| 1. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 2. |
- Cossarizza, A., et al.
(författare)
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Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)
- 2019
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Ingår i: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 49:10, s. 1457-1973
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Tidskriftsartikel (refereegranskat)abstract
- These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.
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| 3. |
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| 5. |
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| 6. |
- Östling, Jörgen, et al.
(författare)
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IL-17-high asthma with features of a psoriasis immunophenotype
- 2019
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 144:5, s. 1198-1213
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Tidskriftsartikel (refereegranskat)abstract
- Background: The role of IL-17 immunity is well established in patients with inflammatory diseases, such as psoriasis and inflammatory bowel disease, but not in asthmatic patients, in whom further study is required.Objective: We sought to undertake a deep phenotyping study of asthmatic patients with upregulated IL-17 immunity.Methods: Whole-genome transcriptomic analysis was performed by using epithelial brushings, bronchial biopsy specimens (91 asthmatic patients and 46 healthy control subjects), and whole blood samples (n = 498) from the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) cohort. Gene signatures induced in vitro by IL-17 and IL-13 in bronchial epithelial cells were used to identify patients with IL-17–high and IL-13–high asthma phenotypes.Results: Twenty-two of 91 patients were identified with IL-17, and 9 patients were identified with IL-13 gene signatures. The patients with IL-17–high asthma were characterized by risk of frequent exacerbations, airway (sputum and mucosal) neutrophilia, decreased lung microbiota diversity, and urinary biomarker evidence of activation of the thromboxane B2 pathway. In pathway analysis the differentially expressed genes in patients with IL-17-high asthma were shared with those reported as altered in psoriasis lesions and included genes regulating epithelial barrier function and defense mechanisms, such as IL1B, IL6, IL8, and β-defensin.Conclusion: The IL-17–high asthma phenotype, characterized by bronchial epithelial dysfunction and upregulated antimicrobial and inflammatory response, resembles the immunophenotype of psoriasis, including activation of the thromboxane B2 pathway, which should be considered a biomarker for this phenotype in further studies, including clinical trials targeting IL-17.
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| 7. |
- Elsik, Christine G., et al.
(författare)
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The Genome Sequence of Taurine Cattle : A Window to Ruminant Biology and Evolution
- 2009
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 324:5926, s. 522-528
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Tidskriftsartikel (refereegranskat)abstract
- To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.
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| 8. |
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| 9. |
- Horvath, I., et al.
(författare)
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A European Respiratory Society technical standard: exhaled biomarkers in lung disease
- 2017
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 49:4
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Tidskriftsartikel (refereegranskat)abstract
- Breath tests cover the fraction of nitric oxide in expired gas (FeNO), volatile organic compounds (VOCs), variables in exhaled breath condensate (EBC) and other measurements. For EBC and for FeNO, official recommendations for standardised procedures are more than 10 years old and there is none for exhaled VOCs and particles. The aim of this document is to provide technical standards and recommendations for sample collection and analytic approaches and to highlight future research priorities in the field. For EBC and FeNO, new developments and advances in technology have been evaluated in the current document. This report is not intended to provide clinical guidance on disease diagnosis and management. Clinicians and researchers with expertise in exhaled biomarkers were invited to participate. Published studies regarding methodology of breath tests were selected, discussed and evaluated in a consensus-based manner by the Task Force members. Recommendations for standardisation of sampling, analysing and reporting of data and suggestions for research to cover gaps in the evidence have been created and summarised. Application of breath biomarker measurement in a standardised manner will provide comparable results, thereby facilitating the potential use of these biomarkers in clinical practice.
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| 10. |
- Mallorquin, M., et al.
