| 1. |
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| 2. |
- Birney, Ewan, et al.
(författare)
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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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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Tidskriftsartikel (refereegranskat)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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| 3. |
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| 4. |
- Clark, Andrew G., et al.
(författare)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Tidskriftsartikel (refereegranskat)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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| 5. |
- Wade, C. M., et al.
(författare)
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Genome Sequence, Comparative Analysis, and Population Genetics of the Domestic Horse
- 2009
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 326:5954, s. 865-867
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Tidskriftsartikel (refereegranskat)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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| 6. |
- Gretarsdottir, Solveig, et al.
(författare)
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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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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:8, s. 71-692
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Tidskriftsartikel (refereegranskat)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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| 7. |
- Shin, J. H., et al.
(författare)
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IA-2 autoantibodies in incident type I diabetes patients are associated with a polyadenylation signal polymorphism in GIMAP5
- 2007
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Ingår i: Genes Immun. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 8:6, s. 503-12
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Tidskriftsartikel (refereegranskat)abstract
- In a large case-control study of Swedish incident type I diabetes patients and controls, 0-34 years of age, we tested the hypothesis that the GIMAP5 gene, a key genetic factor for lymphopenia in spontaneous BioBreeding rat diabetes, is associated with type I diabetes; with islet autoantibodies in incident type I diabetes patients or with age at clinical onset in incident type I diabetes patients. Initial scans of allelic association were followed by more detailed logistic regression modeling that adjusted for known type I diabetes risk factors and potential confounding variables. The single nucleotide polymorphism (SNP) rs6598, located in a polyadenylation signal of GIMAP5, was associated with the presence of significant levels of IA-2 autoantibodies in the type I diabetes patients. Patients with the minor allele A of rs6598 had an increased prevalence of IA-2 autoantibody levels compared to patients without the minor allele (OR=2.2; Bonferroni-corrected P=0.003), after adjusting for age at clinical onset (P=8.0 x 10(-13)) and the numbers of HLA-DQ A1*0501-B1*0201 haplotypes (P=2.4 x 10(-5)) and DQ A1*0301-B1*0302 haplotypes (P=0.002). GIMAP5 polymorphism was not associated with type I diabetes or with GAD65 or insulin autoantibodies, ICA, or age at clinical onset in patients. These data suggest that the GIMAP5 gene is associated with islet autoimmunity in type I diabetes and add to recent findings implicating the same SNP in another autoimmune disease.
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| 8. |
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| 9. |
- Lewin, Harris A., et al.
(författare)
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The Earth BioGenome Project 2020 : Starting the clock
- 2022
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Ingår i: 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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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 10. |
- Christmas, Matthew, et al.
(författare)
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Evolutionary constraint and innovation across hundreds of placental mammals
- 2023
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 380:6643
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Tidskriftsartikel (refereegranskat)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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| 11. |
- Gruen, E., et al.
(författare)
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Ulysses Dust Detection System V3.1
- 2010
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Ingår i: NASA Planetary Data System. ; 140
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Tidskriftsartikel (refereegranskat)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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| 12. |
- Lundgren, Fredrik, et al.
(författare)
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PTFE bypass to below-knee arteries : distal vein collar or not? A prospective randomised multicentre study
- 2010
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Ingår i: European Journal of Vascular and Endovascular Surgery. - : Elsevier BV. - 1078-5884 .- 1532-2165. ; 39:6, s. 747-754
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPatency and limb salvage after synthetic bypass to the arteries below-knee are inferior to that which can be achieved with autologous vein. Use of a vein collar at the distal anastomosis has been suggested to improve patency and limb salvage, a problem that is analysed in this randomised clinical study.MethodsPatients with critical limb ischaemia undergoing polytetrafluoroethylene (PTFE) bypass to below-knee arteries were randomly either assigned a vein collar or not in two groups – bypass to the popliteal artery below-knee (femoro-popliteal below-knee (FemPopBK)) and more distal bypass (femoro-distal bypass (FemDist)). Follow-up was scheduled until amputation, death or at most 5 years, whichever event occurred first.ResultsIn the FemPopBK and in the FemDist groups, 115/202 and 72/150 were randomised to have a vein collar, respectively. Information was available for 345 of 352 randomised patients (98%).At 3 years, primary patency was 26% (95% confidence interval (CI) 18–38) with a vein collar and 43 (33–58) without a vein collar for femoro-popliteal bypass and 20 (11–38), and 17 (9–33) for femoro-distal bypass, respectively. The corresponding figures for limb salvage were 64 (54–75) and 61 (50–74) for femoro-popliteal bypass, and 59 (46–76) and 44 (32–61) for femoro-distal bypass with and without a vein collar, respectively. Log-rank-test for the whole Kaplan–Meier life table curve showed no statistically significant differences with or without vein collar primary patency: p = 0.0853, p = 0.228; secondary patency: p = 0.317, p = 0.280; limb salvage: p = 0.757, p = 0.187 for FemPopBK and FemDist, respectively. The use of a vein collar did not influence patency or limb salvage.ConclusionThis study failed to show any benefit for vein collar with PTFE bypass to a below-knee artery.
