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- Lion, T., et al.
(författare)
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The EuroChimerism concept for a standardized approach to chimerism analysis after allogeneic stem cell transplantation
- 2012
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 26:8, s. 1821-1828
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Tidskriftsartikel (refereegranskat)abstract
- Hematopoietic stem cell transplantation is becoming an increasingly important approach to treatment of different malignant and non-malignant disorders. There is thus growing demand for diagnostic assays permitting the surveillance of donor/recipient chimerism posttransplant. Current techniques are heterogeneous, rendering uniform evaluation and comparison of diagnostic results between centers difficult. Leading laboratories from 10 European countries have therefore performed a collaborative study supported by a European grant, the EuroChimerism Concerted Action, with the aim to develop a standardized diagnostic methodology for the detection and monitoring of chimerism in patients undergoing allogeneic stem cell transplantation. Following extensive analysis of a large set of microsatellite/short tandem repeat (STR) loci, the EuroChimerism (EUC) panel comprising 13 STR markers was established with the aim to optimally meet the specific requirements of quantitative chimerism analysis. Based on highly stringent selection criteria, the EUC panel provides multiple informative markers in any transplant setting. The standardized STR-PCR tests permit detection of donor-or recipient-derived cells at a sensitivity ranging between 0.8 and 1.6%. Moreover, the EUC assay facilitates accurate and reproducible quantification of donor and recipient hematopoietic cells. Wide use of the European-harmonized protocol for chimerism analysis presented will provide a basis for optimal diagnostic support and timely treatment decisions.
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- Drakvik, E., et al.
(författare)
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Statement on advancing the assessment of chemical mixtures and their risks for human health and the environment
- 2020
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 134
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Tidskriftsartikel (refereegranskat)abstract
- The number of anthropogenic chemicals, manufactured, by-products, metabolites and abiotically formed transformation products, counts to hundreds of thousands, at present. Thus, humans and wildlife are exposed to complex mixtures, never one chemical at a time and rarely with only one dominating effect. Hence there is an urgent need to develop strategies on how exposure to multiple hazardous chemicals and the combination of their effects can be assessed. A workshop, “Advancing the Assessment of Chemical Mixtures and their Risks for Human Health and the Environment” was organized in May 2018 together with Joint Research Center in Ispra, EU-funded research projects and Commission Services and relevant EU agencies. This forum for researchers and policy-makers was created to discuss and identify gaps in risk assessment and governance of chemical mixtures as well as to discuss state of the art science and future research needs. Based on the presentations and discussions at this workshop we want to bring forward the following Key Messages: • We are at a turning point: multiple exposures and their combined effects require better management to protect public health and the environment from hazardous chemical mixtures. • Regulatory initiatives should be launched to investigate the opportunities for all relevant regulatory frameworks to include prospective mixture risk assessment and consider combined exposures to (real-life) chemical mixtures to humans and wildlife, across sectors. • Precautionary approaches and intermediate measures (e.g. Mixture Assessment Factor) can already be applied, although, definitive mixture risk assessments cannot be routinely conducted due to significant knowledge and data gaps. • A European strategy needs to be set, through stakeholder engagement, for the governance of combined exposure to multiple chemicals and mixtures. The strategy would include research aimed at scientific advancement in mechanistic understanding and modelling techniques, as well as research to address regulatory and policy needs. Without such a clear strategy, specific objectives and common priorities, research, and policies to address mixtures will likely remain scattered and insufficient. © 2019 The Authors
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- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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- Helfricht, A, et al.
(författare)
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Loss of ZBTB24 impairs nonhomologous end-joining and class-switch recombination in patients with ICF syndrome
- 2020
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Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 217:11
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Tidskriftsartikel (refereegranskat)abstract
- The autosomal recessive immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome is a genetically heterogeneous disorder. Despite the identification of the underlying gene defects, it is unclear how mutations in any of the four known ICF genes cause a primary immunodeficiency. Here we demonstrate that loss of ZBTB24 in B cells from mice and ICF2 patients affects nonhomologous end-joining (NHEJ) during immunoglobulin class-switch recombination and consequently impairs immunoglobulin production and isotype balance. Mechanistically, we found that ZBTB24 associates with poly(ADP-ribose) polymerase 1 (PARP1) and stimulates its auto-poly(ADP-ribosyl)ation. The zinc-finger in ZBTB24 binds PARP1-associated poly(ADP-ribose) chains and mediates the PARP1-dependent recruitment of ZBTB24 to DNA breaks. Moreover, through its association with poly(ADP-ribose) chains, ZBTB24 protects them from degradation by poly(ADP-ribose) glycohydrolase (PARG). This facilitates the poly(ADP-ribose)-dependent assembly of the LIG4/XRCC4 complex at DNA breaks, thereby promoting error-free NHEJ. Thus, we uncover ZBTB24 as a regulator of PARP1-dependent NHEJ and class-switch recombination, providing a molecular basis for the immunodeficiency in ICF2 syndrome.
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- Klimkowska, Agata, et al.
(författare)
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Are we restoring functional fens? : The outcomes of restoration projects in fens re-analysed with plant functional traits
- 2019
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Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 14:4
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Tidskriftsartikel (refereegranskat)abstract
- In peatland restoration we often lack an information whether re-established ecosystems are functionally similar to non-degraded ones. We re-analysed the long-term outcomes of restoration on vegetation and plant functional traits in 38 European fens restored by rewetting (18 sites) and topsoil removal (20 sites). We used traits related to nutrient acquisition strategies, competitiveness, seed traits, and used single- and multi-trait metrics. A separate set of vegetation records from near-natural fens with diverse plant communities was used to generate reference values to aid the comparisons. We found that both restoration methods enhanced the similarity of species composition to non-degraded systems but trait analysis revealed differences between the two approaches. Traits linked to nutrient acquisition strategies indicated that topsoil removal was more effective than rewetting. After topsoil removal competitive species in plant communities had decreased, while stress-tolerant species had increased. A substantial reduction in nutrient availability ruled out the effect of initial disturbance. An ability to survive and grow in anoxic conditions was enhanced after restoration, but the reference values were not achieved. Rewetting was more effective than topsoil removal in restricting variation in traits values permitted in re-developing vegetation. We found no indication of a shift towards reference in seed traits, which suggested that dispersal constraint and colonization deficit can be a widespread phenomena. Two functional diversity indices: functional richness and functional dispersion showed response to restoration and shifted values towards reference mires and away from the degraded systems. We concluded that targeting only one type of environmental stressor does not lead to a recovery of fens, as it provides insufficient level of stress to restore a functional ecosystem. In general, restoration efforts do not ensure the re-establishment and long-term persistence of fens. Restoration efforts result in recovery of fen ecosystems, confirmed with our functional trait analysis, although more rigid actions are needed for restoring fully functional mires, by achieving high and constant levels of anoxia and nutrient stresses.
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