(författare)
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TOI-1801 b: A temperate mini-Neptune around a young M0.5 dwarf
- 2023
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 680
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Tidskriftsartikel (refereegranskat)abstract
- We report the discovery, mass, and radius determination of TOI-1801 b, a temperate mini-Neptune around a young M dwarf. TOI-1801 b was observed in TESS sectors 22 and 49, and the alert that this was a TESS planet candidate with a period of 21.3 days went out in April 2020. However, ground-based follow-up observations, including seeing-limited photometry in and outside transit together with precise radial velocity (RV) measurements with CARMENES and HIRES revealed that the true period of the planet is 10.6 days. These observations also allowed us to retrieve a mass of 5.74 +/- 1.46 M-circle plus, which together with a radius of 2.08 +/- 0.12 R-circle plus, means that TOI-1801 b is most probably composed of water and rock, with an upper limit of 2% by mass of H-2 in its atmosphere. The stellar rotation period of 16 days is readily detectable in our RV time series and in the ground-based photometry. We derived a likely age of 600-800 Myr for the parent star TOI-1801, which means that TOI-1801 b is the least massive young mini-Neptune with precise mass and radius determinations. Our results suggest that if TOI-1801 b had a larger atmosphere in the past, it must have been removed by some evolutionary mechanism on timescales shorter than 1 Gyr.
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| 11. |
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| 12. |
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| 13. |
- Baldsiefen, G, et al.
(författare)
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Shears bands in Pb-193
- 1996
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 54:3, s. 1106-1116
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Tidskriftsartikel (refereegranskat)abstract
- Four bands of enhanced dipole transitions, with weak crossovers, have been observed in Pb-195. Three of these bands are connected to the spherical levels. in addition, the spherical level scheme has been extended. The nuclear spectroscopy was done with the early implementation of GAMMASPHERE and HERA arrays of Get detectors. The nucleus Pb-193 was populated in the Yb-174(Mg-24,5n) reaction at beam energies of 129, 131, and 134 MeV. The experimental results are compared to tilted-axis cranking calculations. The systematical behavior of the dipole bands in the heavier odd-A Pb isotopes, Pb-195,Pb-197,Pb-199,Pb-201, is also discussed.
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| 14. |
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| 15. |
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| 16. |
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| 17. |
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| 18. |
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| 19. |
- Abdel-Aziz, MI, et al.
(författare)
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A System Pharmacology Multi-Omics Approach toward Uncontrolled Pediatric Asthma
- 2021
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Ingår i: Journal of personalized medicine. - : MDPI AG. - 2075-4426. ; 11:6
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Tidskriftsartikel (refereegranskat)abstract
- There is a clinical need to identify children with poor asthma control as early as possible, to optimize treatment and/or to find therapeutic alternatives. Here, we present the “Systems Pharmacology Approach to Uncontrolled Pediatric Asthma” (SysPharmPediA) study, which aims to establish a pediatric cohort of moderate-to-severe uncontrolled and controlled patients with asthma, to investigate pathophysiological mechanisms underlying uncontrolled moderate-to-severe asthma in children on maintenance treatment, using a multi-omics systems medicine approach. In this multicenter observational case–control study, moderate-to-severe asthmatic children (age; 6–17 years) were included from four European countries (Netherlands, Germany, Spain, and Slovenia). Subjects were classified based on asthma control and number of exacerbations. Demographics, current and past patient/family history, and clinical characteristics were collected. In addition, systems-wide omics layers, including epi(genomics), transcriptomics, microbiome, proteomics, and metabolomics were evaluated from multiple samples. In all, 145 children were included in this cohort, 91 with uncontrolled (median age = 12 years, 43% females) and 54 with controlled asthma (median age = 11.7 years, 37% females). The two groups did not show statistically significant differences in age, sex, and body mass index z-score distribution. Comprehensive information and diverse noninvasive biosampling procedures for various omics analyses will provide the opportunity to delineate underlying pathophysiological mechanisms of moderate-to-severe uncontrolled pediatric asthma. This eventually might reveal novel biomarkers, which could potentially be used for noninvasive personalized diagnostics and/or treatment.
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| 20. |
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| 21. |
- Brinkman, D. J., et al.
(författare)
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Essential Competencies in Prescribing: A First European Cross-Sectional Study Among 895 Final-Year Medical Students
- 2017
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Ingår i: Clinical Pharmacology and Therapeutics. - : WILEY-BLACKWELL. - 0009-9236 .- 1532-6535. ; 101:2, s. 281-289
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Tidskriftsartikel (refereegranskat)abstract
- European medical students should have acquired adequate prescribing competencies before graduation, but it is not known whether this is the case. In this international multicenter study, we evaluated the essential knowledge, skills, and attitudes in clinical pharmacology and therapeutics (CPT) of final-year medical students across Europe. In a cross-sectional design, 26 medical schools from 17 European countries were asked to administer a standardized assessment and questionnaire to 50 final-year students. Although there were differences between schools, our results show an overall lack of essential prescribing competencies among final-year students in Europe. Students had a poor knowledge of drug interactions and contraindications, and chose inappropriate therapies for common diseases or made prescribing errors. Our results suggest that undergraduate teaching in CPT is inadequate in many European schools, leading to incompetent prescribers and potentially unsafe patient care. A European core curriculum with clear learning outcomes and assessments should be urgently developed.
