| 1. |
- Aliu, E., et al.
(författare)
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Investigating the TeV Morphology of MGRO J1908+06 with VERITAS
- 2014
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 787:2
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Tidskriftsartikel (refereegranskat)abstract
- We report on deep observations of the extended TeV gamma-ray source MGRO J1908+06 made with the VERITAS very high energy gamma-ray observatory. Previously, the TeV emission has been attributed to the pulsar wind nebula (PWN) of theFermi-LAT pulsar PSR J1907+0602. We detect MGRO J1908+06 at a significance level of 14 standard deviations (14σ) and measure a photon index of 2.20 ± 0.10stat ± 0.20sys. The TeV emission is extended, covering the region near PSR J1907+0602 and also extending toward SNR G40.5-0.5. When fitted with a two-dimensional Gaussian, the intrinsic extension has a standard deviation of σsrc = 044 ± 002. In contrast to other TeV PWNe of similar age in which the TeV spectrum softens with distance from the pulsar, the TeV spectrum measured near the pulsar location is consistent with that measured at a position near the rim of G40.5-0.5, 033 away.
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| 2. |
- Aliu, E., et al.
(författare)
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Multiwavelength Observations of the TeV Binary LS I +61° 303 with VERITAS, Fermi-LAT, and Swift/XRT during a TeV Outburst
- 2013
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 779:1
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Tidskriftsartikel (refereegranskat)abstract
- We present the results of a multiwavelength observational campaign on the TeV binary system LS I +61° 303 with the VERITAS telescope array (>200 GeV), Fermi-LAT (0.3-300 GeV), and Swift/XRT (2-10 keV). The data were taken from 2011 December through 2012 January and show a strong detection in all three wavebands. During this period VERITAS obtained 24.9 hr of quality selected livetime data in which LS I +61° 303 was detected at a statistical significance of 11.9σ. These TeV observations show evidence for nightly variability in the TeV regime at a post-trial significance of 3.6σ. The combination of the simultaneously obtained TeV and X-ray fluxes do not demonstrate any evidence for a correlation between emission in the two bands. For the first time since the launch of the Fermi satellite in 2008, this TeV detection allows the construction of a detailed MeV-TeV spectral energy distribution from LS I +61° 303. This spectrum shows a distinct cutoff in emission near 4 GeV, with emission seen by the VERITAS observations following a simple power-law above 200 GeV. This feature in the spectrum of LS I +61° 303, obtained from overlapping observations with Fermi-LAT and VERITAS, may indicate that there are two distinct populations of accelerated particles producing the GeV and TeV emission.
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| 3. |
- Howe, LJ, et al.
(författare)
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Within-sibship genome-wide association analyses decrease bias in estimates of direct genetic effects
- 2022
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:65, s. 581-
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Tidskriftsartikel (refereegranskat)abstract
- Estimates from genome-wide association studies (GWAS) of unrelated individuals capture effects of inherited variation (direct effects), demography (population stratification, assortative mating) and relatives (indirect genetic effects). Family-based GWAS designs can control for demographic and indirect genetic effects, but large-scale family datasets have been lacking. We combined data from 178,086 siblings from 19 cohorts to generate population (between-family) and within-sibship (within-family) GWAS estimates for 25 phenotypes. Within-sibship GWAS estimates were smaller than population estimates for height, educational attainment, age at first birth, number of children, cognitive ability, depressive symptoms and smoking. Some differences were observed in downstream SNP heritability, genetic correlations and Mendelian randomization analyses. For example, the within-sibship genetic correlation between educational attainment and body mass index attenuated towards zero. In contrast, analyses of most molecular phenotypes (for example, low-density lipoprotein-cholesterol) were generally consistent. We also found within-sibship evidence of polygenic adaptation on taller height. Here, we illustrate the importance of family-based GWAS data for phenotypes influenced by demographic and indirect genetic effects.
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| 4. |
- Christoffersson, Gustaf, et al.
(författare)
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Interference with pancreatic sympathetic signaling halts the onset of diabetes in mice
- 2020
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 6:35
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Tidskriftsartikel (refereegranskat)abstract
- The notably lobular distribution of immune lesions in type 1 diabetes (T1D) has been hypothesized to be the result of innervation within the pancreas. To investigate whether neuroimmune interactions could explain this phenomenon, we explored the impact of sympathetic signaling in the RIP-LCMV-GP mouse model of autoimmune diabetes. In this model, the CD8(+) T cell attack on beta cells replicates a key pathogenic feature of human T1D. We found that inhibition of alpha(1) adrenoceptors, ablation of sympathetic nerves, and surgical denervation all had a protective effect in this model, without affecting the systemic presence of beta cell-reactive CD8(+) T cells. In vivo multiphoton imaging revealed a local effect within pancreatic islets including limited infiltration of both macrophages and beta cell-specific CD8(+) T cells. Islet-resident macrophages expressed adrenoceptors and were responsive to catecholamines. Islet macrophages may therefore constitute a pivotal neuroimmune signaling relay and could be a target for future interventions in T1D.
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| 5. |
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| 6. |
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| 7. |
- Schlosser, P, et al.
(författare)
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Meta-analyses identify DNA methylation associated with kidney function and damage
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 7174-
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Tidskriftsartikel (refereegranskat)abstract
- Chronic kidney disease is a major public health burden. Elevated urinary albumin-to-creatinine ratio is a measure of kidney damage, and used to diagnose and stage chronic kidney disease. To extend the knowledge on regulatory mechanisms related to kidney function and disease, we conducted a blood-based epigenome-wide association study for estimated glomerular filtration rate (n = 33,605) and urinary albumin-to-creatinine ratio (n = 15,068) and detected 69 and seven CpG sites where DNA methylation was associated with the respective trait. The majority of these findings showed directionally consistent associations with the respective clinical outcomes chronic kidney disease and moderately increased albuminuria. Associations of DNA methylation with kidney function, such as CpGs at JAZF1, PELI1 and CHD2 were validated in kidney tissue. Methylation at PHRF1, LDB2, CSRNP1 and IRF5 indicated causal effects on kidney function. Enrichment analyses revealed pathways related to hemostasis and blood cell migration for estimated glomerular filtration rate, and immune cell activation and response for urinary albumin-to-creatinineratio-associated CpGs.
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| 8. |
- Tin, A, et al.
(författare)
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Epigenome-wide association study of serum urate reveals insights into urate co-regulation and the SLC2A9 locus
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 7173-
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Tidskriftsartikel (refereegranskat)abstract
- Elevated serum urate levels, a complex trait and major risk factor for incident gout, are correlated with cardiometabolic traits via incompletely understood mechanisms. DNA methylation in whole blood captures genetic and environmental influences and is assessed in transethnic meta-analysis of epigenome-wide association studies (EWAS) of serum urate (discovery, n = 12,474, replication, n = 5522). The 100 replicated, epigenome-wide significant (p < 1.1E–7) CpGs explain 11.6% of the serum urate variance. At SLC2A9, the serum urate locus with the largest effect in genome-wide association studies (GWAS), five CpGs are associated with SLC2A9 gene expression. Four CpGs at SLC2A9 have significant causal effects on serum urate levels and/or gout, and two of these partly mediate the effects of urate-associated GWAS variants. In other genes, including SLC7A11 and PHGDH, 17 urate-associated CpGs are associated with conditions defining metabolic syndrome, suggesting that these CpGs may represent a blood DNA methylation signature of cardiometabolic risk factors. This study demonstrates that EWAS can provide new insights into GWAS loci and the correlation of serum urate with other complex traits.
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