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- Gudbjartsson, Daniel F., et al.
(författare)
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Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 41:3, s. 342-347
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Tidskriftsartikel (refereegranskat)abstract
- Eosinophils are pleiotropic multifunctional leukocytes involved in initiation and propagation of inflammatory responses and thus have important roles in the pathogenesis of inflammatory diseases. Here we describe a genome-wide association scan for sequence variants affecting eosinophil counts in blood of 9,392 Icelanders. The most significant SNPs were studied further in 12,118 Europeans and 5,212 East Asians. SNPs at 2q12 (rs1420101), 2q13 (rs12619285), 3q21 (rs4857855), 5q31 (rs4143832) and 12q24 (rs3184504) reached genome-wide significance (P = 5.3 x 10(-14), 5.4 x 10(-10), 8.6 x 10(-17), 1.2 x 10(-10) and 6.5 x 10(-19), respectively). A SNP at IL1RL1 associated with asthma (P = 5.5 x 10(-12)) in a collection of ten different populations (7,996 cases and 44,890 controls). SNPs at WDR36, IL33 and MYB that showed suggestive association with eosinophil counts were also associated with atopic asthma (P = 4.2 x 10(-6), 2.2 x 10(-5) and 2.4 x 10(-4), respectively). We also found that a nonsynonymous SNP at 12q24, in SH2B3, associated significantly (P = 8.6 x 10(-8)) with myocardial infarction in six different populations (6,650 cases and 40,621 controls).
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| 7. |
- Berndt, Sonja I., et al.
(författare)
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Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
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Tidskriftsartikel (refereegranskat)abstract
- Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
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| 9. |
- Ebbesson, Lars, et al.
(författare)
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Neural circuits and their structural and chemical reorganization in the light-brain-pituitary axis during parr-smolt transformation in salmon
- 2003
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Ingår i: Aquaculture. - 0044-8486. ; 222:1-4, s. 59-70
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Tidskriftsartikel (refereegranskat)abstract
- Salmonid parr-smolt transformation (smoltification) is a transitional stage between freshwater and seawater life when the salmon imprint on their natal stream, change from a territorial feeding behavior to downstream migration, increase their hypoosmoregulatory competence, and change body shape and coloration. Photoperiod is recognized as the most potent initiator and regulator of the smoltification processes. Environmental light signals giving information about photoperiod are conveyed through a light-brain-pituitary axis that encompasses the neural pathways between photoreceptor organs, the brain and the pituitary, and the diurnal rhythm in melatonin secretion by the photosensory pineal organ. In addition, changes in photoperiod may elicit changes in this axis. Employing retinal neural tract tracing and growth associated protein-43 (GAP-43) immunocytochemistry, we provide here new evidence of a structural reorganization in the light-brain-pituitary axis during smoltification. Retinal tract tracing revealed that projections in smolts expand into new territories of the ipsilateral nucleus preopticus parvocellularis pars anterior (PPa) and additional fibers invade deeper into the contralateral PPa and the nucleus preopticus magnocellularis (PM). At this time, GAP-43-immunoreactive cells appear transiently in specific cell groups throughout the brain, but mainly in the olfactory bulb, telencephalon, and hypothalamus. These structural changes in the light-brain-pituitary axis and hypophysiotropic systems are followed by sequential surges of brain neurotransmitters and receptors, and occur prior to the major surges of circulating thyroid hormone and growth hormone levels that are central to smoltification-related processes. Our data point to a specific period of structural reorganization in certain brain circuits, and we hypothesize that these are involved in triggering the subsequent behavioral, endocrine, and physiological changes associated with smoltification. (C) 2003 Published by Elsevier Science B.V.
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| 10. |
- Ebbesson, LE, et al.
(författare)
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Nitric oxide synthase in the gill of Atlantic salmon: colocalization with and inhibition of Na+,K+-ATPase
- 2005
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Ingår i: Journal of Experimental Biology. - : The Company of Biologists. - 1477-9145 .- 0022-0949. ; 208:6, s. 1011-1017
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the relationship between nitric oxide (NO) and Na+,K+-ATPase (NKA) in the gill of anadromous Atlantic salmon. Cells containing NO-producing enzymes were revealed by means of nitric oxide synthase (NOS) immunocytochemistry and nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) histochernistry, which can be used as an indicator of NOS activity, i.e. NO production. Antibodies against the two constitutive NOS isoforms, neuronal and endothelial NOS, both produced immunoreactivity restricted to large cells at the base and along the secondary lamellae. NADPHd-positive cells showed a corresponding distribution. Antibodies against the inducible NOS isoform only labeled small cells located deep in the filament. Using in situ hybridization and NKA immunoreactivity, cells expressing Na+,K+-ATPase alpha-subunit mRNA were found to have a similar distribution to the NOS cells. Double labeling for NOS immunoreactivity and NKA cc-subunit mRNA revealed cellular colocalization of NKA alpha-subunit mRNA and nNOS protein in putative chloride cells at the base of the lamellae and interlamellar space. Along the lamellae, some NOS- or NKA-immunoreactive cells possessed a relatively lower expression of NKA a-subunit mRNA in smolts. A clear increase in NADPHd staining in the gill was demonstrated from parr to smolt. The regulatory role of NO on gill NKA activity was studied in vitro using sodium nitroprusside (SNP; 1 mmol l(-1)) and PAPA-NONOate (NOC-15; 0.5 mmol l(-1)) as NO donors. Both SNP and NOC-15 inhibited gill NKA activity by 30% when compared to controls. The study shows that NO systems are abundant in the gill of Atlantic salmon, that NO may be produced preferentially by a constitutive NOS isoform, and suggests that NO influence on gill functions is mediated via intracellular, possibly both auto/paracrine, inhibition of Na+,K+-ATPase activity in chloride cells. Furthermore, the increase in NADPHd in the gill during smoltification suggests a regulatory role of NO in the attenuation of the smoltification-related increase in Na+,K+-ATPase activity prior to entering seawater.
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