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| 22. |
- Brinkman, M J, et al.
(författare)
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Decay from a superdeformed band in Pb-194
- 1996
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 53:4, s. R1461-R1464
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Tidskriftsartikel (refereegranskat)abstract
- Three experiments using the (174) Yb(Mg-25,5n)Pb-194 reaction have been undertaken at the Early Implementation of Gammasphere to study the decay of known superdeformed states in Pb-194. A single discrete transition with an energy of 2.746(2) MeV carrying 6(2)% of the full superdeformed band intensity has been identified. A discussion of our results and the assignment of the 2.746-MeV transition as a discrete gamma ray directly connecting the superdeformed 8(+) and low-lying 6(+) levels will be presented.
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| 23. |
- Brinkman, P, et al.
(författare)
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Exhaled volatile organic compounds as markers for medication use in asthma
- 2020
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Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 55:2
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Tidskriftsartikel (refereegranskat)abstract
- Asthma is a heterogeneous condition, characterised by chronic inflammation of the airways, typically managed with inhaled bronchodilators and corticosteroids. In the case of uncontrolled asthma, oral corticosteroids (OCSs) are often prescribed. Good adherence and inhalation technique are associated with improved outcomes; however, it is difficult to monitor appropriate drug intake and effectiveness in individual patients. Exhaled breath contains thousands of volatile organic compounds (VOCs) that reflect changes in the body's chemistry and may be useful for monitoring drug pharmacokinetics/pharmacodynamics. We aimed to investigate the association of exhaled VOCs in severe asthma patients from the U-BIOPRED cohort (by gas chromatography coupled with time-of-flight mass spectrometry) with urinary levels of salbutamol and OCSs (by liquid chromatography coupled with high-resolution mass spectrometry).MethodsSamples were collected at baseline and after 12–18 months of follow-up. Statistical analysis was based on univariate and multivariate modelling, followed by area under the receiver operating characteristic curve (AUC) calculation. Results were verified through longitudinal replication and independent validation.ResultsData were available for 78 patients (baseline n=48, replication n=30 and validation n=30). Baseline AUC values were 82.1% (95% CI 70.4–93.9%) for salbutamol and 78.8% (95% CI 65.8–91.8%) for OCS. These outcomes could be adequately replicated and validated. Additional regression analysis between qualified exhaled VOCs and urinary concentrations of salbutamol and prednisone showed statistically significant correlations (p<0.01).ConclusionWe have linked exhaled VOCs to urinary detection of salbutamol and OCSs. This merits further development of breathomics into a point-of-care tool for therapeutic drug monitoring.
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| 24. |
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| 25. |
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| 26. |
- CLARK, RM, et al.
(författare)
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A PAIR OF IDENTICAL SUPERDEFORMED BANDS IN ND-136
- 1995
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Ingår i: Physics Letters B. - 0370-2693 .- 1873-2445. ; 343:1-4, s. 59-63
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Tidskriftsartikel (refereegranskat)abstract
- High-spin states in Nd-136 were populated via the Mo-100(Ar-40, 4n) reaction at beam energies of 176 and 182 MeV, and resulting gamma-rays were detected using the GAMMASPHERE spectrometer. Analysis of the data has revealed the existence of an excited superdeformed (SD) band in Nd-136. Th, yrast SD band in Nd-136 has been extended by the addition of four (possibly five) transitions at high frequency. The new band displays the remarkable property of having transition energies identical (to within +/- 1 keV) to those of the half-points of the yrast SD band of Nd-136. Possible explanations in terms of cranked Woods-Saxon single-particle calculations are discussed.
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| 27. |
- Clark, R M, et al.