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| 13. |
- Margulies, Elliott H, et al.
(författare)
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Analyses of deep mammalian sequence alignments and constraint predictions for 1% of the human genome
- 2007
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 17:6, s. 760-774
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Tidskriftsartikel (refereegranskat)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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| 14. |
- Sedimbi, S. K., et al.
(författare)
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SUMO4 M55V polymorphism affects susceptibility to type I diabetes in HLA DR3- and DR4-positive Swedish patients
- 2007
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Ingår i: Genes Immun. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 8:6, s. 518-21
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Tidskriftsartikel (refereegranskat)abstract
- SUMO4 M55V, located in IDDM5, has been a focus for debate because of its association to type I diabetes (TIDM) in Asians but not in Caucasians. The current study aims to test the significance of M55V association to TIDM in a large cohort of Swedish Caucasians, and to test whether M55V is associated in those carrying human leukocyte antigen (HLA) class II molecules. A total of 673 TIDM patients and 535 age- and sex-matched healthy controls were included in the study. PCR-RFLP was performed to identify the genotype and allele variations. Our data suggest that SUMO4 M55V is not associated with susceptibility to TIDM by itself. When we stratified our patients and controls based on heterozygosity for HLA-DR3/DR4 and SUMO4 genotypes, we found that presence of SUMO4 GG increased further the relative risk conferred by HLA-DR3/DR4 to TIDM, whereas SUMO4 AA decreased the risk. From the current study, we conclude that SUMO4 M55V is associated with TIDM in association with high-risk HLA-DR3 and DR4, but not by itself.
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| 15. |
- Busweiler, L A D, et al.
(författare)
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International benchmarking in oesophageal and gastric cancer surgery
- 2019
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Ingår i: BJS Open. - : Oxford University Press (OUP). - 2474-9842. ; 3:1, s. 62-73
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Tidskriftsartikel (refereegranskat)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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| 16. |
- Costa, M, et al.
(författare)
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Results from an ATM-based event builder demonstrator
- 1996
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Ingår i: IEEE TRANSACTIONS ON NUCLEAR SCIENCE. - : IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. - 0018-9499. ; 43:3, s. 1814-1820
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)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.
(författare)
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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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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 43:Suppl 2, s. 2189-2189
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)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. |
- Gyllenberg, A, et al.
(författare)
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Variability in the CIITA gene interacts with HLA in multiple sclerosis.
- 2014
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Ingår i: Genes and immunity. - Stockholm : Springer Science and Business Media LLC. - 1476-5470 .- 1466-4879. ; 15, s. 162-167
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Tidskriftsartikel (refereegranskat)abstract
- The human leukocyte antigen (HLA) is the main genetic determinant of multiple sclerosis (MS) risk. Within the HLA, the class II HLA-DRB1*15:01 allele exerts a disease-promoting effect, whereas the class I HLA-A*02 allele is protective. The CIITA gene is crucial for expression of class II HLA molecules and has previously been found to associate with several autoimmune diseases, including MS and type 1 diabetes. We here performed association analyses with CIITA in 2000 MS cases and up to 6900 controls as well as interaction analysis with HLA. We find that the previously investigated single-nucleotide polymorphism rs4774 is associated with MS risk in cases carrying the HLA-DRB1*15 allele (P=0.01, odds ratio (OR): 1.21, 95% confidence interval (CI): 1.04-1.40) or the HLA-A*02 allele (P=0.01, OR: 1.33, 95% CI: 1.07-1.64) and that these associations are independent of the adjacent confirmed MS susceptibility gene CLEC16A. We also confirm interaction between rs4774 and HLA-DRB1*15:01 such that individuals carrying the risk allele for rs4774 and HLA-DRB1*15:01 have a higher than expected risk for MS. In conclusion, our findings support previous data that variability in the CIITA gene affects MS risk, but also that the effect is modulated by MS-associated HLA haplotypes. These findings further underscore the biological importance of HLA for MS risk.Genes and Immunity advance online publication, 16 January 2014; doi:10.1038/gene.2013.71.
