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| 2. |
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| 3. |
- Birney, Ewan, et al.
(author)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Journal article (peer-reviewed)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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| 4. |
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| 5. |
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| 6. |
- Wade, C. M., et al.
(author)
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Genome Sequence, Comparative Analysis, and Population Genetics of the Domestic Horse
- 2009
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 326:5954, s. 865-867
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Journal article (peer-reviewed)abstract
- We report a high-quality draft sequence of the genome of the horse ( Equus caballus). The genome is relatively repetitive but has little segmental duplication. Chromosomes appear to have undergone few historical rearrangements: 53% of equine chromosomes show conserved synteny to a single human chromosome. Equine chromosome 11 is shown to have an evolutionary new centromere devoid of centromeric satellite DNA, suggesting that centromeric function may arise before satellite repeat accumulation. Linkage disequilibrium, showing the influences of early domestication of large herds of female horses, is intermediate in length between dog and human, and there is long-range haplotype sharing among breeds.
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| 7. |
- Clark, Andrew G., et al.
(author)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Journal article (peer-reviewed)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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| 8. |
- Gretarsdottir, Solveig, et al.
(author)
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Genome-wide association study identifies a sequence variant within the DAB2IP gene conferring susceptibility to abdominal aortic aneurysm
- 2010
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:8, s. 71-692
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Journal article (peer-reviewed)abstract
- We performed a genome-wide association study on 1,292 individuals with abdominal aortic aneurysms (AAAs) and 30,503 controls from Iceland and The Netherlands, with a follow-up of top markers in up to 3,267 individuals with AAAs and 7,451 controls. The A allele of rs7025486 on 9q33 was found to associate with AAA, with an odds ratio (OR) of 1.21 and P = 4.6 x 10(-10). In tests for association with other vascular diseases, we found that rs7025486[A] is associated with early onset myocardial infarction (OR = 1.18, P = 3.1 x 10(-5)), peripheral arterial disease (OR = 1.14, P = 3.9 x 10(-5)) and pulmonary embolism (OR = 1.20, P = 0.00030), but not with intracranial aneurysm or ischemic stroke. No association was observed between rs7025486[A] and common risk factors for arterial and venous diseases-that is, smoking, lipid levels, obesity, type 2 diabetes and hypertension. Rs7025486 is located within DAB2IP, which encodes an inhibitor of cell growth and survival.
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| 9. |
- Lewin, Harris A., et al.
(author)
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The Earth BioGenome Project 2020 : Starting the clock
- 2022
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 119:4
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Journal article (other academic/artistic)
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| 10. |
- Naehrlich, L., et al.
(author)
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Incidence of SARS-CoV-2 in people with cystic fibrosis in Europe between February and June 2020
- 2021
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In: Journal of Cystic Fibrosis. - : Elsevier BV. - 1569-1993. ; 20:4, s. 566-577
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Journal article (peer-reviewed)abstract
- Background: Viral infections can cause significant morbidity in cystic fibrosis (CF). The current Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic could therefore have a serious impact on the health of people with CF (pwCF). Methods: We used the 38-country European Cystic Fibrosis Society Patient Registry (ECFSPR) to collect case data about pwCF and SARS-CoV-2 infection. Results: Up to 30 June 2020, 16 countries reported 130 SARS-CoV-2 cases in people with CF, yielding an incidence of 2.70/10 0 0 pwCF. Incidence was higher in lung-transplanted patients (n = 23) versus non transplanted patients (n = 107) (8.43 versus 2.36 cases/10 0 0). Incidence was higher in pwCF versus the age-matched general population in the age groups < 15, 15-24, and 25-49 years (p < 0.001), with similar trends for pwCF with and without lung transplant. Compared to the general population, pwCF (regardless of transplantation status) had significantly higher rates of admission to hospital for all age groups with available data, and higher rates of intensive care, although not statistically significant. Most pwCF recovered (96.2%), however 5 died, of whom 3 were lung transplant recipients. The case fatality rate for pwCF (3.85%, 95% CI: 1.26-8.75) was non-significantly lower than that of the general population (7.46%; p = 0.133). Conclusions: SARS-CoV-2 infection can result in severe illness and death for pwCF, even for younger patients and especially for lung transplant recipients. PwCF should continue to shield from infection and should be prioritized for vaccination. (c) 2021 The Authors. Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )
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| 11. |
- Christmas, Matthew, et al.
(author)
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Evolutionary constraint and innovation across hundreds of placental mammals
- 2023
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 380:6643
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Journal article (peer-reviewed)abstract
- Zoonomia is the largest comparative genomics resource for mammals produced to date. By aligning genomes for 240 species, we identify bases that, when mutated, are likely to affect fitness and alter disease risk. At least 332 million bases (similar to 10.7%) in the human genome are unusually conserved across species (evolutionarily constrained) relative to neutrally evolving repeats, and 4552 ultraconserved elements are nearly perfectly conserved. Of 101 million significantly constrained single bases, 80% are outside protein-coding exons and half have no functional annotations in the Encyclopedia of DNA Elements (ENCODE) resource. Changes in genes and regulatory elements are associated with exceptional mammalian traits, such as hibernation, that could inform therapeutic development. Earth's vast and imperiled biodiversity offers distinctive power for identifying genetic variants that affect genome function and organismal phenotypes.
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| 12. |
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| 13. |
- Adiels, Lars, 1952-, et al.
(author)
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Test of CP violation with K0 and K‾0 at LEAR
- 1985
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In: Physics with antiprotons at LEAR in the ACOL era. - Gif sur Yvette : Editions Frontières. - 2863320351 ; , s. 467-482
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Conference paper (other academic/artistic)
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| 14. |
- Busweiler, L A D, et al.
(author)
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International benchmarking in oesophageal and gastric cancer surgery
- 2019
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In: BJS Open. - : Oxford University Press (OUP). - 2474-9842. ; 3:1, s. 62-73
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Journal article (peer-reviewed)abstract
- Background: Benchmarking on an international level might lead to improved outcomes at a national level. The aim of this study was to compare treatment and surgical outcome data from the Swedish National Register for Oesophageal and Gastric Cancer (NREV) and the Dutch Upper Gastrointestinal Cancer Audit (DUCA).Methods: All patients with primary oesophageal or gastric cancer who underwent a resection and were registered in NREV or DUCA between 2012 and 2014 were included. Differences in 30-day mortality were analysed using case mix-adjusted multivariable logistic regression.Results: In total, 4439 patients underwent oesophagectomy (2509 patients) or gastrectomy (1930 patients). Estimated resection rates were comparable. Swedish patients were older but had less advanced disease and less co-morbidity than Dutch patients. Neoadjuvant treatment rates were lower in Sweden than in the Netherlands, both for patients who underwent oesophagectomy (68·6 versus 90·0 per cent respectively; P < 0·001) and for those having gastrectomy (38·3 versus 56·6 per cent; P < 0·001). In Sweden, transthoracic oesophagectomy was performed in 94·7 per cent of patients, whereas in the Netherlands, a transhiatal approach was undertaken in 35·8 per cent. Higher annual procedural volumes per hospital were observed in the Netherlands. Adjusted 30-day and/or in-hospital mortality after gastrectomy was statistically significantly lower in Sweden than in the Netherlands (odds ratio 0·53, 95 per cent c.i. 0·29 to 0·95).Conclusion: For oesophageal and gastric cancer, there are differences in patient, tumour and treatment characteristics between Sweden and the Netherlands. Postoperative mortality in patients with gastric cancer was lower in Sweden.