(författare)
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Superdeformation in bismuth
- 1996
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 53:1, s. 117-123
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Tidskriftsartikel (refereegranskat)abstract
- High angular momentum states in Bi-195-197 are populated in two reactions: W-183(F-19,xn)Bi-202-x and Ta-181(Ne-20,xn)Bi-201-x at beam energies of 108 and 123 MeV, respectively. Gamma rays were detected using the Gammasphere array. Three weakly populated rotational sequences have been found. They each have properties characteristic of other superdeformed bands in this mass region. On the basis of cross-bombardment information we believe that one band belongs to each of Bi-195, Bi-196, and Bi-197. The properties of the bands in the odd-Bi nuclei are best reproduced if the odd proton occupies the favored signature of the [651]1/2 orbital, while the band in Bi-196 has this same proton configuration coupled to an additional N=7 (j(15/2)) neutron. The relative behavior of the J((2)) moments of inertia can be qualitatively understood in terms of Pauli-blocking effects.
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| 28. |
- DELEPLANQUE, MA, et al.
(författare)
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LOW-SPIN TERMINATION OF THE SUPERDEFORMED BAND IN ND-135
- 1995
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 52:5, s. R2302-R2305
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Tidskriftsartikel (refereegranskat)abstract
- The decay of the superdeformed (SD) band in Nd-135 was studied with the early implementation of gamma-sphere. The results suggest that the SD band ''terminates'' at spin 25/2. This termination is explained by a change of the SD minimum toward a triaxial lower deformation. Ultimate cranker calculations with the i(13/2) orbital occupied relate this change to a shift of a proton and neutron pair out of deformation-driving Nilsson orbitals. This is a completely new and unexpected mechanism for the decay of SD bands.
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| 29. |
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| 30. |
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| 31. |
- Korytár, P, et al.
(författare)
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Separation of seventeen 2,3,7,8-substituted polychlorinated dibenzo-p-dioxins and dibenzofurans and 12 dioxin-like polychlorinated biphenyls by comprehensive two-dimensional gas chromatography with electron-capture detection
- 2004
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Ingår i: Journal of Chromatography A. - Amsterdam : Elsevier. - 0021-9673 .- 1873-3778. ; 1038:1-2, s. 189-199
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Tidskriftsartikel (refereegranskat)abstract
- Comprehensive two-dimensional gas chromatography (GC×GC) with electron-capture detection (ECD) has been optimized for the separation of seventeen 2,3,7,8-substituted polychlorinated dibenzo-p-dioxins and dibenzofurans and 12 dioxin-like polychlorinated biphenyls, with emphasis on the selection of the first- and second-dimension, commercially available, columns. When eight second-dimension columns were subsequently combined with a 100% methylpolysiloxane stationary phase (DB-1) in the first dimension to create orthogonal conditions, a complete separation of all congeners with different TEF values was obtained with two column combinations, DB-1 × VF-23 and DB-1 × LC-50. When other types of first-dimension columns were used (and orthogonality was partly sacrificed), a DB-XLB column combined with 007-65HT, VF-23 and LC-50 was found to provide a complete separation of all 29 priority congeners. Next, the potential of these three column combinations for real-life analysis was preliminarily studied. With a spiked and fractionated milk extract, DB-XLB × LC-50 was found to be the most powerful column combination, because of the good separation of the 29 priority congeners from each other as well as from the matrix constituents. Quantitative performance (close to three-order linearity; LODs, 30–150 fg injected; R.S.D.s, 1.5–6.5% (n=10)) was satisfactory.
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| 32. |
- Nordborg, Mikaela, et al.
(författare)
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Phototoxic effects of two common marine fuels on the settlement success of the coral Acropora tenuis
- 2018
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Coral reefs are at risk of exposure to petroleum hydrocarbons from shipping spills and uncontrolled discharges during extraction. The toxicity of petroleum hydrocarbons can substantially increase in the presence of ultraviolet radiation (UVR), therefore spills in shallow coral reef environments may be particularly hazardous to reef species. Here we investigated the sensitivity of coral larvae (Acropora tenuis) to dissolved hydrocarbons from heavy fuel oil (HFO) and diesel in the absence and presence of UVR. Larval settlement success decreased with increasing concentrations of dissolved HFO, and co-exposure to UVR doubled the toxicity: 50% effect concentrations (EC50) decreased from 96 (-UVR) to 51 (+UVR) total petroleum aromatic hydrocarbons (TPAH). Toxic thresholds for HFO were similar to concentrations reported during marine spills: EC(10)s of 24 (-UVR) and 15 (+UVR) mu g l(-1). While less toxic, diesel also reduced settlement and exhibited phototoxicity: EC(10)s of 122 (+UVR) and 302 (-UVR) mu g l(-1). This study demonstrates that the presence of UVR increases the hazard posed by oil pollution to tropical, shallow-water coral reefs. Further research on the effects of oils in the presence of UVR is needed to improve the environmental relevance of risk assessments and ensure appropriate protection for shallow reef environments against oil pollution.