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| 19. |
- Helgadottir, Anna, et al.
(författare)
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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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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:2, s. 217-224
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Tidskriftsartikel (refereegranskat)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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| 20. |
- Krueger, H., et al.
(författare)
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Five years of Ulysses dust data: 2000-2004
- 2006
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Ingår i: Planetary and Space Science. - : Elsevier BV. - 1873-5088 .- 0032-0633. ; 54:9-10, s. 932-956
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Tidskriftsartikel (refereegranskat)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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| 21. |
- Krüger, H., et al.
(författare)
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Three years of Ulysses dust data: 1993-1995
- 1999
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Ingår i: Planetary and Space Science. - 1873-5088. ; 47:3-4, s. 363-383
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Tidskriftsartikel (refereegranskat)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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| 22. |
- Kumagai, K., et al.
(författare)
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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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Ingår i: European Journal of Surgical Oncology. - : Elsevier BV. - 0748-7983 .- 1532-2157. ; 41:3, s. 282-294
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Forskningsöversikt (refereegranskat)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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| 23. |
- Landin-Olsson, Mona, et al.
(författare)
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Immunoreactive trypsin(Ogen) in the sera of children with recent-onset insulin-dependent diabetes and matched controls
- 1990
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Ingår i: Pancreas. - : Ovid Technologies (Wolters Kluwer Health). - 0885-3177. ; 5:3, s. 241-247
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate the exocrine pancreatic function at the time of diagnosis of insulin-dependent diabetes mellitus, we determined immunoreactive an-odal and cathodal trypsin(ogen) levels in sera from almost all children (n = 375) 0-14 years of age in Sweden in whom diabetes developed during 1 year, and in sex-, age-, and geographically matched control subjects (n = 312). The median level of anodal trypsin(ogen) was 5 (quartile range, 3-7) µg/L in children with newly diagnosed diabetes, compared with a median level of 7 (quartile range, 4-8) µg/L in control subjects (p < 0.0001). Similarly, the median level of cathodal trypsin(ogen) was 8 (quartile range, 4-10) µg/L in children with diabetes, compared with a median level of 11 (quartile range, 7-15) µg/L in control subjects (p < 0.0001). The median of the individual ratios between cathodal and anodal trypsin(ogen) was 1.4 in the diabetic patients and 1.7 in the control children (p < 0.001). In a multivariate test, however, only the decrease in cathodal trypsin(ogen) concentration was associated with diabetes. The levels of trypsin(ogen)s did not correlate with levels of islet cell antibodies, present in 81% of the diabetic children. Several mechanisms may explain our findings, for example, similar pathogenetic factors may affect both the endocrine and exocrine pancreas simultaneously, a failing local trophic stimulation by insulin on the exocrine cells may decrease the trypsinogen production, and there may be an increased elimination of trypsin(ogen) because of higher filtration through the kidneys in the hyperglycemic state.
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| 24. |
- Lindehammer, Sabina, et al.
(författare)
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Temporal trends of HLA genotype frequencies of type 1 diabetes patients in Sweden from 1986 to 2005 suggest altered risk
- 2008
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Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233. ; 45:4, s. 231-5
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to compare the frequency of human leukocyte antigen (HLA) genotypes in 1-18-year-old patients with type 1 diabetes newly diagnosed in 1986-1987 (n = 430), 1996-2000 (n = 342) and in 2003-2005 (n = 171). We tested the hypothesis that the HLA DQ genotype distribution changes over time. Swedish type 1 diabetes patients and controls were typed for HLA using polymerase chain reaction amplification and allele specific probes for DQ A1* and B1* alleles. The most common type 1 diabetes HLA DQA1*-B1*genotype 0501-0201/0301-0302 was 36% (153/430) in 1986-1987 and 37% (127/342) in 1996-2000, but decreased to 19% (33/171) in 2003-2005 (P \ 0.0001). The 0501-0201/0501-0201 genotype increased from 1% in 1986-1987 to 7% in 1996-2000 (P = 0.0047) and to 5% in 2003-2005 (P > 0.05). This study in 1-18-year-old Swedish type 1 diabetes patients supports the notion that there is a temporal change in HLA risk.
