| 1. |
- Abrahamson, Magnus, et al.
(författare)
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Structure and expression of the human cystatin C gene
- 1990
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Ingår i: Biochemical Journal. - 1470-8728. ; 268:2, s. 287-294
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Tidskriftsartikel (refereegranskat)abstract
- The structural organization of the gene for the human cysteine-proteinase inhibitor cystatin C was studied. Restriction-endonuclease digests of human genomic DNA hybridized with human cystatin C cDNA and genomic probes produced patterns consistent with a single cystatin C gene and, also, the presence of six closely related sequences in the human genome. A 30 kb restriction map covering the genomic region of the cystatin C gene was constructed. The positions of three polymorphic restriction sites, found at examination of digests of genomic DNA from 79 subjects, were localized in the flanking regions of the gene. The gene was cloned and the nucleotide sequence of a 7.3 kb genomic segment was determined, containing the three exons of the cystatin C structural gene as well as 1.0 kb of 5'-flanking and 2.0 kb of 3'-flanking sequences. Northern-blot experiments revealed that the cystatin C gene is expressed in every human tissue examined, including kidney, liver, pancreas, intestine, stomach, antrum, lung and placenta. The highest cystatin C expression was seen in seminal vesicles. The apparently non-tissue-specific expression of this cysteine-proteinase inhibitor gene is discussed with respect to the structure of its 5'-flanking region, which shares several features with those of housekeeping genes.
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| 2. |
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| 3. |
- Helgadottir, Anna, et al.
(författare)
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Genome-wide analysis yields new loci associating with aortic valve stenosis
- 2018
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Aortic valve stenosis (AS) is the most common valvular heart disease, and valve replacement is the only definitive treatment. Here we report a large genome-wide association (GWA) study of 2,457 Icelandic AS cases and 349,342 controls with a follow-up in up to 4,850 cases and 451,731 controls of European ancestry. We identify two new AS loci, on chromosome 1p21 near PALMD (rs7543130; odds ratio (OR) = 1.20, P = 1.2 × 10-22) and on chromosome 2q22 in TEX41 (rs1830321; OR = 1.15, P = 1.8 × 10-13). Rs7543130 also associates with bicuspid aortic valve (BAV) (OR = 1.28, P = 6.6 × 10-10) and aortic root diameter (P = 1.30 × 10-8), and rs1830321 associates with BAV (OR = 1.12, P = 5.3 × 10-3) and coronary artery disease (OR = 1.05, P = 9.3 × 10-5). The results implicate both cardiac developmental abnormalities and atherosclerosis-like processes in the pathogenesis of AS. We show that several pathways are shared by CAD and AS. Causal analysis suggests that the shared risk factors of Lp(a) and non-high-density lipoprotein cholesterol contribute substantially to the frequent co-occurence of these diseases.
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| 4. |
- Magnus, Fridrik, et al.
(författare)
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Current-voltage-time characteristics of the reactive Ar/N2 high power impulse magnetron sputtering discharge
- 2011
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Ingår i: Journal of Applied Physics. - : American Institute of Physics (AIP). - 0021-8979 .- 1089-7550. ; 110:8
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Tidskriftsartikel (refereegranskat)abstract
- The discharge current and voltage waveforms have been measured in a reactive high power impulse magnetron sputtering (HiPIMS) Ar/N2" role="presentation">N2 discharge with a Ti target for 400 μs" role="presentation">μs long pulses. We observe that the current waveform in the reactive Ar/N2" role="presentation">N2 HiPIMS discharge is highly dependent on the pulse repetition frequency, unlike the non-reactive Ar discharge. The current is found to increase significantly as the frequency is lowered. This is attributed to an increase in the secondary electron emission yield during the self-sputtering phase, when the nitride forms on the target at low frequencies. In addition, self-sputtering runaway occurs at lower discharge voltages when nitrogen is added to the discharge. This illustrates the crucial role of self-sputtering in the behavior of the reactive HiPIMS discharge.
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| 5. |
- Persson, Britt C., et al.
