| 1. |
- Albrechtsen, A., et al.
(författare)
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Exome sequencing-driven discovery of coding polymorphisms associated with common metabolic phenotypes
- 2013
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 56:2, s. 298-310
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Tidskriftsartikel (refereegranskat)abstract
- Human complex metabolic traits are in part regulated by genetic determinants. Here we applied exome sequencing to identify novel associations of coding polymorphisms at minor allele frequencies (MAFs) > 1% with common metabolic phenotypes. The study comprised three stages. We performed medium-depth (8x) whole exome sequencing in 1,000 cases with type 2 diabetes, BMI > 27.5 kg/m(2) and hypertension and in 1,000 controls (stage 1). We selected 16,192 polymorphisms nominally associated (p < 0.05) with case-control status, from four selected annotation categories or from loci reported to associate with metabolic traits. These variants were genotyped in 15,989 Danes to search for association with 12 metabolic phenotypes (stage 2). In stage 3, polymorphisms showing potential associations were genotyped in a further 63,896 Europeans. Exome sequencing identified 70,182 polymorphisms with MAF > 1%. In stage 2 we identified 51 potential associations with one or more of eight metabolic phenotypes covered by 45 unique polymorphisms. In meta-analyses of stage 2 and stage 3 results, we demonstrated robust associations for coding polymorphisms in CD300LG (fasting HDL-cholesterol: MAF 3.5%, p = 8.5 x 10(-14)), COBLL1 (type 2 diabetes: MAF 12.5%, OR 0.88, p = 1.2 x 10(-11)) and MACF1 (type 2 diabetes: MAF 23.4%, OR 1.10, p = 8.2 x 10(-10)). We applied exome sequencing as a basis for finding genetic determinants of metabolic traits and show the existence of low-frequency and common coding polymorphisms with impact on common metabolic traits. Based on our study, coding polymorphisms with MAF above 1% do not seem to have particularly high effect sizes on the measured metabolic traits.
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| 2. |
- Andersen, Mette, et al.
(författare)
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Type 2 diabetes susceptibility gene variants predispose to adult-onset autoimmune diabetes
- 2014
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 57:9, s. 1859-1868
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis Latent autoimmune diabetes in adults (LADA) is phenotypically a hybrid of type 1 and type 2 diabetes. Genetically LADA is poorly characterised but does share genetic predisposition with type 1 diabetes. We aimed to improve the genetic characterisation of LADA and hypothesised that type 2 diabetes-associated gene variants also predispose to LADA, and that the associations would be strongest in LADA patients with low levels of GAD autoantibodies (GADA). Methods We assessed 41 type 2 diabetes-associated gene variants in Finnish (phase I) and Swedish (phase II) patients with LADA (n=911) or type 1 diabetes (n=406), all diagnosed after the age of 35 years, as well as in non-diabetic control individuals 40 years or older (n=4,002). Results Variants in the ZMIZ1 (rs12571751, p=4.1 x 10(-5)) and TCF7L2 (rs7903146, p=5.8 x 10(-4)) loci were strongly associated with LADA. Variants in the KCNQ1 (rs2237895, p=0.0012), HHEX (rs1111875, p=0.0024 in Finns) and MTNR1B (rs10830963, p=0.0039) loci showed the strongest association in patients with low GADA, supporting the hypothesis that the disease in these patients is more like type 2 diabetes. In contrast, variants in the KLHDC5 (rs10842994, p=9.5 x 10(-4) in Finns), TP53INP1 (rs896854, p=0.005), CDKAL1 (rs7756992, p=7.0 x 10(-4); rs7754840, p=8.8 x 10(-4)) and PROX1 (rs340874, p=0.003) loci showed the strongest association in patients with high GADA. For type 1 diabetes, a strong association was seen for MTNR1B (rs10830963, p=3.2 x 10(-6)) and HNF1A (rs2650000, p=0.0012). Conclusions/interpretation LADA and adult-onset type 1 diabetes share genetic risk variants with type 2 diabetes, supporting the idea of a hybrid form of diabetes and distinguishing them from patients with classical young-onset type 1 diabetes.
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| 3. |
- Andersson, Maria, et al.
(författare)
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Inhibition of kainic acid binding to glutamate receptors by extracts of Gastrodia
- 1995
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Ingår i: Phytochemistry. - 0031-9422. ; 38:4, s. 835-836
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Tidskriftsartikel (refereegranskat)abstract
- S-(4-hydroxybenzyl)glutathione was isolated as the major principle responsible for the inhibition of the in vitro binding of kainic acid to brain glutamate receptors by water extracts of the plant Gastrodia elata. The affinity (IC50 value) of the compound is slightly lower compared to glutamate and glutathione.
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| 4. |
- Andersson, Maria, et al.
(författare)
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Minor components with smooth muscle relaxing properties from scented myrrh (Commiphora guidotti)
- 1997
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Ingår i: Planta Medica. - : Georg Thieme Verlag KG. - 0032-0943 .- 1439-0221. ; 63:3, s. 251-254
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Tidskriftsartikel (refereegranskat)abstract
- All sesquiterpenes present in a sample of scented myrrh were isolated and characterised. Seven compounds, with cadinane, guaiane, oplopane, and eudesmane skeletons, were obtained, of which two are new and two are reported from a natural source for the first time. The major component, T-cadinol, has previously been shown to possess smooth muscle-relaxing properties, and the major purpose of the investigation was to compare the effects of the minor and more polar sesquiterpenes with that of T-cadinol in the rat aorta. Like T-cadinol, the minor sesquiterpenes are more efficient in reducing K(+)-induced contractions than those induced by the alpha-adrenoceptor agonist phenylephrine, however, they were all less potent than T-cadinol.