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| 25. |
- Sanjeevi, Carani B., et al.
(författare)
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The risk conferred by HLA-DR and DQ for type 1 diabetes in 0-35-year age group are different in different regions of Sweden
- 2008
-
Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. - 9781573317337 ; 1150, s. 106-11
-
Tidskriftsartikel (refereegranskat)abstract
- HLA DR4-DQ8 and DR3-DQ2 haplotypes account for 89% of newly diagnosed cases of type 1 diabetes (T1D) in Sweden. The presence of a single copy of DQ6 confers protection. The aim of the present study is to evaluate whether the risk conferred by high risk HLA DR and DQ to T1D is similar in all regions of Sweden and see whether there are any significant regional differences. The subjects comprised 799 consecutively diagnosed T1D patients and 585 age-, sex-, and geography-matched healthy controls in the age group 0-35 years. HLA typing for high-risk haplotypes was previously performed using PCR-SSOP and RFLP. The results showed that HLA DR3-DR4 gave an odds ratio of 8.14 for the whole of Sweden. However, when the study group was divided into six geographical regions, subjects from Stockholm had the highest OR, followed by those from Lund, Linköping, Gothenburg, Umeå, and Uppsala. Absolute protection was conferred by the presence of DQ6 in subjects from the Linköping region, but varied in the other regions. The frequency of DR3 and DQ2, DR4 and DQ8, DR15, and DQ6 in patients showed high linkage for each region, but were different between regions. In conclusion: The risk conferred by high-risk HLA varies in different regions for a homogenous population in Sweden. The results highlight the important role played by the various environmental factors in the precipitation of T1D.
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| 26. |
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| 27. |
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| 28. |
- Frantz, A M, et al.
(författare)
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Molecular Profiling Reveals Prognostically Significant Subtypes of Canine Lymphoma
- 2013
-
Ingår i: Veterinary pathology. - : SAGE Publications. - 0300-9858 .- 1544-2217. ; 50:4, s. 693-703
-
Tidskriftsartikel (refereegranskat)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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| 29. |
- Grun, E., et al.
(författare)
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South-North and Radial Traverses through the Interplanetary Dust Cloud
- 1997
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Ingår i: Icarus. - : Elsevier BV. - 0019-1035. ; 129:2, s. 270-288
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Tidskriftsartikel (refereegranskat)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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| 30. |
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| 31. |
- Helgadottir, Anna, et al.
(författare)
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Apolipoprotein(a) Genetic Sequence Variants Associated With Systemic Atherosclerosis and Coronary Atherosclerotic Burden But Not With Venous Thromboembolism
- 2012
-
Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 60:8, s. 722-729
-
Tidskriftsartikel (refereegranskat)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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| 32. |
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| 33. |
- Krueger, H., et al.
(författare)
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Galileo Dust Detection System V4.1
- 2010
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Ingår i: NASA Planetary Data System. ; 139
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Tidskriftsartikel (refereegranskat)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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| 34. |
- Krüger, H., et al.
(författare)
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Four years of Ulysses dust data: 1996-1999
- 2001
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Ingår i: Planetary and Space Science. - 1873-5088. ; 49:13, s. 1303-1324
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Tidskriftsartikel (refereegranskat)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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| 35. |
- Krüger, H., et al.
(författare)
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Three years of Galileo dust data. II. 1993-1995
- 1999
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Ingår i: Planetary and Space Science. - 1873-5088. ; 47:1-2, s. 85-106
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Tidskriftsartikel (refereegranskat)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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| 36. |
- Lindblad-Toh, Kerstin, et al.
(författare)
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Genome sequence, comparative analysis and haplotype structure of the domestic dog.
- 2005
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 438:7069, s. 803-19
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Tidskriftsartikel (refereegranskat)abstract
- Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.
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| 37. |
- Lundtoft, Christian, et al.
