| 1. |
- Teslovich, Tanya M., et al.
(författare)
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Biological, clinical and population relevance of 95 loci for blood lipids
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 466:7307, s. 707-713
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Tidskriftsartikel (refereegranskat)abstract
- Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P<5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.
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| 2. |
- Richards, Stephen, et al.
(författare)
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Genome Sequence of the Pea Aphid Acyrthosiphon pisum
- 2010
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Ingår i: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 8:2, s. e1000313-
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Tidskriftsartikel (refereegranskat)abstract
- Aphids are important agricultural pests and also biological models for studies of insect-plant interactions, symbiosis, virus vectoring, and the developmental causes of extreme phenotypic plasticity. Here we present the 464 Mb draft genome assembly of the pea aphid Acyrthosiphon pisum. This first published whole genome sequence of a basal hemimetabolous insect provides an outgroup to the multiple published genomes of holometabolous insects. Pea aphids are host-plant specialists, they can reproduce both sexually and asexually, and they have coevolved with an obligate bacterial symbiont. Here we highlight findings from whole genome analysis that may be related to these unusual biological features. These findings include discovery of extensive gene duplication in more than 2000 gene families as well as loss of evolutionarily conserved genes. Gene family expansions relative to other published genomes include genes involved in chromatin modification, miRNA synthesis, and sugar transport. Gene losses include genes central to the IMD immune pathway, selenoprotein utilization, purine salvage, and the entire urea cycle. The pea aphid genome reveals that only a limited number of genes have been acquired from bacteria; thus the reduced gene count of Buchnera does not reflect gene transfer to the host genome. The inventory of metabolic genes in the pea aphid genome suggests that there is extensive metabolite exchange between the aphid and Buchnera, including sharing of amino acid biosynthesis between the aphid and Buchnera. The pea aphid genome provides a foundation for post-genomic studies of fundamental biological questions and applied agricultural problems.
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| 3. |
- Heap, Graham A., et al.
(författare)
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HLA-DQA1-HLA-DRB1 variants confer susceptibility to pancreatitis induced by thiopurine immunosuppressants
- 2014
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 46:10, s. 1131-1134
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Tidskriftsartikel (refereegranskat)abstract
- Pancreatitis occurs in approximately 4% of patients treated with the thiopurines azathioprine or mercaptopurine. Its development is unpredictable and almost always leads to drug withdrawal. We identified patients with inflammatory bowel disease (IBD) who had developed pancreatitis within 3 months of starting these drugs from 168 sites around the world. After detailed case adjudication, we performed a genome-wide association study on 172 cases and 2,035 controls with IBD. We identified strong evidence of association within the class II HLA region, with the most significant association identified at rs2647087 (odds ratio 2.59, 95% confidence interval 2.07-3.26, P = 2 x 10(-16)). We replicated these findings in an independent set of 78 cases and 472 controls with IBD matched for drug exposure. Fine mapping of the H LA region identified association with the HLA-DQA1*02:01-HLA-DRB1*07:01 haplotype. Patients heterozygous at rs2647087 have a 9% risk of developing pancreatitis after administration of a thiopurine, whereas homozygotes have a 17% risk.
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| 4. |
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| 5. |
- Boyd, Sally, 1949, et al.
(författare)
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Sociolinguistic practice among multilingual youth in Sweden and Canada
- 2011
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Ingår i: International symposium on bilingualism, 15-18 June, Oslo.