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| 33. |
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| 34. |
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| 35. |
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| 36. |
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| 37. |
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| 38. |
- BERNSTEIN, LA, et al.
(författare)
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ONSET OF COLLECTIVITY IN NEUTRON-DEFICIENT PO-196,PO-198
- 1995
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 52:2, s. 621-627
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Tidskriftsartikel (refereegranskat)abstract
- We have studied via in-beam gamma-ray spectroscopy Po-196 and Po-198, which are the first neutron-deficient Po isotopes to exhibit a collective low-lying structure. The ratios of yrast state energies and the E2 branching ratios of transitions from non-yrast to yrast states are indicative of a low-lying vibrational structure. The onset of collective motion in these isotopes can be attributed to the opening of the neutron i(13/2) orbital at N approximate to 112 and the resulting large overlap between the two valence protons in the h(9/2) orbital and the valence neutrons in the i(13/2) orbital.
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| 39. |
- Boot, Iris W. A., et al.
(författare)
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Dietary B group vitamin intake and the bladder cancer risk : a pooled analysis of prospective cohort studies
- 2022
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Ingår i: European Journal of Nutrition. - : Springer Nature. - 1436-6207 .- 1436-6215. ; 61:5, s. 2397-2416
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Diet may play an essential role in the aetiology of bladder cancer (BC). The B group complex vitamins involve diverse biological functions that could be influential in cancer prevention. The aim of the present study was to investigate the association between various components of the B group vitamin complex and BC risk.Methods: Dietary data were pooled from four cohort studies. Food item intake was converted to daily intakes of B group vitamins and pooled multivariate hazard ratios (HRs), with corresponding 95% confidence intervals (CIs), were obtained using Cox-regression models. Dose–response relationships were examined using a nonparametric test for trend.Results: In total, 2915 BC cases and 530,012 non-cases were included in the analyses. The present study showed an increased BC risk for moderate intake of vitamin B1 (HRB1: 1.13, 95% CI: 1.00–1.20). In men, moderate intake of the vitamins B1, B2, energy-related vitamins and high intake of vitamin B1 were associated with an increased BC risk (HR (95% CI): 1.13 (1.02–1.26), 1.14 (1.02–1.26), 1.13 (1.02–1.26; 1.13 (1.02–1.26), respectively). In women, high intake of all vitamins and vitamin combinations, except for the entire complex, showed an inverse association (HR (95% CI): 0.80 (0.67–0.97), 0.83 (0.70–1.00); 0.77 (0.63–0.93), 0.73 (0.61–0.88), 0.82 (0.68–0.99), 0.79 (0.66–0.95), 0.80 (0.66–0.96), 0.74 (0.62–0.89), 0.76 (0.63–0.92), respectively). Dose–response analyses showed an increased BC risk for higher intake of vitamin B1 and B12.Conclusion: Our findings highlight the importance of future research on the food sources of B group vitamins in the context of the overall and sex-stratified diet.
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| 40. |
- Brinkman, D. M., et al.