(författare)
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Strong Association of Combined Genetic Deficiencies in the Classical Complement Pathway With Risk of Systemic Lupus Erythematosus and Primary Sjogren's Syndrome
- 2022
-
Ingår i: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 74:11, s. 1842-1850
-
Tidskriftsartikel (refereegranskat)abstract
- Objective Complete genetic deficiency of the complement component C2 is a strong risk factor for monogenic systemic lupus erythematosus (SLE), but whether heterozygous C2 deficiency adds to the risk of SLE or primary Sjogren's syndrome (SS) has not been studied systematically. This study was undertaken to investigate potential associations of heterozygous C2 deficiency and C4 copy number variation with clinical manifestations in patients with SLE and patients with primary SS. Methods The presence of the common 28-bp C2 deletion rs9332736 and C4 copy number variation was examined in Scandinavian patients who had received a diagnosis of SLE (n = 958) or primary SS (n = 911) and in 2,262 healthy controls through the use of DNA sequencing. The concentration of complement proteins in plasma and classical complement function were analyzed in a subgroup of SLE patients. Results Heterozygous C2 deficiency-when present in combination with a low C4A copy number-substantially increased the risk of SLE (odds ratio [OR] 10.2 [95% confidence interval (95% CI) 3.5-37.0]) and the risk of primary SS (OR 13.0 [95% CI 4.5-48.4]) when compared to individuals with 2 C4A copies and normal C2. For patients heterozygous for rs9332736 with 1 C4A copy, the median age at diagnosis was 7 years earlier in patients with SLE and 12 years earlier in patients with primary SS when compared to patients with normal C2. Reduced C2 levels in plasma (P = 2 x 10(-9)) and impaired function of the classical complement pathway (P = 0.03) were detected in SLE patients with heterozygous C2 deficiency. Finally, in a primary SS patient homozygous for C2 deficiency, we observed low levels of anti-Scl-70, which suggests a risk of developing systemic sclerosis or potential overlap between primary SS and other systemic autoimmune diseases. Conclusion We demonstrate that a genetic pattern involving partial deficiencies of C2 and C4A in the classical complement pathway is a strong risk factor for SLE and for primary SS. Our results emphasize the central role of the complement system in the pathogenesis of both SLE and primary SS.
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| 38. |
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| 39. |
- Prokopenko, Inga, et al.
(författare)
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Variants in MTNR1B influence fasting glucose levels
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:1, s. 77-81
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Tidskriftsartikel (refereegranskat)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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| 40. |
- Sun, Chengjun, et al.
(författare)
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CRYAB-650 C>G (rs2234702) affects susceptibility to type 1 diabetes and IAA-positivity in Swedish population
- 2012
-
Ingår i: Human Immunology. - : Elsevier. - 0198-8859 .- 1879-1166. ; 73:7, s. 759-766
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Single nucleotide polymorphisms (SNPs) in the promoter region of CRYAB gene have been associated with in multiple sclerosis. CRYAB gene, which encodes alpha B-crystallin (a member of small heat shock protein), was reported as a potential autoimmune target. In this study we investigated whether SNPs in the promoter region of CRYAB gene were also important in the etiology of Type 1 diabetes (T1D).METHODS: Genotyping of SNPs in the promoter region of CRYAB gene was performed in a Swedish cohort containing 444 T1D patients and 350 healthy controls. Three SNPs were included in this study: CRYAB-652 A>G (rs762550), -650 C>G (rs2234702) and -249 C > G (rs14133). Two SNPs (CRYAB-652 and -650) were not included in previous genome wide association studies.RESULTS: CRYAB-650 (rs2234702)*C allele was significantly more frequent in patients than in controls (OR = 1.48, Pc = 0.03). CRYAB-650*C allele was associated with IAA positivity (OR = 8.17, Pc < 0.0001) and IA-2A positivity (OR = 2.14, Pc = 0.005) in T1D patients. This association with IAA was amplified by high-risk HLA carrier state (OR = 10.6, P < 0.0001). No association was found between CRYAB-650 and other autoantibody positivity (GADA and ICA). CRYAB haplotypes were also associated with IAA and IA-2A positivity (highest OR = 2.07 and 2.11, respectively), these associations remain in high HLA-risk T1D patients.CONCLUSIONS: CRYAB-650 was associated with T1D in the Swedish cohort we studied. CRYAB-650*C allele might confers susceptibility to the development of T1D. CRYAB-650 was also associated with the development of IAA-positivity in T1D patients, especially in those carrying T1D high-risk HLA haplotypes.