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Konferensbidrag (refereegranskat)abstract
- 2.Sociolinguistic Practice Among Multilingual Youth in Sweden and Canada This paper addresses two interrelated questions about the sociolinguistic identity and language use of young people in multilingual urban settings. First, can such speakers be divided into different groups on the basis of their sociolinguistic identity and native-speaker status? Second, to what extent does use of the majority language by multilingual youth differ from that of other majority-language speakers? These questions are of broad sociolinguistic interest, contributing more generally to the question of the extent to which the increasingly multilingual nature of formerly monolingual cities has resulted in relatively new ways of speaking, and what role multilingual speakers play in the local speech community. In this paper, we use quantitative methods to compare and contrast the results of a study of three urban centres in Sweden (Stockholm, Göteborg and Malmö) and one in Canada (Toronto). Findings of the studies in Sweden suggest that it is difficult not only to delineate homogeneous groups of speakers among multilingual urban youth, but also to find regular, cohesive patterns in sociolinguistic variation. Similarly, the Toronto study finds it difficult to delineate homogeneous groups, though speakers do seem to be distinguished on the basis of ethnic identity in their overall rates of use of certain variables. Some of these differences may be attributed to instantiations of and attitudes toward policies advocating multiculturalism in Sweden and Toronto. Taken together, the results of these studies suggest that new ways of speaking may be more fruitfully considered as a style of speech or an array of features selected from a pool of available resources for talk in certain contexts and for certain purposes, rather than as one or more ethnolects in the cities studied. These conclusions indicate that such ways of speaking are part and parcel of contemporary spoken Swedish and English. Summary: This paper compares identity and language use of youth in multilingual cities in Sweden and Canada. Examining speakers by (ethno)linguistic criteria and analysing linguistic variation, we find no homogeneous groupings, though some speakers may use particular styles or features as resources in certain contexts and for certain purposes.
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| 6. |
- Boyd, Sally, 1949, et al.
(författare)
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Storstadsungdomars deltagande i den pågående förändringen av ä-ljudet
- 2013
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Ingår i: Svenskans beskrivning 33, 15-17 maj 2013, Helsingfors.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Forskning om språkkontakt i Skandinaviens storstäder har ofta fokuserat på språkdrag vilka upplevs som nya och framträdande (bl a. Kotsinas 1994, Ganuza 2008, Svendsen & Røyneland 2008, Quist 2008, Källström & Lindberg 2011). I denna studie undersöker vi ett mindre framträdande språkdrag som har konstaterats vara under pågående förändring i svenska, nämligen öppningen av ä-ljudet, för att se om ungdomar med utländsk bakgrund deltar på samma sätt som övriga ungdomar i denna förändring (Leinonen 2010, Gross 2012). Det kan tänkas antingen 1) att språkförändringen påskyndas av språkkontakten, 2) att ungdomarna med utländsk bakgrund inte deltar i förändringsprocessen eller 3) att det inte finns signifikanta skillnader mellan ungdomar med olika bakgrunder vad gäller denna vokal. Vår kvantitativa studie bygger på fonetiska analyser av sociolingvistiska intervjuer med 60 ungdomar från olika stadsdelar i Göteborg och Stockholm; hälften av ungdomarna har svenskfödda mödrar och hälften utlandsfödda. Första och andra formanten av tre långa referensvokaler, /ɛ:/ mättes samt /ɛ:/ i kontexten framför /r/ , normaliserades och analyserades statistiskt. Resultaten visar att den allofoniska alterneringen mellan [ɛ:] och [æ:] framför /r/ och retroflexa konsonanter kan vara på väg att försvinna, åtminstone för vissa talare. Det visar sig också att de som ”leder utvecklingen” och har det öppnaste uttalet är tjejer, ungdomar bosatta i Stockholm och ungdomar med utlandsfödda mödrar. Vår preliminära slutsats är ändå att ungdomar med utländsk bakgrund deltar på samma sätt som övriga ungdomar i förändringsprocessen, eftersom andra bakgrundsvariabler (kön och stad) verkar spela större roll i förändringen än föräldrarnas ursprungsland.
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| 7. |
- Boyd, Sally, 1949, et al.