(författare)
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Autologous stem cell transplantation in children with severe progressive systemic or polyarticular juvenile idiopathic arthritis: long-term follow-up of a prospective clinical trial
- 2007
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Ingår i: Arthritis Rheum. - : Wiley. - 0004-3591. ; 56:7, s. 2410-21
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To assess the safety and efficacy of intensive immunosuppression followed by T cell-depleted autologous hematopoietic stem cell transplantation (ASCT) for induction of disease remission in children with refractory progressive juvenile idiopathic arthritis (JIA). METHODS: Twenty-two patients with progressive refractory JIA were followed up over a median period of 80 months after pretreatment with intensive immunosuppression followed by ASCT in a multicenter, prospective, phase II clinical trial. Hematopoietic stem cells were harvested from the patients' bone marrow, depleted of T cells, and kept frozen until used for ASCT. Pretreatment of patients consisted of a combination of antithymocyte globulin, cyclophosphamide, and low-dose total body irradiation. Patients were followed up for ASCT-related complications, recovery of hematologic and immune system parameters, and disease outcomes. RESULTS: Reconstitution of hematologic values to normal range was rapid. Recovery of immune system parameters, especially normalization of CD4+, CD45RA+ naive T cells, was delayed, occurring at >/=6 months after ASCT. The prolonged period of immune deficiency resulted in a large number of viral infections and may have contributed to the development of macrophage activation syndrome (MAS), leading to death, in 2 patients. After ASCT, 8 of the 20 evaluable patients reached complete clinical remission of their JIA, 7 were partial responders, and 5 experienced a relapse of their disease (occurring 7 years after ASCT in 1 patient). Later during followup, 2 of the patients whose disease relapsed died from infections that developed after restarting immunosuppressive medication. CONCLUSION: Intensive immunosuppression followed by ASCT resulted in sustained complete remission or marked improvement in 15 of 22 patients with progressive refractory JIA. The procedure, however, is associated with significant morbidity and risk of mortality due to prolonged and severe depression of T cell immunity. After fatal complications due to MAS were observed in some patients, the protocol was amended in 1999, to ensure less profound depletion of T cells, better control of systemic disease before transplantation, antiviral prophylaxis after transplantation, and slow tapering of corticosteroids. Following these protocol modifications, no additional ASCT-related deaths were observed among the 11 patients who received the modified treatment.
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| 41. |
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| 42. |
- Cederwall, Bo, et al.
(författare)
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MEASUREMENT OF ULTRA-FAST GAMMA-RAY TRANSITIONS FROM HEAVY-ION COMPOUND NUCLEUS REACTIONS
- 1995
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - 0168-9002 .- 1872-9576. ; 354:2-3, s. 591-594
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Tidskriftsartikel (refereegranskat)abstract
- A method for correcting target-thickness-induced Doppler broadening in gamma-ray spectra from weakly populated, very short-lived (femtosecond) states is presented. The method is illustrated by an analysis of superdeformed transitions in Dy-152,Dy-153 for which the validity of the procedure could be verified consistently from previous lifetime measurements in Dy-152. Furthermore, estimates of the superdeformed lifetimes, previously not measured in Dy-153, are obtained.
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| 43. |
- Cederwall, Bo, et al.
(författare)
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NEW FEATURES OF SUPERDEFORMED BANDS IN HG-194
- 1994
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 72:20, s. 3150-3153
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Tidskriftsartikel (refereegranskat)abstract
- Two new features of superdeformed (SD) bands in the A almost-equal-to 190 region emerge from a study of Hg-194 with the Gammasphere detector array. A decrease of the dynamic moment of inertia is observed for rotational frequencies HBARomega greater-than-or-equal-to 0.4 MeV, confirming long standing expectations based on mean field calculations with pairing. Evidence for a small staggering in the SD transition energies is also observed, suggesting the presence of terms with fourfold symmetry in the SD Hamiltonian.
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| 44. |
- Cederwall, Bo, et al.
(författare)
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NEW OBLATE BAND IN HG-196 WITH QUENCHED M1 STRENGTH
- 1993
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 47:6, s. R2443-R2446
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Tidskriftsartikel (refereegranskat)abstract
- High-spin states in the nucleUs Hg-196 were populated in the reaction (Os(Be,5n))-Os-192 at a beam energy of 65 MeV. A regular rotational-like DELTAI = 1 band has been observed up to an excitation energy of E* almost-equal-to 8.7 MeV and spin I almost-equal-to 30hBAR. This is the second observation of a band of this character in a mercury isotope. The experimental results are compared with mean field calculations and semiclassical estimates based on the Donau-Frauendorf formalism. The mercury bands show significantly lower B(M1)/B(E2) branching ratios as compared with similar bands in light lead nuclei. This difference may be more readily explained by a difference in single-particle structure rather than by large differences in deformation between the lead and mercury configurations.
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| 45. |
- Cederwall, Bo, et al.