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| 15. |
- Cornelissen, Johannes H C, et al.
(author)
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Global negative vegetation feedback to climate warming responses of leaf litter decomposition rates in cold biomes
- 2007
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In: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 10:7, s. 619-627
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Journal article (peer-reviewed)abstract
- Whether climate change will turn cold biomes from large long-term carbon sinks into sources is hotly debated because of the great potential for ecosystem-mediated feedbacks to global climate. Critical are the direction, magnitude and generality of climate responses of plant litter decomposition. Here, we present the first quantitative analysis of the major climate-change-related drivers of litter decomposition rates in cold northern biomes worldwide.Leaf litters collected from the predominant species in 33 global change manipulation experiments in circum-arctic-alpine ecosystems were incubated simultaneously in two contrasting arctic life zones. We demonstrate that longer-term, large-scale changes to leaf litter decomposition will be driven primarily by both direct warming effects and concomitant shifts in plant growth form composition, with a much smaller role for changes in litter quality within species. Specifically, the ongoing warming-induced expansion of shrubs with recalcitrant leaf litter across cold biomes would constitute a negative feedback to global warming. Depending on the strength of other (previously reported) positive feedbacks of shrub expansion on soil carbon turnover, this may partly counteract direct warming enhancement of litter decomposition.
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| 16. |
- Costa, M, et al.
(author)
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Results from an ATM-based event builder demonstrator
- 1996
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In: IEEE TRANSACTIONS ON NUCLEAR SCIENCE. - : IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. - 0018-9499. ; 43:3, s. 1814-1820
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Journal article (other academic/artistic)abstract
- ATM switching fabrics are good candidates to implement high performance parallel event builders for the future data acquisition systems in particle physics experiments. We are studying their feasibility through simulations and implementation of event buil
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| 17. |
- Dieden, A., et al.
(author)
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Biomarkers associated with prevalent hypertension and higher blood pressure in a population-based cohort : a proteomic approach
- 2022
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In: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 43:Suppl 2, s. 2189-2189
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Journal article (other academic/artistic)abstract
- BackgroundGlobally, hypertension represents an enormous health issue as it is a major, yet modifiable risk factor for developing cardiovascular disease. Recently, chitinase-3-like protein 1 (CHI3L1) was shown to be positively associated with the incidence of hypertension among prehypertensive subjects, and variants of CHI3L1 gene were associated with both CHI3L1-levels and hypertension.PurposeTo explore associations between prevalent hypertension and blood pressure, and 92 proteins with involvement in inflammation and cardiovascular disease.MethodsPlasma samples from 1713 individuals from a Swedish population-based cohort (mean age 67.3±6.0 years; 28.9% women) were analysed with a proximity extension assay panel, consisting of 92 proteins. Prior to all analyses, subjects with prevalent cardiovascular disease, defined as having a history of prevalent coronary or stroke event, were excluded (n=189). Univariate logistic regression models were carried out exploring associations between each of the 92 proteins and prevalent hypertension, defined as systolic blood pressure ≥140 mmHg and/or a diastolic blood pressure ≥90 mmHg, or use of antihypertensive treatment (n=1168, 76.4%). Bonferroni-corrected significant associations between proteins and hypertension were further analysed using stepwise selection of covariates, namely age, body mass index, diabetes status, and cystatin C, in logistic regression models. Proteins with significant adjusted associations with prevalent hypertension were further analysed for associations with systolic and diastolic blood pressure individually in stepwise linear regression models. Complete data on all variables were available in 1527 subjects.ResultsSixteen proteins were significantly associated with prevalent hypertension in univariate analyses. After adjustment, three proteins remained significantly associated with prevalent hypertension (i.e., CHI3L1, low-density lipoprotein receptor (LDL receptor) and tissue plasminogen activator (tPA); Table 1). In analyses of associations with systolic blood pressure, CHI3L1 and LDL receptor showed significant associations. In analyses of associations with diastolic blood pressure, CHI3L1, LDL receptor and tPA showed significant associations (Table 1).ConclusionsHigher CHI3L1, tPA and LDL receptor levels were positively associated with prevalent hypertension after multivariable adjustment, among 1527 elderly subjects without established cardiovascular disease. Furthermore, higher CHI3L and LDL receptor levels were positively associated with mean systolic, as well as mean diastolic blood pressure in multivariable analyses.Funding AcknowledgementType of funding sources: Foundation. Main funding source(s): The Swedish Medical Research Council and The Swedish Heart and Lung Foundation
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| 18. |
- Gruen, E., et al.
(author)
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Ulysses Dust Detection System V3.1
- 2010
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In: NASA Planetary Data System. ; 140
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Journal article (peer-reviewed)abstract
- This data set contains the data from the Ulysses dust detector system (UDDS) from start of mission through the end of mission, 1990-2007. (As the dust detector was turned off after Nov. 30, 2007, this is the last date for which UDDS data is recorded.) Included are the dust impact data, noise data, laboratory calibration data, and location and orientation of the spacecraft and instrument.
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| 19. |
- Krüger, H., et al.
(author)
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Three years of Ulysses dust data: 1993-1995
- 1999
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In: Planetary and Space Science. - 1873-5088. ; 47:3-4, s. 363-383
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Journal article (peer-reviewed)abstract
- The Ulysses spacecraft is orbiting the Sun on a highly inclined ellipse (i = 79°). After its Jupiter flyby in 1992 at a heliocentric distance of 5.4 AU, the spacecraftreapproached the inner solar system, flew over the Suns south polar region in September 1994,crossed the ecliptic plane at a distance of 1.3 AU in March 1995, and flew over the Suns northpolar region in July 1995. We report on dust impact data obtained with the dust detector onboardUlysses between January 1993 and December 1995. We publish and analyse the complete dataset of 509 recorded impacts of dust particles with masses between 10-16 g-10-7 g. Together with 968 dust impacts from launch until the end of 1992 published earlier ([Gruuml;n et al., 1995c]), information about 1477 particles detected with theUlysses sensor between October 1990 and December 1995 is now available. The impact ratemeasured between 1993 and 1995 stayed relatively constant at about 0.4 impacts per day andvaried by less than a factor of ten. Most of the impacts recorded outside about 3.5 AU arecompatible with particles of interstellar origin. Two populations of interplanetary particles havebeen recognized: big micrometer-sized particles close to the ecliptic plane and smallsub-micrometer-sized particles at high ecliptic latitudes. The observed impact rate is comparedwith a model for the flux of interstellar dust particles which gives relatively good agreement withthe observed impact rate. No change in the instruments noise characteristics or degradation of thechanneltron could be revealed during the three-year period.