(författare)
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Variation and Change in the Vowels of Multilingual Swedish Youth
- 2013
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Ingår i: The 9th International Symposium on Bilingualism, 10-13 June 2013, Singapore. - 9789810767587
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Variation and Change in the Vowels of Multilingual Swedish Youth Sally Boyd 1,a , Johan Gross 1,b , Therese Leinonen 2,c and James Walker 3,d 1 University of Gothenburg, Sweden 2 Society of Swedish Literature in Finland 3 York University, Toronto, Canada a sally.boyd@gu.se, b gusgrosjo@student.gu.se, c therese.leinonen@gmail.com, d jamesw@york.ca Language contact in modern urban Scandinavia is the subject of recent studies (e.g. Kotsinas, 1994, Svendsen & Røyneland, 2008, Quist, 2008, Källström & Lindberg, 2011), which tend to focus on salient majority-language linguistic features used by multilingual youth of non-Scandinavian background in contrast with monolingual Scandinavian youth. However, many such features turn out to be infrequent or show no significant difference between monolingual and multilinguals (author1 et al., in press). In this study, we focus on less salient ongoing variation and change in the Swedish vowel system (author3, author2), to determine the extent to which multilingual urban youth in Sweden participate in ongoing changes. The data for this study come from recorded sociolinguistic interviews with mul- tilingual and monolingual youth in three cities. Using interviews with 60 speakers from Stockholm and Gothenburg, half of whom have Swedish as a second language or coordinate first language, we measured a representative sample of tokens of the first and second formant values for three long vowels, though here we focus on / ä :/. After coding the tokens for a series of linguistic and social factors, we used Rbrul (Johnson, 2009) to conduct regression analyses. Preliminary results show that youth in Stockholm tend to have higher F1 values than those in Gothenburg and a possible merger between allophones of / ä :/ before /r/ and elsewhere. Differences between multilinguals and monolinguals are small but statistically significant: monolinguals tend to produce a slightly more retracted [ Ä :] (i.e. they have a lower F2) than multilinguals. Furthermore, monolinguals with more diverse social networks tend to have values that are intermediate between other monolinguals and multilinguals.These results indicate that monolingual and multilingual Swedish youth participate fully in patterns of variation and change in the contemporary vowel system, though their pattern of participation may serve to identify them with the multicultural urban setting.
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| 8. |
- Dearing, John A., et al.
(författare)
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Safe and just operating spaces for regional social-ecological systems
- 2014
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Ingår i: Global Environmental Change. - : Elsevier BV. - 0959-3780 .- 1872-9495. ; 28, s. 227-238
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Tidskriftsartikel (refereegranskat)abstract
- Humanity faces a major global challenge in achieving wellbeing for all, while simultaneously ensuring that the biophysical processes and ecosystem services that underpin wellbeing are exploited within scientifically informed boundaries of sustainability. We propose a framework for defining the safe and just operating space for humanity that integrates social wellbeing into the original planetary boundaries concept (Rockstrom et al., 2009a,b) for application at regional scales. We argue that such a framework can: (1) increase the policy impact of the boundaries concept as most governance takes place at the regional rather than planetary scale; (2) contribute to the understanding and dissemination of complexity thinking throughout governance and policy-making; (3) act as a powerful metaphor and communication tool for regional equity and sustainability. We demonstrate the approach in two rural Chinese localities where we define the safe and just operating space that lies between an environmental ceiling and a social foundation from analysis of time series drawn from monitored and palaeoecological data, and from social survey statistics respectively. Agricultural intensification has led to poverty reduction, though not eradicated it, but at the expense of environmental degradation. Currently, the environmental ceiling is exceeded for degraded water quality at both localities even though the least well-met social standards are for available piped water and sanitation. The conjunction of these social needs and environmental constraints around the issue of water access and quality illustrates the broader value of the safe and just operating space approach for sustainable development.
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| 9. |
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| 10. |
- Lynch, Sally Ann, et al.
(författare)
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The 12q14 microdeletion syndrome : six new cases confirming the role of HMGA2 in growth
- 2011
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 19:5, s. 534-539
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Tidskriftsartikel (refereegranskat)abstract
- We report six patients with array deletions encompassing 12q14. Out of a total of 2538 array investigations carried out on children with developmental delay and dysmorphism in three diagnostic testing centres, six positive cases yielded a frequency of 1 in 423 for this deletion syndrome. The deleted region in each of the six cases overlaps significantly with previously reported cases with microdeletions of this region. The chromosomal range of the deletions extends from 12q13.3q15. In the current study, we report overlapping deletions of variable extent and size but primarily comprising chromosomal bands 12q13.3q14.1. Four of the six deletions were confirmed as de novo events. Two cases had deletions that included HMGA2, and both children had significant short stature. Neither case had osteopoikilosis despite both being deleted for LEMD3. Four cases had deletions that ended proximal to HMGA2 and all of these had much better growth. Five cases had congenital heart defects, including two with atrial septal defects, one each with pulmonary stenosis, sub-aortic stenosis and a patent ductus. Four cases had moderate delay, two had severe developmental delay and a further two had a diagnosis of autism. All six cases had significant speech delay with subtle facial dysmorphism.
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