| 1. |
- Sodergren, Erica, et al.
(författare)
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The genome of the sea urchin Strongylocentrotus purpuratus.
- 2006
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 314:5801, s. 941-52
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Tidskriftsartikel (refereegranskat)abstract
- We report the sequence and analysis of the 814-megabase genome of the sea urchin Strongylocentrotus purpuratus, a model for developmental and systems biology. The sequencing strategy combined whole-genome shotgun and bacterial artificial chromosome (BAC) sequences. This use of BAC clones, aided by a pooling strategy, overcame difficulties associated with high heterozygosity of the genome. The genome encodes about 23,300 genes, including many previously thought to be vertebrate innovations or known only outside the deuterostomes. This echinoderm genome provides an evolutionary outgroup for the chordates and yields insights into the evolution of deuterostomes.
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| 2. |
- Soranzo, Nicole, et al.
(författare)
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A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:11, s. 38-1182
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Tidskriftsartikel (refereegranskat)abstract
- The number and volume of cells in the blood affect a wide range of disorders including cancer and cardiovascular, metabolic, infectious and immune conditions. We consider here the genetic variation in eight clinically relevant hematological parameters, including hemoglobin levels, red and white blood cell counts and platelet counts and volume. We describe common variants within 22 genetic loci reproducibly associated with these hematological parameters in 13,943 samples from six European population-based studies, including 6 associated with red blood cell parameters, 15 associated with platelet parameters and 1 associated with total white blood cell count. We further identified a long-range haplotype at 12q24 associated with coronary artery disease and myocardial infarction in 9,479 cases and 10,527 controls. We show that this haplotype demonstrates extensive disease pleiotropy, as it contains known risk loci for type 1 diabetes, hypertension and celiac disease and has been spread by a selective sweep specific to European and geographically nearby populations.
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| 3. |
- Rich, Rebecca L., et al.
(författare)
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A global benchmark study using affinity-based biosensors
- 2009
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Ingår i: Analytical Biochemistry. - : Elsevier BV. - 0003-2697 .- 1096-0309. ; 386:2, s. 194-216
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Tidskriftsartikel (refereegranskat)abstract
- To explore the variability in biosensor studies, 150 participants from 20 countries were given the same protein samples and asked to determine kinetic rate constants for the interaction. We chose a protein system that was amenable to analysis using different biosensor platforms as well as by users of different expertise levels. The two proteins (a 50-kDa Fab and a 60-kDa glutathione S-transferase [GST] antigen) form a relatively high-affinity complex, so participants needed to optimize several experimental parameters, including ligand immobilization and regeneration conditions as well as analyte concentrations and injection/dissociation times. Although most participants collected binding responses that could be fit to yield kinetic parameters, the quality of a few data sets could have been improved by optimizing the assay design. Once these outliers were removed, the average reported affinity across the remaining panel of participants was 620 pM with a standard deviation of 980 pM. These results demonstrate that when this biosensor assay was designed and executed appropriately, the reported rate constants were consistent, and independent of which protein was immobilized and which biosensor was used.
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| 4. |
- Sjöling, Sara, et al.
(författare)
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Benthic bacterial diversity and nutrient processes in mangroves : impact of deforestation
- 2005
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Ingår i: Estuarine, Coastal and Shelf Science. - United Kingdom : Academic Press. - 0272-7714 .- 1096-0015. ; 63:3, s. 397-406
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Tidskriftsartikel (refereegranskat)abstract
- The bacterial diversity and nutrient dynamics of mangrove sediments in Kisakasaka, Tanzania, was investigated in order to evaluate potential changes associated with deforestation of mangroves. Study sites included relatively undisturbed, recently protected mangroves and clear-cut mangrove areas that were sampled during both the wet and dry seasons. Physicochemical parameters, nitrogenase activity, pore water nutrient concentrations and bacterial diversity were measured in sediment depth profiles using both molecular and chemical techniques. Results show that there are significant differences in sediment pore water nutrient concentrations and bacterial diversity in sediments of mangrove areas which have been deforested compared to those which have been protected. Average measured values for protected and deforested areas, respectively, were: sulphide (S-2-),S- < 42 +/- 10 mu M and > 1.9 +/- 0.5 mM at 30 cm depth; ammonium (NH4+), 58 +/- 2 mu M and 113 +/- 12 mu M at 4-5 cm depth; soluble reactive phosphate, 40.2 +/- 11 mu M and 18.4 +/- 1.2 at 4-5 cm depth. Nitrogen fixation rates were lower in deforested areas during day and night, organic content was higher in protected areas (20 +/- 5%) compared to deforested areas (12 +/- 3%). The bacterial diversity was lower in deforested areas as determined by Shannon index using 16S rRNA gene analysis with terminal restriction fragment length polymorphism.
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| 5. |
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| 6. |
- Ben Rayana, Mohammed C., et al.