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| 20. |
- Kumagai, K., et al.
(author)
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Survival benefit and additional value of preoperative chemoradiotherapy in resectable gastric and gastro-oesophageal junction cancer : A direct and adjusted indirect comparison meta-analysis
- 2015
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In: European Journal of Surgical Oncology. - : Elsevier BV. - 0748-7983 .- 1532-2157. ; 41:3, s. 282-294
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Research review (peer-reviewed)abstract
- Several phase I/II studies of chemoradiotherapy for gastric cancer have reported promising results, but the significance of preoperative radiotherapy in addition to chemotherapy has not been proven. In this study, a systematic literature search was performed to capture survival and postoperative morbidity and mortality data in randomised clinical studies comparing preoperative (chemo)radiotherapy or chemotherapy versus surgery alone, or preoperative chemoradiotherapy versus chemotherapy for gastric and/or gastro-oesophageal junction (GOJ) cancer. Hazard ratios (HRs) for overall mortality were extracted from the original studies, individual patient data provided from the principal investigators of eligible studies or the earlier published meta-analysis. The incidences of postoperative morbidities and mortalities were also analysed. In total 18 studies were eligible and data were available from 14 of these. The meta-analysis on overall survival yielded HRs of 0.75 (95% CI 0.65-0.86, P < 0.001) for preoperative (chemo)radiotherapy and 0.83 (95% CI 0.67-1.01, P = 0.065) for preoperative chemotherapy when compared to surgery alone. Direct comparison between preoperative chemoradiotherapy and chemotherapy resulted in an HR of 0.71 (95% CI 0.45-1.12, P = 0.146). Combination of direct and adjusted indirect comparisons yielded an HR of 0.86 (95% CI 0.69-1.07, P = 0.171). No statistically significant differences were seen in the risk for postoperative morbidity or mortality between preoperative treatments and surgery alone, or preoperative (chemo)radiotherapy and chemotherapy. Preoperative (chemo)radiotherapy for gastric and GOJ cancer showed significant survival benefit over surgery alone. In comparisons between preoperative chemotherapy and (chemo)radiotherapy, there is a trend towards improved survival when adding radiotherapy, without increased postoperative morbidity or mortality.
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| 21. |
- Peng, Xinxia, et al.
(author)
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The draft genome sequence of the ferret (Mustela putorius furo) facilitates study of human respiratory disease
- 2014
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In: Nature Biotechnology. - : Springer Science and Business Media LLC. - 1087-0156 .- 1546-1696. ; 32:12, s. 1250-U114
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Journal article (peer-reviewed)abstract
- The domestic ferret (Mustela putorius furo) is an important animal model for multiple human respiratory diseases. It is considered the 'gold standard' for modeling human influenza virus infection and transmission(1-)4. Here we describe the 2.41 Gb draft genome assembly of the domestic ferret, constituting 2.28 Gb of sequence plus gaps. We annotated 19,910 protein-coding genes on this assembly using RNA-seq data from 21 ferret tissues. We characterized the ferret host response to two influenza virus infections by RNA-seq analysis of 42 ferret samples from influenza time-course data and showed distinct signatures in ferret trachea and lung tissues specific to 1918 or 2009 human pandemic influenza virus infections. Using microarray data from 16 ferret samples reflecting cystic fibrosis disease progression, we showed that transcriptional changes in the CFTR-knockout ferret lung reflect pathways of early disease that cannot be readily studied in human infants with cystic fibrosis disease.
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| 22. |
- Sandvik, R. M., et al.
(author)
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Contemporary N-2 and SF6 multiple breath washout in infants and toddlers with cystic fibrosis
- 2022
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In: Pediatric Pulmonology. - : Wiley. - 8755-6863 .- 1099-0496.
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Journal article (peer-reviewed)abstract
- Introduction Multiple breath washout (MBW) is used for early detection of cystic fibrosis (CF) lung disease, with SF6MBW commonly viewed as the reference method. The use of N2MBW in infants and toddlers has been questioned for technical and physiological reasons, but a new correction of the N(2 )signal has minimized the technical part. The present study aimed to assess the remaining differences and the contributing mechanisms for the differences between SF6 and N2MBW,corrected-such as tidal volume reduction during N-2 washout with pure O-2. Method This was a longitudinal multicenter cohort study. SF6MBW and N2MBW were performed prospectively at three CF centers in the same visits on 154 test occasions across 62 children with CF (mean age: 22.7 months). Offline analysis using identical algorithms to the commercially available program provided outcomes of N-2,N-original and N-2,N-corrected for comparison with SF6MBW. Results Mean functional residual capacity, FRCN2,corrected was 14.3% lower than FRCN2, original, and 1.0% different from FRCSF6. Lung clearance index, LCIN2,corrected was 25.2% lower than LCIN2,original, and 7.3% higher than LCISF6. Mean (SD) tidal volume decreased significantly during N2MBWcorrected, compared to SF6MBW (-13.1 ml [-30.7; 4.6], p < 0.0001, equal to -12.0% [-25.7; 1.73]), but this tidal volume reduction did not correlate to the differences between LCIN2,corrected and LCISF6. The absolute differences in LCI increased significantly with higher LCISF6 (0.63/LCISF6) and (0.23/LCISF6), respectively, for N-2,N-original and N-2,N-corrected, but the relative differences were stable across disease severity for N-2,N-corrected, but not for N-2,N-original. Conclusion Only minor residual differences between FRCN2,corrected and FRCSF6 remained to show that the two methods measure gas volumes very similar in this age range. Small differences in LCI were found. Tidal volume reduction during N2MBW did not affect differences. The corrected N2MBW can now be used with confidence in young children with CF, although not interchangeably with SF6.
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| 23. |
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| 24. |
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| 25. |
- Claassen, Y. H. M., et al.