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| 41. |
- van den Berg, L, et al.
(författare)
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Evaluation of the serotonergic genes htr1A, htr1B, htr2A, and slc6A4 in aggressive behavior of golden retriever dogs
- 2008
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Ingår i: Behavior Genetics. - : Springer Science and Business Media LLC. - 0001-8244 .- 1573-3297. ; 38:1, s. 55-66
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Tidskriftsartikel (refereegranskat)abstract
- Aggressive behavior displays a high heritability in our study group of Golden Retriever dogs. Alterations in brain serotonin metabolism have been described in aggressive dogs before. Here, we evaluate whether four genes of the canine serotonergic system, coding for the serotonin receptors 1A, 1B, and 2A, and the serotonin transporter, could play a major role in aggression in Golden Retrievers. We performed mutation screens, linkage analysis, an association study, and a quantitative genetic analysis. There was no systematic difference between the coding DNA sequence of the candidate genes in aggressive and non-aggressive Golden Retrievers. An affecteds-only parametric linkage analysis revealed no strong major locus effect on human-directed aggression related to the candidate genes. An analysis of 41 single nucleotide polymorphisms (SNPs) in the 1 Mb regions flanking the genes in 49 unrelated human-directed aggressive and 49 unrelated non-aggressive dogs did not show association of SNP alleles, genotypes, or haplotypes with aggression at the candidate loci. We completed our analyses with a study of the effect of variation in the candidate genes on a collection of aggression-related phenotypic measures. The effects of the candidate gene haplotypes were estimated using the Restricted Maximum Likelihood method, with the haplotypes included as fixed effects in a linear animal model. We observed no effect of the candidate gene haplotypes on a range of aggression-related phenotypes, thus extending our conclusions to several types of aggressive behavior. We conclude that it is unlikely that these genes play a major role in the variation in aggression in the Golden Retrievers that we studied. Smaller phenotypic effects of these loci could not be ruled out with our sample size.
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| 42. |
- Amemiya, Chris T., et al.
(författare)
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The African coelacanth genome provides insights into tetrapod evolution
- 2013
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 496:7445, s. 311-316
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Tidskriftsartikel (refereegranskat)abstract
- The discovery of a living coelacanth specimen in 1938 was remarkable, as this lineage of lobe-finned fish was thought to have become extinct 70 million years ago. The modern coelacanth looks remarkably similar to many of its ancient relatives, and its evolutionary proximity to our own fish ancestors provides a glimpse of the fish that first walked on land. Here we report the genome sequence of the African coelacanth, Latimeria chalumnae. Through a phylogenomic analysis, we conclude that the lungfish, and not the coelacanth, is the closest living relative of tetrapods. Coelacanth protein-coding genes are significantly more slowly evolving than those of tetrapods, unlike other genomic features. Analyses of changes in genes and regulatory elements during the vertebrate adaptation to land highlight genes involved in immunity, nitrogen excretion and the development of fins, tail, ear, eye, brain and olfaction. Functional assays of enhancers involved in the fin-to-limb transition and in the emergence of extra-embryonic tissues show the importance of the coelacanth genome as a blueprint for understanding tetrapod evolution.
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| 43. |
- Casewell, Nicholas R, et al.
(författare)
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Solenodon genome reveals convergent evolution of venom in eulipotyphlan mammals.
- 2019
-
Ingår i: 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
-
Tidskriftsartikel (refereegranskat)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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| 44. |
- Fored, C. M., et al.
(författare)
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Acetaminophen, aspirin, and chronic renal failure
- 2001
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Ingår i: New England Journal of Medicine. - Waltham, USA : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 345:25, s. 1801-1808
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Tidskriftsartikel (refereegranskat)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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| 45. |
- Gopakumar, Geethanjali, 1992-, et al.
