| 1. |
- Wang, Thomas J, et al.
(författare)
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Common genetic determinants of vitamin D insufficiency: a genome-wide association study.
- 2010
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Ingår i: Lancet. - 1474-547X. ; 376:9736, s. 180-8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Vitamin D is crucial for maintenance of musculoskeletal health, and might also have a role in extraskeletal tissues. Determinants of circulating 25-hydroxyvitamin D concentrations include sun exposure and diet, but high heritability suggests that genetic factors could also play a part. We aimed to identify common genetic variants affecting vitamin D concentrations and risk of insufficiency. METHODS: We undertook a genome-wide association study of 25-hydroxyvitamin D concentrations in 33 996 individuals of European descent from 15 cohorts. Five epidemiological cohorts were designated as discovery cohorts (n=16 125), five as in-silico replication cohorts (n=9367), and five as de-novo replication cohorts (n=8504). 25-hydroxyvitamin D concentrations were measured by radioimmunoassay, chemiluminescent assay, ELISA, or mass spectrometry. Vitamin D insufficiency was defined as concentrations lower than 75 nmol/L or 50 nmol/L. We combined results of genome-wide analyses across cohorts using Z-score-weighted meta-analysis. Genotype scores were constructed for confirmed variants. FINDINGS: Variants at three loci reached genome-wide significance in discovery cohorts for association with 25-hydroxyvitamin D concentrations, and were confirmed in replication cohorts: 4p12 (overall p=1.9x10(-109) for rs2282679, in GC); 11q12 (p=2.1x10(-27) for rs12785878, near DHCR7); and 11p15 (p=3.3x10(-20) for rs10741657, near CYP2R1). Variants at an additional locus (20q13, CYP24A1) were genome-wide significant in the pooled sample (p=6.0x10(-10) for rs6013897). Participants with a genotype score (combining the three confirmed variants) in the highest quartile were at increased risk of having 25-hydroxyvitamin D concentrations lower than 75 nmol/L (OR 2.47, 95% CI 2.20-2.78, p=2.3x10(-48)) or lower than 50 nmol/L (1.92, 1.70-2.16, p=1.0x10(-26)) compared with those in the lowest quartile. INTERPRETATION: Variants near genes involved in cholesterol synthesis, hydroxylation, and vitamin D transport affect vitamin D status. Genetic variation at these loci identifies individuals who have substantially raised risk of vitamin D insufficiency. FUNDING: Full funding sources listed at end of paper (see Acknowledgments).
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| 2. |
- Amemiya, Chris T., et al.
(författare)
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The African coelacanth genome provides insights into tetrapod evolution
- 2013
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 496:7445, s. 311-316
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Tidskriftsartikel (refereegranskat)abstract
- The discovery of a living coelacanth specimen in 1938 was remarkable, as this lineage of lobe-finned fish was thought to have become extinct 70 million years ago. The modern coelacanth looks remarkably similar to many of its ancient relatives, and its evolutionary proximity to our own fish ancestors provides a glimpse of the fish that first walked on land. Here we report the genome sequence of the African coelacanth, Latimeria chalumnae. Through a phylogenomic analysis, we conclude that the lungfish, and not the coelacanth, is the closest living relative of tetrapods. Coelacanth protein-coding genes are significantly more slowly evolving than those of tetrapods, unlike other genomic features. Analyses of changes in genes and regulatory elements during the vertebrate adaptation to land highlight genes involved in immunity, nitrogen excretion and the development of fins, tail, ear, eye, brain and olfaction. Functional assays of enhancers involved in the fin-to-limb transition and in the emergence of extra-embryonic tissues show the importance of the coelacanth genome as a blueprint for understanding tetrapod evolution.
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| 3. |
- Marz, Manja, et al.
(författare)
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Animal snoRNAs and scaRNAs with exceptional structures
- 2011
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Ingår i: RNA Biology. - : Informa UK Limited. - 1547-6286 .- 1555-8584. ; 8:6, s. 938-946
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Tidskriftsartikel (refereegranskat)abstract
- The overwhelming majority of small nucleolar RNAs (snoRNAs) fall into two clearly defined classes characterized by distinctive secondary structures and sequence motifs. A small group of diverse ncRNAs, however, shares the hallmarks of one or both classes of snoRNAs but differs substantially from the norm in some respects. Here, we compile the available information on these exceptional cases, conduct a thorough homology search throughout the available metazoan genomes, provide improved and expanded alignments, and investigate the evolutionary histories of these ncRNA families as well as their mutual relationships.
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| 4. |
- Said, Safwat F, 1951-, et al.
(författare)
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Förstärkning av vägkonstruktion med stålnätsarmering : 12 års uppföljning av väg E6 Ljungskile
- 2014
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- En sträcka på 800 meter av motorvägen E6 söder om Ljungskile, öppnad för trafik 1991, uppvisade skador i form av längsgående sprickor i hjulspåren redan efter ca 5 års trafikering. Under år 2000 hade vägen omfattande längs- och tvärgående sprickbildning samt visade en omfattande spårbildning med ojämnheter. Sträckan förstärktes genom fräsning och påbyggnad. Inom vägavsnittet anlades tre provsträckor för undersökning av stålnätsarmeringens betydelse för upphöjning och förbättring av bärigheten och motståndet mot sprickor och spår. Teststräckorna instrumenterades med töjningsgivare på den frästa ytan. Syftet är att studera stålnätets förmåga att ge ökad bärighet i vägkroppen och motverka sprickor och spårbildning i beläggningsytan. Denna rapport redovisar resultat från uppföljning efter 12 års trafik. Efter att vägen har trafikerats i 12 år visar referenssträckan omfattande längsgående sprickor i hjulspår. Det förekommer inga tydliga bärighetsrelaterade sprickbildningar på de armerade sträckorna, utom en enstaka fin, längsgående spricka i en av de armerade sträckorna (sträcka 2) och ett par tvärgående, finare sprickor som kan härröra från skarvarna i stålarmeringen i sträcka 3. Det konstateras att armeringen har haft en signifikant effekt (10–15 %) på höjning av bärighet och begränsning av spårutveckling. Omfattande stensläpp på slitlagret har förekommit på alla tre sträckor.
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| 5. |
- Said, Safwat F., et al.
(författare)
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Prediction of flow rutting in asphalt concrete layers
- 2011
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Ingår i: The international journal of pavement engineering. - : Taylor & Francis Group. - 1029-8436 .- 1477-268X. ; 12:6, s. 519-532
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Tidskriftsartikel (refereegranskat)abstract
- This paper evaluates an approach for predicting rut formation in asphalt concrete (AC) layers. The approach is based on a linear viscoelastic model for predicting permanent vertical strain in AC layers subjected to a moving load. The input data are tyre pressure, loading speed, lateral wandering of loading wheel, shear modulus and phase angle of AC layer. The analytical approach takes into consideration the change in material characteristics in respect of temperature and changes in the air void content of AC layers due to repeated loading. The approach is verified by a full-scale accelerated loading test at different temperatures. The approach has shown good agreement as regards the prediction of flow rutting in AC layers. In addition, the approach is capable of calculating rutting profiles including the upheaval, which is important for estimating rut depth.
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