(author)
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International comparison of treatment strategy and survival in metastatic gastric cancer
- 2019
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In: BJS Open. - : JOHN WILEY & SONS LTD. - 2474-9842. ; 3:1, s. 56-61
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Journal article (peer-reviewed)abstract
- BackgroundIn the randomized Asian REGATTA trial, no survival benefit was shown for additional gastrectomy over chemotherapy alone in patients with advanced gastric cancer with a single incurable factor, thereby discouraging surgery for these patients. The purpose of this study was to evaluate treatment strategies for patients with metastatic gastric cancer in daily practice in five European countries, along with relative survival in each country. MethodsNationwide population-based data from Belgium, Denmark, the Netherlands, Norway and Sweden were combined. Patients with primary metastatic gastric cancer diagnosed between 2006 and 2014 were included. The proportion of gastric resections performed and the administration of chemotherapy (irrespective of surgery) within each country were determined. Relative survival according to country was calculated. ResultsOverall, 15 057 patients with gastric cancer were included. The proportion of gastric resections varied from 81 per cent in the Netherlands and Denmark to 183 per cent in Belgium. Administration of chemotherapy was 392 per cent in the Netherlands, compared with 632 per cent in Belgium. The 6-month relative survival rate was between 390 (95 per cent c.i. 378 to 402) per cent in the Netherlands and 541 (521 to 569) per cent in Belgium. ConclusionThere is variation in the use of gastrectomy and chemotherapy in patients with metastatic gastric cancer, and subsequent differences in survival.
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| 26. |
- Cunningham, S. G., et al.
(author)
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Core Standards of the EUBIRO Project Defining a European Diabetes Data Dictionary for Clinical Audit and Healthcare Delivery
- 2016
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In: Methods of Information in Medicine. - : Georg Thieme Verlag KG. - 0026-1270 .- 2511-705X. ; 55:2, s. 166-176
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Journal article (peer-reviewed)abstract
- Background: A set of core diabetes indicators were identified in a clinical review of current evidence for the EUBIROD project. In order to allow accurate comparisons of diabetes indicators, a standardised currency for data storage and aggregation was required. We aimed to define a robust European data dictionary with appropriate clinical definitions that can be used to analyse diabetes outcomes and provide the foundation for data collection from existing electronic health records for diabetes. Methods: Existing clinical datasets used by 15 partner institutions across Europe were collated and common data items analysed for consistency in terms of recording, data definition and units of measurement. Where necessary, data mappings and algorithms were specified in order to allow partners to meet the standard definitions. A series of descriptive elements were created to document metadata for each data item, including recording, consistency, completeness and quality. Results: While datasets varied in terms of consistency, it was possible to create a common standard that could be used by all. The minimum dataset defined 53 data items that were classified according to their feasibility and validity. Mappings and standardised definitions were used to create an electronic directory for diabetes care, providing the foundation for the EUBIROD data analysis repository, also used to implement the diabetes registry and model of care for Cyprus. Conclusions: The development of data dictionaries and standards can be used to improve the quality and comparability of health information. A data dictionary has been developed to be compatible with other existing data sources for diabetes, within and beyond Europe.
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| 27. |
- Frantz, A M, et al.
(author)
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Molecular Profiling Reveals Prognostically Significant Subtypes of Canine Lymphoma
- 2013
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In: Veterinary pathology. - : SAGE Publications. - 0300-9858 .- 1544-2217. ; 50:4, s. 693-703
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Journal article (peer-reviewed)abstract
- We performed genomewide gene expression analysis of 35 samples representing 6 common histologic subtypes of canine lymphoma and bioinformatics analyses to define their molecular characteristics. Three major groups were defined on the basis of gene expression profiles: (1) low-grade T-cell lymphoma, composed entirely by T-zone lymphoma; (2) high-grade T-cell lymphoma, consisting of lymphoblastic T-cell lymphoma and peripheral T-cell lymphoma not otherwise specified; and (3) B-cell lymphoma, consisting of marginal B-cell lymphoma, diffuse large B-cell lymphoma, and Burkitt lymphoma. Interspecies comparative analyses of gene expression profiles also showed that marginal B-cell lymphoma and diffuse large B-cell lymphoma in dogs and humans might represent a continuum of disease with similar drivers. The classification of these diverse tumors into 3 subgroups was prognostically significant, as the groups were directly correlated with event-free survival. Finally, we developed a benchtop diagnostic test based on expression of 4 genes that can robustly classify canine lymphomas into one of these 3 subgroups, enabling a direct clinical application for our results.
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| 28. |
- Grun, E., et al.
(author)
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South-North and Radial Traverses through the Interplanetary Dust Cloud
- 1997
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In: Icarus. - : Elsevier BV. - 0019-1035. ; 129:2, s. 270-288
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Journal article (peer-reviewed)abstract
- Identical in situ dust detectors are flown on board the Galileo and Ulysses spacecraft. They record impacts of micrometeoroids in the ecliptic plane at heliocentric distances from 0.7 to 5.4 AU and in a plane almost perpendicular to the ecliptic from -79 deg to +79 deg ecliptic latitude. The combination of both Ulysses and Galileo measurements yields information about the radial and latitudinal distributions of micron- and sub-micron-sized dust in the Solar System. Two types of dust particles were found to dominate the dust flux in interplanetary space. Interplanetary micrometeoroids covering a wide mass range from 10^-16 to 10^-6 g are recorded mostly inside 3 AU and at latitudes below 30 deg. Interstellar grains with masses between 10^-14 and 10^-12 g have been positively identified outside 3 AU near the ecliptic plane and outside 1.8 AU at high ecliptic latitudes (>50 deg). Interstellar grains move on hyperbolic trajectories through the planetary system and constitute the dominant dust flux (1.5 x 10^-4 m^-2 sec^-1) in the outer Solar System and at high ecliptic latitudes. To compare and analyze the Galileo and Ulysses data sets, a new model is developed based on J. Geophys. Res. 98, 17029-17048, Divine's (1993, ``five populations of interplanetary meteoroids'' model. Both models describe the interplanetary meteoroid environment in terms of dust populations on distinct orbits. Taking into account the measured velocities and the effect of radiation pressure on small particles (described by the ratio of radiation pressure force to gravity, beta), we define four populations of meteoroids on elliptical orbits and one population on hyperbolic orbit that can fit the micrometeoroid flux observed by Galileo and Ulysses. Micrometeoroids with masses greater than 10^-10 g and negligible radiation pressure (beta = 0) orbit the Sun on low to moderately eccentric orbits and with low inclinations (<=30 deg). Populations of smaller particles with mean masses of 10^-11 g (beta = 0.3), 10^-13 g (beta = 0.8), and 5 x 10^-15 g (beta = 0.3), respectively, have components with high eccentricities and have increasingly wider inclination distributions with decreasing mass. Similarities among the orbit distributions of the small particle populations on bound orbits suggest that all are genetically related and are part of an overall micrometeoroid complex that prevails in the inner Solar System. The high-eccentricity component of the small particle populations may actually be beta-meteoroids which are not well characterized by our measurements. Our modeling suggests further that the interstellar dust flux is not reduced at Ulysses' perihelion distance (1.3 AU) and that it contributes about 30% of the total dust flux observed there.