(författare)
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PROPERTIES OF SUPERDEFORMED BANDS IN DY-153
- 1995
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Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 346:3-4, s. 244-250
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Tidskriftsartikel (refereegranskat)abstract
- Two new superdeformed (SD) bands in Dy-153, in addition to the three previously observed, have been studied with the GAMMASPHERE detector array. Assignments to single-neutron orbits in the SD potential are made based on the band properties. Evidence for a band interaction at very high spins, possibly involving the first N = 7 proton intruder orbital, is observed in the strongest populated SD band. Furthermore, evidence far a Delta I = 2 staggering is also found in this SD band.
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| 46. |
- de Kleer, I. M., et al.
(författare)
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Autologous stem cell transplantation for refractory juvenile idiopathic arthritis: analysis of clinical effects, mortality, and transplant related morbidity
- 2004
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Ingår i: Ann Rheum Dis. - : BMJ. - 0003-4967. ; 63:10, s. 1318-26
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate the safety and efficacy of autologous stem cell transplantation (ASCT) for refractory juvenile idiopathic arthritis (JIA). DESIGN: Retrospective analysis of follow up data on 34 children with JIA who were treated with ASCT in nine different European transplant centres. Rheumatological evaluation employed a modified set of core criteria. Immunological reconstitution and infectious complications were monitored at three month intervals after transplantation. RESULTS: Clinical follow up ranged from 12 to 60 months. Eighteen of the 34 patients (53%) with a follow up of 12 to 60 months achieved complete drug-free remission. Seven of these patients had previously failed treatment with anti-TNF. Six of the 34 patients (18%) showed a partial response (ranging from 30% to 70% improvement) and seven (21%) were resistant to ASCT. Infectious complications were common. There were three cases of transplant related mortality (9%) and two of disease related mortality (6%). CONCLUSIONS: ASCT in severely ill patients with JIA induces a drug-free remission of the disease and a profound increase in general wellbeing in a substantial proportion of patients, but the procedure carries a significant mortality risk. The following adjustments are proposed for future protocols: (1) elimination of total body irradiation from the conditioning regimen; (2) prophylactic administration of antiviral drugs and intravenous immunoglobulins until there is a normal CD4+ T cell count.
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| 47. |
- Dianatinasab, Mostafa, et al.
(författare)
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Adherence to a Western dietary pattern and risk of bladder cancer : A pooled analysis of 13 cohort studies of the Bladder Cancer Epidemiology and Nutritional Determinants international study
- 2020
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 147:12, s. 3394-3403
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Tidskriftsartikel (refereegranskat)abstract
- Little is known about the association of diet with risk of bladder cancer. This might be due to the fact that the majority of studies have focused on single food items, rather than dietary patterns, which may better capture any influence of diet on bladder cancer risk. We aimed to investigate the association between a measure of Western dietary pattern and bladder cancer risk. Associations between adherence to a Western dietary pattern and risk of developing bladder cancer were assessed by pooling data from 13 prospective cohort studies in the “BLadder cancer Epidemiology and Nutritional Determinants” (BLEND) study and applying Cox regression analysis. Dietary data from 580 768 study participants, including 3401 incident cases, and 577 367 noncases were analyzed. A direct and significant association was observed between higher adherence to a Western dietary pattern and risk of bladder cancer (hazard ratio (HR) comparing highest with lowest tertile scores: 1.54, 95% confidence interval (CI): 1.37, 1.72; P-trend =.001). This association was observed for men (HR comparing highest with lowest tertile scores: 1.72; 95% CI: 1.51, 1.96; P-trend =.001), but not women (P-het =.001). Results were consistent with HR above 1.00 after stratification on cancer subtypes (nonmuscle-invasive and muscle-invasive bladder cancer). We found evidence that adherence to a Western dietary pattern is associated with an increased risk of bladder cancer for men but not women.
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| 48. |
- Dianatinasab, Mostafa, et al.