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| 5. |
- Berglund, Magnus, et al.
(författare)
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SAR studies of capsazepinoid bronchodilators 3: The thiourea part (coupling region) and the 2-(4-chlorophenyl)ethyl moiety (C-region).
- 2008
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Ingår i: Bioorganic & Medicinal Chemistry. - : Elsevier BV. - 0968-0896. ; 16:5, s. 2529-2540
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Tidskriftsartikel (refereegranskat)abstract
- Certain derivatives and analogues of capsazepine are potent in vitro inhibitors of bronchoconstriction in human small airways. During an investigation of the dependency of the potency on the structural features of the capsazepinoids in the thiourea moiety (coupling region) and the 2-(4-chlorophenyl)ethyl moiety (C-region), it was revealed that capsazepinoids with a thiourea or an amide link between the B-ring and the C-region in general have a good bronchorelaxing activity, while urea is a less attractive choice. Further, it was shown that 1,2,3,4-tetrahydroisoquinolines with a 2-(phenyl)ethyl derivative as the C-region are considerably more potent than those with an octyl group, while 2,3,4,5-tetrahydro-1H-2-benzazepines were found to be more insensitive to the nature of the C-region.
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| 6. |
- Berglund, Magnus, et al.
(författare)
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SAR studies of capsazepinoid bronchodilators. Part 2: Chlorination and catechol replacement in the A-ring.
- 2008
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Ingår i: Bioorganic & Medicinal Chemistry. - : Elsevier BV. - 0968-0896. ; 16:5, s. 2513-2528
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Tidskriftsartikel (refereegranskat)abstract
- Capsazepine as well as its derivatives and analogues are general inhibitors of constriction of human small airways. From a systematic variation of the capsazepine structure, divided into four regions, SARs were established. This paper concerns the chlorination of the A-ring as well as the replacement of the catechol with bioisosteric groups. It is revealed that chlorination of the A-ring has a profound effect on activity. Moreover, di-chlorination of the 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline structure results in a 10-fold increase in potency compared to capsazepine.
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| 7. |
- Dalence, Maria, et al.
(författare)
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SAR studies of capsazepinoid bronchodilators. Part 1: The importance of the catechol moiety and aspects of the B-ring structure.
- 2008
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Ingår i: Bioorganic & Medicinal Chemistry. - : Elsevier BV. - 0968-0896. ; 16:5, s. 2499-2512
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Tidskriftsartikel (refereegranskat)abstract
- Capsazepine as well as its derivatives and analogues are general inhibitors of constriction of human small airways. From a systematic variation of the capsazepine structure, divided into four regions, SARs were established. This part concerns the catechol moiety of the A-ring as well as the 2,3,4,5-tetrahydro-1H-2-azepine moiety (the B-ring) of capsazepine. It is revealed that a conformational constrain (as a fused ring) is important and that compounds with a six-membered B-ring (as a 1,2,3,4-tetrahydroisoquinoline) in general are more potent than the corresponding isoindoline, 2,3,4,5-tetrahydro-1H-2-benzazepine and 2,3,4,5-tetrahydro-1H-3-benzazepine derivatives.
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| 8. |
- Damon, Maria, 1977, et al.
(författare)
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Grandfathering: Environmental Uses and Impacts
- 2019
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Ingår i: Review of Environmental Economics and Policy. - : University of Chicago Press. - 1750-6824 .- 1750-6824 .- 1750-6816. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- “Grandfathering” grants preferential treatment to existing resource users over new entrants based on prior use. Grandfathering is based on the concept of first-in-time or prior appropriation and has been applied to a broad range of environmental and resource issues. We synthesize legal, economic, and political science perspectives and find that grandfathering removes incentives for users to anticipate regulations with proactive abatement. We analyze institutions ranging from long-enduring common-property regimes to climate negotiations to identify how grandfathering can be detrimental to sustainability, but we also show that it can be the only possible mechanism for bringing stakeholders to the table.
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| 9. |
- Damon, Maria, 1977, et al.
(författare)
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Policy Instruments for Sustainable Development at Rio +20
- 2012
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Ingår i: Journal of Environment and Development. - : SAGE Publications. - 1070-4965. ; 21:2, s. 143-151
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Tidskriftsartikel (refereegranskat)abstract
- Twenty years ago, governments gathered for the United Nations Conference on Environment and Development in Rio de Janeiro. The “Rio Declaration” laid out several principles of sustainable development, including the central role of policy instruments. In this article, we take stock of where we stand today in implementing sound and effective environmental policy instruments throughout the world, particularly in developing and transitional economies. We argue that, as our experience with market-based environmental policies has deepened over the past two decades, so has the ability to adapt instruments to complicated and heterogeneous contexts—but we are only just beginning, and the need to be further along is dire. One key factor may be that economists have not yet meaningfully accounted for the importance of political feasibility, which often hinges on risks to competitiveness and employment, or on the distribution of costs rather than on considerations of pure efficiency alone.
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| 10. |
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