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| 29. |
- Helgadottir, Anna, et al.
(author)
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Apolipoprotein(a) Genetic Sequence Variants Associated With Systemic Atherosclerosis and Coronary Atherosclerotic Burden But Not With Venous Thromboembolism
- 2012
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In: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 60:8, s. 722-729
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Journal article (peer-reviewed)abstract
- Objectives The purpose of this study is investigate the effects of variants in the apolipoprotein(a) gene (LPA) on vascular diseases with different atherosclerotic and thrombotic components. Background It is unclear whether the LPA variants rs10455872 and rs3798220, which correlate with lipoprotein(a) levels and coronary artery disease (CAD), confer susceptibility predominantly via atherosclerosis or thrombosis. Methods The 2 LPA variants were combined and examined as LPA scores for the association with ischemic stroke (and TOAST [Trial of Org 10172 in Acute Stroke Treatment] subtypes) (effective sample size [n(e)] = 9,396); peripheral arterial disease (n(e) = 5,215); abdominal aortic aneurysm (ne = 4,572); venous thromboembolism (ne = 4,607); intracranial aneurysm (ne = 1,328); CAD (n(e) = 12,716), carotid intima-media thickness (n = 3,714), and angiographic CAD severity (n = 5,588). Results LPA score was associated with ischemic stroke subtype large artery atherosclerosis (odds ratio [OR]: 1.27; p = 6.7 X 10(-4)), peripheral artery disease (OR: 1.47; p = 2.9 x 10(-14)), and abdominal aortic aneurysm (OR: 1.23; p = 6.0 x 10(-5)), but not with the ischemic stroke subtypes cardioembolism (OR: 1.03; p = 0.69) or small vessel disease (OR: 1.06; p = 0.52). Although the LPA variants were not associated with carotid intima-media thickness, they were associated with the number of obstructed coronary vessels (p = 4.8 x 10(-12)). Furthermore, CAD cases carrying LPA risk variants had increased susceptibility to atherosclerotic manifestations outside of the coronary tree (OR: 1.26; p = 0.0010) and had earlier onset of CAD (-1.58 years/allele; p = 8.2 x 10(-8)) than CAD cases not carrying the risk variants. There was no association of LPA score with venous thromboembolism (OR: 0.97; p = 0.63) or intracranial aneurysm (OR: 0.85; p = 0.15). Conclusions LPA sequence variants were associated with atherosclerotic burden, but not with primarily thrombotic phenotypes. (J Am Coll Cardiol 2012; 60: 722-9) (C) 2012 by the American College of Cardiology Foundation
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| 30. |
- Helgadottir, Anna, et al.
(author)
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The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm
- 2008
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:2, s. 217-224
-
Journal article (peer-reviewed)abstract
- Recently, two common sequence variants on 9p21, tagged by rs10757278-G and rs10811661-T, were reported to be associated with coronary artery disease (CAD)(1-4) and type 2 diabetes (T2D)(5-7), respectively. We proceeded to further investigate the contributions of these variants to arterial diseases and T2D. Here we report that rs10757278-G is associated with, in addition to CAD, abdominal aortic aneurysm (AAA; odds ratio (OR) 1.31, P = 1.2 x 10(-12)) and intracranial aneurysm (OR = 1.29, P = 2.5 x 10(-6)), but not with T2D. This variant is the first to be described that affects the risk of AAA and intracranial aneurysm in many populations. The association of rs10811661-T to T2D replicates in our samples, but the variant does not associate with any of the five arterial diseases examined. These findings extend our insight into the role of the sequence variant tagged by rs10757278-G and show that it is not confined to atherosclerotic diseases.
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| 31. |
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| 32. |
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| 33. |
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| 34. |
- Korduner, Johan, et al.
(author)
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Galectin-4 levels in hospitalized versus non-hospitalized subjects with obesity: the Malmo Preventive Project
- 2022
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In: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 21:1
-
Journal article (peer-reviewed)abstract
- Background Obesity is strongly associated with the development of cardiovascular disease (CVD). However, the heterogenous nature of obesity in CVD-risk is still poorly understood. We aimed to explore novel CVD biomarkers and their possible association with presumed unhealthy obesity, defined as hospitalized subjects with obesity (HO). Methods Ninety-two proteins associated with CVD were analyzed in 517 (mean age 67 +/- 6 years; 33.7% women) individuals with obesity (BMI >= 30 kg/m(2)) from the Malmo Preventive Project cohort, using a proximity extension array technique from the Olink CVD III panel. Individuals with at least one recorded hospitalization for somatic disease prior to study baseline were defined as HO phenotypes. Associations between proteins and HO (n = 407) versus non-hospitalized subjects with obesity (NHO, n = 110), were analyzed using multivariable binary logistic regression, adjusted for traditional risk factors. Results Of 92 analyzed unadjusted associations between biomarkers and HO, increased levels of two proteins were significant at a false discovery rate < 0.05: Galectin-4 (Gal-4) and insulin-like growth factor-binding protein 1 (IGFBP-1). When these two proteins were included in logistic regression analyses adjusted for age and sex, Gal-4 remained significant. Gal-4 was independently associated with the HO phenotype in multivariable logistic regression analysis (OR 1.72; CI95% 1.16-2.54). Post-hoc analysis revealed that this association was only present in the subpopulation with diabetes (OR 2.26; CI95% 1.25-4.07). However, an interaction analysis was performed, showing no significant interaction between Gal-4 and prevalent diabetes (p = 0.16). Conclusions In middle-aged and older individuals with obesity, increased Gal-4 levels were associated with a higher probability of HO. This association was only significant in subjects with diabetes only, further implying a role for Gal-4 in diabetes and its complications.
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| 35. |
- Krueger, H., et al.