(författare)
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IFCC guideline for sampling, measuring and reporting ionized magnesium in plasma
- 2008
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Ingår i: Clinical Chemistry and Laboratory Medicine. - 1434-6621 .- 1437-4331. ; 46:1, s. 21-26
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Tidskriftsartikel (refereegranskat)abstract
- Analyzers with ion-selective electrodes (ISEs) for ionized magnesium (iMg) should yield comparable and unbiased results for iMg. This IFCC guideline on sampling, measuring and reporting iMg in plasma provides a prerequisite to achieve this goal [in this document, "plasma" refers to circulating plasma and the forms in which it is sampled, namely the plasma phase of anticoagulated whole blood (or "blood"), plasma separated from blood cells, or serum]. The guideline recommends measuring and reporting ionized magnesium as a substance concentration relative to the substance concentration of magnesium in primary aqueous calibrants with magnesium, sodium, and calcium chloride of physiological ionic strength. The recommended name is "the concentration of ionized magnesium in plasma". Based on this guideline, results will be approximately 3% higher than the true substance concentration and 4% lower than the true molality in plasma. Calcium ions interfere with all current magnesium ion-selective electrodes (Mg-ISEs), and thus it is necessary to determine both ions simultaneously in each sample and correct the result for Ca2+ interference. Binding of Mg in plasma is pH-dependent. Therefore, pH should be measured simultaneously with iMg to allow adjustment of the result to pH 7.4. The concentration of iMg in plasma may be physiologically and clinically more relevant than the concentration of total magnesium. Furthermore, blood-gas analyzers or instruments for point-of-care testing are able to measure plasma iMg using whole blood (with intact blood cells) as the sample, minimizing turnaround time compared to serum and plasma, which require removal of blood cells.
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| 7. |
- Ben Rayana, Mohammed C, et al.
(författare)
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Recommendation for measuring and reporting chloride by ISEs in undiluted serum, plasma or blood
- 2006
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Ingår i: Clinical Chemistry and Laboratory Medicine. - 1434-6621 .- 1437-4331. ; 44:3, s. 346-352
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Tidskriftsartikel (refereegranskat)abstract
- The proposed recommendation for measuring and reporting chloride in undiluted plasma† or blood by ion-selective electrodes (ISEs) will provide results that are identical to chloride concentrations measured by coulometry for standardized normal plasma or blood samples. It is applicable to all current ISEs dedicated to chloride measurement in undiluted samples that meet the requirements. However, in samples with reduced water concentration, results by coulometry are lower than by ion-selective electrode due to volume displacement. The quantity measured by this standardized ISE procedure is called the ionized chloride concentration. It may be clinically more relevant than the chloride concentration as determined by coulometry, photometry or by ISE after dilution of the sample. © 2006 by Walter de Gruyter.
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| 8. |
- Harley, M, et al.
(författare)
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Was Rodney Ledward a statistical outlier? Retrospective analysis using hospital data to identify gynaecologists performance
- 2005
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Ingår i: British Medical Journal, 2005, 330, 929.
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To investigate whether routinely collected data from hospital episode statistics could be used to identify the gynaecologist Rodney Ledward, who was suspended in 1966 and was the subject of the Ritchie inquiry into quality and practice within the NHS. Design A mixed scanning approach was used to identify seven variables from hospital episode statistics that were likely to be associated with potentially poor performance. A blinded multivariate analysis was undertaken to determine the distance (known as the Mahalanobis distance) in the seven indicator multidimensional space that each consultant was from the average consultant in each year. The change in Mahalanobis distance over time was also investigated by using a mixed effects model. Setting: NHS hospital trusts in two English regions, in the five years from 1991-2 to 1995-6. Population: Gynaecology consultants (n = 143) and their hospital episode statistics data. Main outcome measure Whether Ledward was a statistical outlier at the 95% level. Results: The proportion of consultants who were outliers in any one year (at the 95% significance level) ranged from 9% to 20%. Ledward appeared as an outlier in three of the five years. Our mixed effects (multi-year) model identified nine high outlier consultants, including Ledward. Conclusion: It was possible to identify Ledward as an outlier by using hospital episode statistics data. Although our method found other outlier consultants, we strongly caution that these outliers should not be overinterpreted as indicative of "poor" performance. Instead, a scientific search for a credible explanation should be undertaken, but this was outside the remit of our study. The set of indicators used means that cancer specialists, for example, are likely to have high values for several indicators, and the approach needs to be refined to deal with case mix variation. Even after allowing for that, the interpretation of outlier status is still as yet unclear. Further prospective evaluation of our method is warranted, but our overall approach may be potentially useful in other settings, especially where performance entails several indicator variables.
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| 9. |
- Haugaard-Kedström (published under the name Haugaard-Jönsson), Linda M., et al.
(författare)
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Structure of the R3/I5 chimeric relaxin peptide, a selective GPCR135 and GPCR142 agonist
- 2008
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 283:35, s. 23811-23818
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Tidskriftsartikel (refereegranskat)abstract
- The human relaxin family comprises seven peptide hormones with various biological functions mediated through interactions with G-protein-coupled receptors. Interestingly, among the hitherto characterized receptors there is no absolute selectivity toward their primary ligand. The most striking example of this is the relaxin family ancestor, relaxin-3, which is an agonist for three of the four currently known relaxin receptors: GPCR135, GPCR142, and LGR7. Relaxin-3 and its endogenous receptor GPCR135 are both expressed predominantly in the brain and have been linked to regulation of stress and feeding. However, to fully understand the role of relaxin-3 in neurological signaling, the development of selective GPCR135 agonists and antagonists for in vivo studies is crucial. Recent reports have demonstrated that such selective ligands can be achieved by making chimeric peptides comprising the relaxin-3 B-chain combined with the INSL5 A-chain. To obtain structural insights into the consequences of combining A-and B-chains from different relaxins we have determined the NMR solution structure of a human relaxin-3/INSL5 chimeric peptide. The structure reveals that the INSL5 A-chain adopts a conformation similar to the relaxin-3 A-chain, and thus has the ability to structurally support a native-like conformation of the relaxin-3 B-chain. These findings suggest that the decrease in activity at the LGR7 receptor seen for this peptide is a result of the removal of a secondary LGR7 binding site present in the relaxin-3 A-chain, rather than conformational changes in the primary B-chain receptor binding site.
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| 10. |
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