(författare)
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X-ray Induced Fragmentation of Protonated Cystine
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Protein structure determination using high-intensity X-ray sources induces damage in the protein. Disulfide bridges, formed between two cysteine amino acid residues stabilize the protein structure. Owing to the higher absorption cross-section of sulfur for X-ray photons, and a large number of electrons released from sulfur atoms, these disulfide bridges are hot spots for a higher level of noise in structural studies. But it is yet to be understood how exactly the damage occurs through the interaction of the disulfide bridges with photons. Here we study the fragmentation of protonated cystine in the gas phase, which is the dimer of cysteine, by irradiation with X-rays across the sulfur L-edge using an electrospray ionization source (ESI) in combination with an ion trap. This is complemented with the calculation of the sulfur NEXAFS spectrum on the level of Restricted Open-Shell Configuration Interaction (ROCIS) and Density Functional Theory (DFT) calculations for molecular orbital visualization as well as Molecular Dynamics (MD) simulations for the fragmentation of triply charged cystine ions. We have deduced a possible pathway of fragmentation upon excitation and ionization of S 2p electrons by combining the experiments and simulations. The disulfide bridge breaks for resonant excitation at lower energies but remains intact upon higher energy resonant excitation and upon ionization of S 2p. The larger fragments formed subsequently break into smaller fragments.
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| 46. |
- Grün, E., et al.
(författare)
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Dust Measurements During Galileo's Approach to Jupiter and Io Encounter
- 1996
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 274:5286, s. 399-401
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Tidskriftsartikel (refereegranskat)abstract
- About a hundred dust impacts per day were detected during the first week in December 1995 by Galileo during its approach to Jupiter. These impacts were caused by submicrometer-sized particles that were just above the detection limit. After the closest approach to Io on 7 December, impacts of these small particles ceased. This effect is expected for dust grains emitted from Io that exit the field of view of the instrument after the flyby. The impact rate of bigger micrometer-sized dust grains continued to increase toward Jupiter. These dust particles are in orbit about Jupiter or are interplanetary grains that are gravitationally concentrated near Jupiter.
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| 47. |
- Grün, E., et al.
(författare)
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Dust measurements in the Jovian magnetosphere
- 1997
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Ingår i: Geophysical Research Letters. - 1944-8007. ; 24:17, s. 2171-2174
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Tidskriftsartikel (refereegranskat)abstract
- Dust measurements have been obtained with the dust detector onboard the Galileo spacecraft inside a distance of about 60RJ from Jupiter (Jupiter radius, RJ = 71,492 km) during two periods of about 8 days around Galileo's closest approaches to Ganymede on 27 June and on 6 Sept 1996. The impact rate of submicrometer-sized particles fluctuated by a factor of several hundred with a period of about 10 hours, implying that their trajectories are strongly affected by the interaction with the Jovian magnetic field. Concentrations of small dust impacts were detected at the times of Ganymede closest approaches that could be secondary ejecta particles generated upon impact of other particles onto Ganymede's surface. Micrometer-sized dust particles, which could be on bound orbits about Jupiter, are concentrated in the inner Jovian system inside about 20RJ from Jupiter.
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| 48. |
- Grün, E., et al.
(författare)
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Galileo observes electromagnetically coupled dust in the Jovian magnetosphere
- 1998
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Ingår i: Journal of Geophysical Research. - 2156-2202. ; 103:E9, s. 20011-20022
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Tidskriftsartikel (refereegranskat)abstract
- Measurements of dust coupled to the Jovian magnetosphere have been obtained with the dust detector on board the Galileo spacecraft. We report on data obtained during the first four orbits about Jupiter that had flybys of the Galilean satellites: Ganymede (orbits 1 and 2), Callisto (orbit 3), and Europa (orbit 4). The most prominent features observed are highly time variable dust streams recorded throughout the Jovian system. The impact rate varied by up to 2 orders of magnitude with a 5 and 10 hour periodicity, which shows a correlation with Galileo's position relative to the Jovian magnetic field. Around 20 RJ (Jupiter radius, RJ=71, 492 km) in bound a dip in the impact rate has been found consistently. At the same times, reversals by 180° in impact direction occurred. This behavior can be qualitatively explained by strong coupling of nanometer-sized dust to the Jovian magnetic field. At times of satellite flybys, enhanced rates of dust impacts have been observed, which suggests that all Galilean satellites are sources of ejecta particles. Inside about 20 RJ impacts of micrometer-sized particles have been recorded that could be particles on bound orbits about Jupiter.
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| 49. |
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| 50. |
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