(author)
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Five years of Ulysses dust data: 2000-2004
- 2006
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In: Planetary and Space Science. - : Elsevier BV. - 1873-5088 .- 0032-0633. ; 54:9-10, s. 932-956
-
Journal article (peer-reviewed)abstract
- The Ulysses spacecraft has been orbiting the Sun on a highly inclined ellipse (i = 79 degrees, perihelion distance 1.3 AU, aphelion distance 5.4 AU) since it encountered Jupiter in 1992. Between January 2000 and December 2004, the spacecraft completed almost an entire revolution about the Sun, passing through perihelion in May 2001 and aphelion in July 2004. In this five-year period the dust detector on board recorded 4415 dust impacts. We publish and analyse the complete data set of both raw and reduced data for particles with masses 10(-16) g <= M <= 10(-7) g. Together with. 1695 dust impacts recorded between launch of Ulysses and the end of 1999 published earlier (Grain, E., Baguhl, M., Divine, N., Fechtig, H., Hamilton, D.P, Harmer, M.S., Kissel, J., Lindblad, B.A., Linkert, D., Linkert, G., Mann, L, McDonnell, J.A.M., Morfill, G.E., Polanskey, C., Riemann, R., Schwehm, G.H., Siddique, N., Staubach, P., Zook, H.A., 1995a. Two years of Ulysses dust data. Planetary Space Sci. 43, 971-999, Paper III; Kruger, H., Grun, E., Landgraf, M., Baguhl, M., Dermott, S.F., Fechtig, H., Gustafson, B.A., Hamilton, D.P., Harmer, M.S., Horanyi, M., Kissel, J., Lindblad, B., Linkert, D., Linkert, G., Mann, L, McDonnell, J.A.M., Morfill, G.E., Polanskey, C., Schwehm, G.H., Srama, R., Zook, H.A., 1995. Three years of Ulysses dust data: 1993 to 1995. Planetary and Space Sci. 47, 363-383, Paper V; Kruger, H., Grun, E., Landgraf, M., Dermott, S.F., Fechtig, H., Gustafson, B.A., Hamilton, D.P., Harmer, M.S., Horanyi, M., Kissel, J., Lindblad, B., Linkert, D., Linkert, G., Mann, I., McDonnell, J.A.M., Morfill, G.E., Polanskey, C., Schwehm, G.H., Srama, R., Zook, H.A., 2001b. Four years of Ulysses dust data: 1996 to 1999. Planetary Space Sci. 49, 1303-1324, Paper VII), a data set of 6110 dust impacts detected with the Ulysses sensor between October 1990 and December 2004 is now available. The impact rate measured between 2000 and 2002 was relatively constant with about 0.3 impacts per day showing a maximum at 1.5 per day around ecliptic plane crossing in early-2001. The impact direction of the majority of impacts between 2000 and 2002 is compatible with particles of interstellar origin, the rest are most likely interplanetary particles. In 2003 and 2004 dust stream particles originating from the jovian system dominated the overall impact rate. Twenty-two individual dust streams were measured between November 2002 and December 2004. The observed impact rates are compared with models for interplanetary and interstellar dust. The dust measurements from the entire mission since Ulysses launch give good agreement with the interplanetary flux model of Staubach, P., Grun, E., Jehn, R., 1997. The meteoroid environment near Earth, Adv. Space Res. 19, 301-308. (c) 2006 Elsevier Ltd. All rights reserved.
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| 36. |
- Krueger, H., et al.
(author)
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Galileo Dust Detection System V4.1
- 2010
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In: NASA Planetary Data System. ; 139
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Journal article (peer-reviewed)abstract
- This data set contains the data from the Galileo dust detector system (GDDS) from start of mission through the end of mission. Included are the dust impact data, noise data, laboratory calibration data, and location and orientation of the spacecraft and instrument.
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| 37. |
- Krüger, H., et al.
(author)
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Four years of Ulysses dust data: 1996-1999
- 2001
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In: Planetary and Space Science. - 1873-5088. ; 49:13, s. 1303-1324
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Journal article (peer-reviewed)abstract
- The Ulysses spacecraft is orbiting the Sun on a highly inclined ellipse(/i=79°, perihelion distance 1.3 AU, aphelion distance 5.4 AU).Between January /1996 and December /1999 the spacecraft was beyond 3 AUfrom the Sun and crossed the ecliptic plane at aphelion in May /1998. Inthis 4-yr period 218 dust impacts were recorded with the dust detectoron board. We publish and analyse the complete data set of both raw andreduced data for particles with masses10-16-10-8g. Together with 1477 dust impactsrecorded between launch of Ulysses and the end of /1995 publishedearlier (Grün et al., Planet. Space Sci. 43 (/1995a) 971;Krüger et al., Planet. Space Sci. 47 (/1999b) 363), a data set of1695 dust impacts detected with the Ulysses sensor between October /1990and December /1999 is now available. The impact rate measured between1996 and 1999 was relatively constant with about 0.2 impacts per day.The impact direction of the majority of the impacts is compatible withparticles of interstellar origin, the rest are most likelyinterplanetary particles. The observed impact rate is compared with amodel for the flux of interstellar dust particles. The flux of particlesseveral micrometres in size is compared with the measurements of thedust instruments on board Pioneer 10 and Pioneer 11 beyond 3 AU (Humes,J. Geophys. Res. 85 /(1980) 5841). Between 3 and 5 AU, Pioneer resultspredict that Ulysses should have seen 5 times more (~10mum sized)particles than actually detected.
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| 38. |
- Krüger, H., et al.
(author)
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Three years of Galileo dust data. II. 1993-1995
- 1999
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In: Planetary and Space Science. - 1873-5088. ; 47:1-2, s. 85-106
-
Journal article (peer-reviewed)abstract
- Between January 1993 - December 1995, the Galileo spacecraft traversed the interplanetary space between Earth and Jupiter and arrived at Jupiter on 7 December 1995. The dust instrument onboard the spacecraft was operating during most of the time and data from the instrument were obtained via memory readouts which occurred at rates between twice per day and once per week. All events were classified by an onboard program into 24 categories. Noise events were usually restricted to the lowest categories (class 0). During Galileo's passage through Jupiter's radiation belts on 7 December 1995, several of the higher categories (classes 1 and 2) also show evidence for contamination by noise. The highest categories (class 3) were noise-free all the time. A relatively constant impact rate of interplanetary and interstellar (big) particles of 0.4 impacts per day was detected over the whole three-year time span. In the outer solar system (outside about 2.6 AU) they are mostly of interstellar origin, whereas in the inner solar system they are mostly interplanetary particles. Within about 1.7 AU from Jupiter intense streams of small dust particles were detected with impact rates of up to 20,000 per day whose impact directions are compatible with a Jovian origin. Two different populations of dust particles were detected in the Jovian magnetosphere: small stream particles during Galileo's approach to the planet and big particles concentrated closer to Jupiter between the Galilean satellites. Information about 2883 particles detected by the dust instrument during Galileo's six-year journey to Jupiter is now available.
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| 39. |
- Margulies, Elliott H, et al.