(författare)
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The ms2io6A37 modification of tRNA in Salmonella typhimurium regulates growth on citric acid cycle intermediates
- 1998
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Ingår i: Journal of Bacteriology. - 0021-9193. ; 180:12, s. 3144-3151
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Tidskriftsartikel (refereegranskat)abstract
- The modified nucleoside 2-methylthio-N-6-isopentenyl adenosine (ms(2)i(6)A) is present in position 37 (adjacent to and 3' of the anticodon) of tRNAs that read codons beginning with U except tRNA(I,V)(Ser) in Escherichia coli, In Salmonella typhimurium , 2-methylthio-N-6-(cis-hydroxy)isopentenyl adenosine (ms(2)io(6)A; also referred to as 2-methylthio cis-ribozeatin) is found in tRNA, most likely in the species that have ms(2)i(6)A in E. coli. Mutants (miaE) of S. typhimurium in which ms(2)i(6)A hydroxylation is blocked are unable to grow aerobically on the dicarboxylic acids of the citric acid cycle. Such mutants have normal uptake of dicarboxylic acids and functional enzymes of the citric acid cycle and the aerobic respiratory chain. The ability of S. typhimurium Bo grow ore succinate, fumarate, and malate is dependent on the state of modification in position 37 of those tRNAs normally having ms(2)io(6)A37 and is not due to a second cellular function of tRNA (ms(2)io(6)A37)hydroxylase, the miaE gene product. We suggest that S. typhimurium senses the hydroxylation status of the isopentenyl group of the tRNA and will grow on succinate, fumarate, or malate only if the isopentenyl group is hydroxylated.
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| 6. |
- Roegnvaldsson, Olafur, et al.
(författare)
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Numerical simulations of precipitation in the complex terrain of Iceland - Comparison with glaciological and hydrological data
- 2007
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Ingår i: Meteorologische Zeitschrift. - : Schweizerbart. - 1610-1227 .- 0941-2948. ; 16:1, s. 71-85
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Tidskriftsartikel (refereegranskat)abstract
- Atmospheric flow over Iceland has been simulated for the period September 1987 through June 2003, using the PSU/NCAR MM5 mesoscale model driven by initial and boundary data from the European Centre for Medium-range Weather Forecasts (ECMWF). The simulated precipitation is compared with two types of indirect precipitation observations. Firstly, snow accumulation on two large ice caps in SE-Iceland and on two large glaciers in central Iceland. Secondly, model output is used as input to the WaSiM-ETH hydrological model to calculate and compare the runoff with observed runoff from six watersheds in Iceland for the water years 1987-2002. Model precipitation compares favourably with both types of validation data. The seasonal and inter-annual variability of precipitation is investigated at low as well as high altitudes. The simulations reveal a negative trend in the winter precipitation in W-Iceland, but a positive trend in the ratio of lowland precipitation to mountain precipitation in E-Iceland. There is in general a substantial inter-annual variability in the ratio of lowland precipitation to precipitation in the mountains, especially in E-Iceland, emphasizing the limitation of precipitation observations in the lowlands as a proxy for precipitation in the mountains. In order to assess the impact of orography on the precipitation climate of Iceland, precipitation is simulated with flat Iceland and compared to a simulation with true orography. It is found that the mountains contribute to a total increase of precipitation in Iceland of the order of 40 %.
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| 7. |
- Stacey, Simon N, et al.
(författare)
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A germline variant in the TP53 polyadenylation signal confers cancer susceptibility.
- 2011
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 43:11, s. 1098-103
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Tidskriftsartikel (refereegranskat)abstract
- To identify new risk variants for cutaneous basal cell carcinoma, we performed a genome-wide association study of 16 million SNPs identified through whole-genome sequencing of 457 Icelanders. We imputed genotypes for 41,675 Illumina SNP chip-typed Icelanders and their relatives. In the discovery phase, the strongest signal came from rs78378222[C] (odds ratio (OR) = 2.36, P = 5.2 × 10(-17)), which has a frequency of 0.0192 in the Icelandic population. We then confirmed this association in non-Icelandic samples (OR = 1.75, P = 0.0060; overall OR = 2.16, P = 2.2 × 10(-20)). rs78378222 is in the 3' untranslated region of TP53 and changes the AATAAA polyadenylation signal to AATACA, resulting in impaired 3'-end processing of TP53 mRNA. Investigation of other tumor types identified associations of this SNP with prostate cancer (OR = 1.44, P = 2.4 × 10(-6)), glioma (OR = 2.35, P = 1.0 × 10(-5)) and colorectal adenoma (OR = 1.39, P = 1.6 × 10(-4)). However, we observed no effect for breast cancer, a common Li-Fraumeni syndrome tumor (OR = 1.06, P = 0.57, 95% confidence interval 0.88-1.27).
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| 8. |
- Wuttke, Matthias, et al.
(författare)
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A catalog of genetic loci associated with kidney function from analyses of a million individuals
- 2019
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Ingår i: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 51:6, s. 957-972
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Tidskriftsartikel (refereegranskat)abstract
- Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
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