(författare)
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The association between meat and fish consumption and bladder cancer risk : a pooled analysis of 11 cohort studies
- 2021
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Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 36:8, s. 781-792
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Tidskriftsartikel (refereegranskat)abstract
- Evidence on the effects of meat consumption from different sources on the risk of bladder cancer (BC) is limited and controversial. Therefore, this study aimed to evaluate the associations between meat consumption and BC risk using a pooled data approach. Individual data from 11 prospective cohorts comprising 2848 BC cases and 515,697 non-cases with a total of 5,498,025 person-years of follow-up was pooled and analysed to investigate the potential associations between total red meat and products, red meat, processed meat, poultry and total fish and BC risk. Hazard ratios (HRs), with corresponding 95% confidence intervals (CIs), were estimated using Cox regression models stratified on cohort. Overall, an increased BC risk was found for high intake of organ meat (HR comparing highest with lowest tertile: 1.18, 95% CI: 1.03, 1.36, p-trend = 0.03). On the contrary, a marginally inverse association was observed for total fish intake and BC risk among men (HR comparing highest with lowest tertile: 0.79, 95% CI 0.65, 0.97, p-trend = 0.04). No associations were observed for other meat sources. Results of this prospective study suggest that organ meat consumption may be associated with BC development. Replication in large-scale prospective studies and investigation of possible causal mechanisms is needed.
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| 49. |
- Djoussé, L, et al.
(författare)
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Interaction of normal and expanded CAG repeat sizes influences age at onset of Huntington disease.
- 2003
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Ingår i: American Journal of Medical Genetics. Part A. - : Wiley. - 1552-4825 .- 1552-4833. ; 119A:3, s. 279-82
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Tidskriftsartikel (refereegranskat)abstract
- Huntington disease (HD) is a neurodegenerative disorder caused by the abnormal expansion of CAG repeats in the HD gene on chromosome 4p16.3. Past studies have shown that the size of expanded CAG repeat is inversely associated with age at onset (AO) of HD. It is not known whether the normal Huntington allele size influences the relation between the expanded repeat and AO of HD. Data collected from two independent cohorts were used to test the hypothesis that the unexpanded CAG repeat interacts with the expanded CAG repeat to influence AO of HD. In the New England Huntington Disease Center Without Walls (NEHD) cohort of 221 HD affected persons and in the HD-MAPS cohort of 533 HD affected persons, we found evidence supporting an interaction between the expanded and unexpanded CAG repeat sizes which influences AO of HD (P = 0.08 and 0.07, respectively). The association was statistically significant when both cohorts were combined (P = 0.012). The estimated heritability of the AO residual was 0.56 after adjustment for normal and expanded repeats and their interaction. An analysis of tertiles of repeats sizes revealed that the effect of the normal allele is seen among persons with large HD repeat sizes (47-83). These findings suggest that an increase in the size of the normal repeat may mitigate the expression of the disease among HD affected persons with large expanded CAG repeats.
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| 50. |
- Ettema, Thijs J G, et al.
(författare)
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Molecular characterization of a conserved archaeal copper resistance (cop) gene cluster and its copper-responsive regulator in Sulfolobus solfataricus P2.
- 2006
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Ingår i: Microbiology. - : Microbiology Society. - 1350-0872 .- 1465-2080. ; 152:Pt 7, s. 1969-79
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Tidskriftsartikel (refereegranskat)abstract
- Using a comparative genomics approach, a copper resistance gene cluster has been identified in multiple archaeal genomes. The cop cluster is predicted to encode a metallochaperone (CopM), a P-type copper-exporting ATPase (CopA) and a novel, archaea-specific transcriptional regulator (CopT) which might control the expression of the cop genes. Sequence analysis revealed that CopT has an N-terminal DNA-binding helix-turn-helix domain and a C-terminal TRASH domain; TRASH is a novel domain which has recently been proposed to be uniquely involved in metal-binding in sensors, transporters and trafficking proteins in prokaryotes. The present study describes the molecular characterization of the cop gene cluster in the thermoacidophilic crenarchaeon Sulfolobus solfataricus. The polycistronic copMA transcript was found to accumulate in response to growth-inhibiting copper concentrations, whereas copT transcript abundance appeared to be constitutive. DNA-binding assays revealed that CopT binds to the copMA promoter at multiple sites, both upstream and downstream of the predicted TATA-BRE site. Copper was found to specifically modulate the affinity of DNA binding by CopT. This study describes a copper-responsive operon in archaea, a new family of archaeal DNA-binding proteins, and supports the idea that this domain plays a prominent role in the archaeal copper response. A model is proposed for copper-responsive transcriptional regulation of the copMA gene cluster.
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