(author)
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Analyses of deep mammalian sequence alignments and constraint predictions for 1% of the human genome
- 2007
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In: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 17:6, s. 760-774
-
Journal article (peer-reviewed)abstract
- A key component of the ongoing ENCODE project involves rigorous comparative sequence analyses for the initially targeted 1% of the human genome. Here, we present orthologous sequence generation, alignment, and evolutionary constraint analyses of 23 mammalian species for all ENCODE targets. Alignments were generated using four different methods; comparisons of these methods reveal large-scale consistency but substantial differences in terms of small genomic rearrangements, sensitivity (sequence coverage), and specificity (alignment accuracy). We describe the quantitative and qualitative trade-offs concomitant with alignment method choice and the levels of technical error that need to be accounted for in applications that require multisequence alignments. Using the generated alignments, we identified constrained regions using three different methods. While the different constraint-detecting methods are in general agreement, there are important discrepancies relating to both the underlying alignments and the specific algorithms. However, by integrating the results across the alignments and constraint-detecting methods, we produced constraint annotations that were found to be robust based on multiple independent measures. Analyses of these annotations illustrate that most classes of experimentally annotated functional elements are enriched for constrained sequences; however, large portions of each class (with the exception of protein-coding sequences) do not overlap constrained regions. The latter elements might not be under primary sequence constraint, might not be constrained across all mammals, or might have expendable molecular functions. Conversely, 40% of the constrained sequences do not overlap any of the functional elements that have been experimentally identified. Together, these findings demonstrate and quantify how many genomic functional elements await basic molecular characterization.
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| 40. |
- Molvin, John, et al.
(author)
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Proteomic exploration of common pathophysiological pathways in diabetes and cardiovascular disease
- 2020
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In: ESC Heart Failure. - : Wiley. - 2055-5822. ; 7:6, s. 4151-4158
-
Journal article (peer-reviewed)abstract
- Aims The epidemiological association between diabetes and cardiovascular disease is well established, but the pathophysiological link is complex and multifactorial. We investigated seven proteins, previously linked to incident diabetes mellitus, and their association with cardiovascular disease and mortality. Methods and results Plasma samples from 1713 individuals from the Swedish population-based Malmo Preventive Project (mean age 67.4 +/- 6.0 years; 29.1% women) were analysed with a proximity extension assay panel. Seven proteins [scavenger receptor cysteine rich type 1 protein M130 (CD163), fatty acid-binding protein 4 (FABP4), plasminogen activator inhibitor 1 (PAI), insulin-like growth factor-binding protein 2 (IGFB2), cathepsin D (CTSD), galectin-4 (GAL4), and paraoxonase-3 (PON3)] previously shown to be associated with incident diabetes were analysed for associations with all-cause mortality (ACM), cardiovascular mortality (CVM), incident coronary events (CEs), and incident heart failure (HF). After exclusion of prevalent cases of respective outcome, proteins that met Bonferroni-corrected significance were analysed in multivariable Cox regression models. Significant associations were identified between five proteins [GAL4 (hazard ratio; 95% confidence interval: 1.17-1.41), CTSD (1.15-1.37), CD163 (1.09-1.30), IGFBP2 (1.05-1.30), and FABP4 (1.04-1.29)] and ACM and four proteins [GAL4 (1.38-1.56), CTSD (1.14-1.43), CD163 (1.09-1.36), and IGFBP2 (1.03-1.35)] with CVM. Three proteins [GAL4 (1.14-1.57), CTSD (1.12-1.50), and FABP4 (1.05-1.55)] were significantly associated with incident CE and two [GAL4 (1.03-1.54) and CTSD (1.01-1.46)] were associated with incident HF after adjusting for traditional risk factors including N-terminal pro-brain natriuretic peptide. Conclusions In a general Swedish population, four proteins previously shown to be associated with diabetes were associated with ACM and CVM. Three proteins were associated with incident CE. Finally, GAL4 and CTSD displayed novel associations with incident HF and were the only proteins associated with all outcomes.
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| 41. |
- Molvin, John, et al.
(author)
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Using a Targeted Proteomics Chip to Explore Pathophysiological Pathways for Incident Diabetes-The Malmo Preventive Project
- 2019
-
In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
-
Journal article (peer-reviewed)abstract
- Multiplex proteomic platforms provide excellent tools for investigating associations between multiple proteins and disease (e.g., diabetes) with possible prognostic, diagnostic, and therapeutic implications. In this study our aim was to explore novel pathophysiological pathways by examining 92 proteins and their association with incident diabetes in a population-based cohort (146 cases of diabetes versus 880 controls) followed over 8 years. After adjusting for traditional risk factors, we identified seven proteins associated with incident diabetes. Four proteins (Scavenger receptor cysteine rich type 1 protein M130, Fatty acid binding protein 4, Plasminogen activator inhibitor 1 and Insulin-like growth factor-binding protein 2) with a previously established association with incident diabetes and 3 proteins (Cathepsin D, Galectin-4, Paraoxonase type 3) with a novel association with incident diabetes. Galectin-4, with an increased risk of diabetes, and Paraoxonase type 3, with a decreased risk of diabetes, remained significantly associated with incident diabetes after adjusting for plasma glucose, implying a glucose independent association with diabetes.
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| 42. |
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| 43. |
- Prokopenko, Inga, et al.
(author)
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Variants in MTNR1B influence fasting glucose levels
- 2009
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:1, s. 77-81
-
Journal article (peer-reviewed)abstract
- To identify previously unknown genetic loci associated with fasting glucose concentrations, we examined the leading association signals in ten genome-wide association scans involving a total of 36,610 individuals of European descent. Variants in the gene encoding melatonin receptor 1B (MTNR1B) were consistently associated with fasting glucose across all ten studies. The strongest signal was observed at rs10830963, where each G allele (frequency 0.30 in HapMap CEU) was associated with an increase of 0.07 (95% CI = 0.06-0.08) mmol/l in fasting glucose levels (P = 3.2 x 10(-50)) and reduced beta-cell function as measured by homeostasis model assessment (HOMA-B, P = 1.1 x 10(-15)). The same allele was associated with an increased risk of type 2 diabetes (odds ratio = 1.09 (1.05-1.12), per G allele P = 3.3 x 10(-7)) in a meta-analysis of 13 case-control studies totaling 18,236 cases and 64,453 controls. Our analyses also confirm previous associations of fasting glucose with variants at the G6PC2 (rs560887, P = 1.1 x 10(-57)) and GCK (rs4607517, P = 1.0 x 10(-25)) loci.
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| 44. |
- Rahman, M, et al.
(author)
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GABA-site antagonism and pentobarbital actions do not depend on the alpha-subunit type in the recombinant rat GABA receptor.
