| 1. |
- Klasson, Lisa, et al.
(författare)
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Genome evolution of Wolbachia strain wPip from the Culex pipiens group.
- 2008
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Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 25:9, s. 1877-87
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Tidskriftsartikel (refereegranskat)abstract
- The obligate intracellular bacterium Wolbachia pipientis strain wPip induces cytoplasmic incompatibility (CI), patterns of crossing sterility, in the Culex pipiens group of mosquitoes. The complete sequence is presented of the 1.48-Mbp genome of wPip which encodes 1386 coding sequences (CDSs), representing the first genome sequence of a B-supergroup Wolbachia. Comparisons were made with the smaller genomes of Wolbachia strains wMel of Drosophila melanogaster, an A-supergroup Wolbachia that is also a CI inducer, and wBm, a mutualist of Brugia malayi nematodes that belongs to the D-supergroup of Wolbachia. Despite extensive gene order rearrangement, a core set of Wolbachia genes shared between the 3 genomes can be identified and contrasts with a flexible gene pool where rapid evolution has taken place. There are much more extensive prophage and ankyrin repeat encoding (ANK) gene components of the wPip genome compared with wMel and wBm, and both are likely to be of considerable importance in wPip biology. Five WO-B-like prophage regions are present and contain some genes that are identical or highly similar in multiple prophage copies, whereas other genes are unique, and it is likely that extensive recombination, duplication, and insertion have occurred between copies. A much larger number of genes encode ankyrin repeat (ANK) proteins in wPip, with 60 present compared with 23 in wMel, many of which are within or close to the prophage regions. It is likely that this pattern is partly a result of expansions in the wPip lineage, due for example to gene duplication, but their presence is in some cases more ancient. The wPip genome underlines the considerable evolutionary flexibility of Wolbachia, providing clear evidence for the rapid evolution of ANK-encoding genes and of prophage regions. This host-Wolbachia system, with its complex patterns of sterility induced between populations, now provides an excellent model for unraveling the molecular systems underlying host reproductive manipulation.
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| 2. |
- Scott, Robert A., et al.
(författare)
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A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease
- 2016
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 8:341
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Tidskriftsartikel (refereegranskat)abstract
- Regulatory authorities have indicated that new drugs to treat type 2 diabetes (T2D) should not be associated with an unacceptable increase in cardiovascular risk. Human genetics may be able to guide development of antidiabetic therapies by predicting cardiovascular and other health endpoints. We therefore investigated the association of variants in six genes that encode drug targets for obesity or T2D with a range of metabolic traits in up to 11,806 individuals by targeted exome sequencing and follow-up in 39,979 individuals by targeted genotyping, with additional in silico follow-up in consortia. We used these data to first compare associations of variants in genes encoding drug targets with the effects of pharmacological manipulation of those targets in clinical trials. We then tested the association of those variants with disease outcomes, including coronary heart disease, to predict cardiovascular safety of these agents. A low-frequency missense variant (Ala316Thr; rs10305492) in the gene encoding glucagon-like peptide-1 receptor (GLP1R), the target of GLP1R agonists, was associated with lower fasting glucose and T2D risk, consistent with GLP1R agonist therapies. The minor allele was also associated with protection against heart disease, thus providing evidence that GLP1R agonists are not likely to be associated with an unacceptable increase in cardiovascular risk. Our results provide an encouraging signal that these agents may be associated with benefit, a question currently being addressed in randomized controlled trials. Genetic variants associated with metabolic traits and multiple disease outcomes can be used to validate therapeutic targets at an early stage in the drug development process.
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| 3. |
- Toomey, Matthew B., et al.
(författare)
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Complementary shifts in photoreceptor spectral tuning unlock the full adaptive potential of ultraviolet vision in birds
- 2016
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Ingår i: eLife. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Color vision in birds is mediated by four types of cone photoreceptors whose maximal sensitivities (λmax) are evenly spaced across the light spectrum. In the course of avian evolution, the λmax of the most shortwave-sensitive cone, SWS1, has switched between violet (λmax > 400 nm) and ultraviolet (λmax < 380 nm) multiple times. This shift of the SWS1 opsin is accompanied by a corresponding short-wavelength shift in the spectrally adjacent SWS2 cone. Here, we show that SWS2 cone spectral tuning is mediated by modulating the ratio of two apocarotenoids, galloxanthin and 11',12'-dihydrogalloxanthin, which act as intracellular spectral filters in this cell type. We propose an enzymatic pathway that mediates the differential production of these apocarotenoids in the avian retina, and we use color vision modeling to demonstrate how correlated evolution of spectral tuning is necessary to achieve even sampling of the light spectrum and thereby maintain near-optimal color discrimination.
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| 4. |
- Ward, Sam M., et al.
(författare)
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Relative Intrinsic Scatter in Hierarchical Type Ia Supernova Sibling Analyses : Application to SNe 2021hpr, 1997bq, and 2008fv in NGC 3147
- 2023
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 956:2
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Tidskriftsartikel (refereegranskat)abstract
- We present Young Supernova Experiment grizy photometry of SN 2021hpr, the third Type Ia supernova sibling to explode in the Cepheid calibrator galaxy, NGC 3147. Siblings are useful for improving SN-host distance estimates and investigating their contributions toward the SN Ia intrinsic scatter (post-standardization residual scatter in distance estimates). We thus develop a principled Bayesian framework for analyzing SN Ia siblings. At its core is the cosmology-independent relative intrinsic scatter parameter, σRel: the dispersion of siblings distance estimates relative to one another within a galaxy. It quantifies the contribution toward the total intrinsic scatter, σ0, from within-galaxy variations about the siblings' common properties. It also affects the combined distance uncertainty. We present analytic formulae for computing a σRel posterior from individual siblings distances (estimated using any SN model). Applying a newly trained BAYESN model, we fit the light curves of each sibling in NGC 3147 individually, to yield consistent distance estimates. However, the wide σRel posterior means σRel ≈ σ0 is not ruled out. We thus combine the distances by marginalizing over σRel with an informative prior: σRel ∼ U(0, σ0). Simultaneously fitting the trio's light curves improves constraints on distance and each sibling's individual dust parameters, compared to individual fits. Higher correlation also tightens dust parameter constraints. Therefore, σRel marginalization yields robust estimates of siblings distances for cosmology, as well as dust parameters for sibling–host correlation studies. Incorporating NGC 3147's Cepheid distance yields H0 = 78.4 ± 6.5 km s−1 Mpc−1. Our work motivates analyses of homogeneous siblings samples, to constrain σRel and its SN-model dependence.
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