus (TNRC6B). Our results suggest that a genetically determined increase in lean mass might exert either harmful or protective effects on metabolic traits, depending on its relation to fat mass.
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| 10. |
- Larsson, Josefin, et al.
(författare)
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JWST NIRSpec Observations of Supernova 1987A : From the Inner Ejecta to the Reverse Shock
- 2023
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8205 .- 2041-8213. ; 949:2
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Tidskriftsartikel (refereegranskat)abstract
- We present initial results from JWST NIRSpec integral field unit observations of the nearby supernova SN 1987A. The observations provide the first spatially resolved spectroscopy of the ejecta and equatorial ring (ER) over the 1-5 μm range. We construct 3D emissivity maps of the [Fe i] 1.443 μm line from the inner ejecta and the He i 1.083 μm line from the reverse shock (RS), where the former probes the explosion geometry and the latter traces the structure of the circumstellar medium. We also present a model for the integrated spectrum of the ejecta. The [Fe i] 3D map reveals a highly asymmetric morphology resembling a broken dipole, dominated by two large clumps with velocities of ∼2300 km s−1. We also find evidence that the Fe-rich inner ejecta have started to interact with the RS. The RS surface traced by the He i line extends from just inside the ER to higher latitudes on both sides of the ER with a half-opening angle ∼45°, forming a bubble-like structure. The spectral model for the ejecta allows us to identify the many emission lines, including numerous H2 lines. We find that the H2 is most likely excited by far-UV emission, while the metal-line ratios are consistent with a combination of collisional excitation and recombination in the low-temperature ejecta. We also find several high-ionization coronal lines from the ER, requiring a temperature ≳2 × 106 K.
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