- 2006
-
In: Acta physiologica (Oxford, England). - : Wiley. - 1748-1708 .- 1748-1716. ; 187:4, s. 479-88
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Journal article (peer-reviewed)abstract
- The roles of alpha-subunits on the gamma-aminobutyric acid (GABA)-site antagonism and pentobarbital actions were examined in rat recombinant GABA(A) receptors in Xenopus oocytes.Experiments were performed with binary and ternary GABA(A) receptors containing alpha1-, alpha4- or alpha5-subunit by the two-electrode voltage-clamp technique.The potency of GABA was significantly higher in the alpha1beta2, alpha4beta2 and alpha5beta2 receptors compared with the alpha1beta2gamma2L, alpha4beta2gamma2L and alpha5beta2gamma2L receptors. However, the alpha5beta2 receptor possessed significantly lower GABA efficacy compared with the alpha5beta2gamma2L receptor. While the gamma2-subunit was essential to the potency of GABA, its influence on the apparent GABA-site antagonism was less profound. The antagonist affinity constants (K(B)) of bicuculline inhibition and slopes of Schild plots were similar between all types of ternary and binary receptors except alpha5beta2 receptor which was not tested. The pK(B)s and IC(50)s of the GABA-site antagonism were not significantly different between the alpha1beta2gamma2L, alpha4beta2gamma2L and alpha5beta2gamma2L receptors. Bicuculline blocked pentobarbital-activated currents in a reversible and non-competitive manner with the alpha1beta2gamma2L, alpha4beta2gamma2L, and alpha5beta2gamma2L receptors, indicating an allosteric inhibition of the GABA-site. No significant difference of bicuculline potencies in inhibiting GABA- and pentobarbital-activated currents was found between the alpha1beta2gamma2L, alpha4beta2gamma2L and alpha5beta2gamma2L receptors.The GABA-site antagonism does not depend on the subtype of alpha-subunits. Similarly, pentobarbital activates ternary receptors composed of different alpha-subunits in a bicuculline-sensitive manner. The potencies of bicuculline to inhibit pentobarbital-activated currents are identical with receptors containing alpha1, alpha4 or alpha5-subunit. The alpha1beta2 and alpha4beta2 receptors possess higher GABA potencies compared with the alpha1beta2gamma2L and alpha4beta2gamma2L receptors.
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| 45. |
- Amemiya, Chris T., et al.
(author)
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The African coelacanth genome provides insights into tetrapod evolution
- 2013
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 496:7445, s. 311-316
-
Journal article (peer-reviewed)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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| 46. |
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| 47. |
- Casewell, Nicholas R, et al.
(author)
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Solenodon genome reveals convergent evolution of venom in eulipotyphlan mammals.
- 2019
-
In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 116:51, s. 25745-25755
-
Journal article (peer-reviewed)abstract
- Venom systems are key adaptations that have evolved throughout the tree of life and typically facilitate predation or defense. Despite venoms being model systems for studying a variety of evolutionary and physiological processes, many taxonomic groups remain understudied, including venomous mammals. Within the order Eulipotyphla, multiple shrew species and solenodons have oral venom systems. Despite morphological variation of their delivery systems, it remains unclear whether venom represents the ancestral state in this group or is the result of multiple independent origins. We investigated the origin and evolution of venom in eulipotyphlans by characterizing the venom system of the endangered Hispaniolan solenodon (Solenodon paradoxus). We constructed a genome to underpin proteomic identifications of solenodon venom toxins, before undertaking evolutionary analyses of those constituents, and functional assessments of the secreted venom. Our findings show that solenodon venom consists of multiple paralogous kallikrein 1 (KLK1) serine proteases, which cause hypotensive effects in vivo, and seem likely to have evolved to facilitate vertebrate prey capture. Comparative analyses provide convincing evidence that the oral venom systems of solenodons and shrews have evolved convergently, with the 4 independent origins of venom in eulipotyphlans outnumbering all other venom origins in mammals. We find that KLK1s have been independently coopted into the venom of shrews and solenodons following their divergence during the late Cretaceous, suggesting that evolutionary constraints may be acting on these genes. Consequently, our findings represent a striking example of convergent molecular evolution and demonstrate that distinct structural backgrounds can yield equivalent functions.
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| 48. |
- Cunningham, S G, et al.
(author)
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Core Standards of the EUBIROD Project. Defining a European Diabetes Data Dictionary for Clinical Audit and Healthcare Delivery.
- 2016
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In: Methods of information in medicine. - 2511-705X. ; 55:2, s. 166-76
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Journal article (peer-reviewed)abstract
- A set of core diabetes indicators were identified in a clinical review of current evidence for the EUBIROD project. In order to allow accurate comparisons of diabetes indicators, a standardised currency for data storage and aggregation was required. We aimed to define a robust European data dictionary with appropriate clinical definitions that can be used to analyse diabetes outcomes and provide the foundation for data collection from existing electronic health records for diabetes.Existing clinical datasets used by 15 partner institutions across Europe were collated and common data items analysed for consistency in terms of recording, data definition and units of measurement. Where necessary, data mappings and algorithms were specified in order to allow partners to meet the standard definitions. A series of descriptive elements were created to document metadata for each data item, including recording, consistency, completeness and quality.While datasets varied in terms of consistency, it was possible to create a common standard that could be used by all. The minimum dataset defined 53 data items that were classified according to their feasibility and validity. Mappings and standardised definitions were used to create an electronic directory for diabetes care, providing the foundation for the EUBIROD data analysis repository, also used to implement the diabetes registry and model of care for Cyprus.The development of data dictionaries and standards can be used to improve the quality and comparability of health information. A data dictionary has been developed to be compatible with other existing data sources for diabetes, within and beyond Europe.
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| 49. |
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| 50. |
- Fored, C. M., et al.
(author)
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Acetaminophen, aspirin, and chronic renal failure
- 2001
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In: New England Journal of Medicine. - Waltham, USA : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 345:25, s. 1801-1808
-
Journal article (peer-reviewed)abstract
- Background: Several epidemiologic studies have demonstrated an association between heavy consumption of nonnarcotic analgesics and the occurrence of chronic renal failure, but it is unclear which is the cause and which is the effect.Methods: In a nationwide, population-based, case-control study of early-stage chronic renal failure in Sweden, face-to-face interviews were conducted with 926 patients with newly diagnosed renal failure and 998 control subjects, of whom 918 and 980, respectively, had complete data. We used logistic-regression models to estimate the relative risks of disease-specific types of chronic renal failure associated with the use of various analgesics.Results: Aspirin and acetaminophen were used regularly by 37 percent and 25 percent, respectively, of the patients with renal failure and by 19 percent and 12 percent, respectively, of the controls. Regular use of either drug in the absence of the other was associated with an increase by a factor of 2.5 in the risk of chronic renal failure from any cause. The relative risks rose with increasing cumulative lifetime doses, rose more consistently with acetaminophen use than with aspirin use, and were increased for most disease-specific types of chronic renal failure. When we disregarded the recent use of analgesics, which could have occurred in response to antecedents of renal disease, the associations were only slightly attenuated.Conclusions: Our results are consistent with the existence of exacerbating effects of acetaminophen and aspirin on chronic renal failure. However, we cannot rule out the possibility of bias due to the triggering of analgesic consumption by predisposing conditions.
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