| 1. |
- Betancur, Catalina, et al.
(författare)
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Serotonin transporter gene polymorphisms and hyperserotonemia in autistic disorder
- 2002
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 7:1, s. 67-71
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have provided conflicting evidence regarding the association of the serotonin transporter (5-HTT) gene with autism. Two polymorphisms have been identified in the human 5-HTT gene, a VNTR in intron 21 and a functional deletion/insertion in the promoter region (5-HTTLPR) with short and long variants.2 Positive associations of the 5-HTTLPR polymorphism with autism have been reported by two family-based studies, but one found preferential transmission of the short allele3 and the other of the long allele.4 Two subsequent studies failed to find evidence of transmission disequilibrium at the 5-HTTLPR locus.5,6 These conflicting results could be due to heterogeneity of clinical samples with regard to serotonin (5-HT) blood levels, which have been found to be elevated in some autistic subjects.7–9 Thus, we examined the association of the 5-HTTLPR and VNTR polymorphisms of the 5-HTT gene with autism, and we investigated the relationship between 5-HTT variants and whole-blood 5-HT. The transmission/disequilibrium test (TDT) revealed no linkage disequilibrium at either loci in a sample of 96 families comprising 43 trios and 53 sib pairs. Furthermore, no significant relationship between 5-HT blood levels and 5-HTT gene polymorphisms was found. Our results suggest that the 5-HTT gene is unlikely to play a major role as a susceptibility factor in autism.
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| 2. |
- Charpin, Laurent, et al.
(författare)
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Ageing and air leakage assessment of a nuclear reactor containment mock-up : VERCORS 2nd benchmark
- 2021
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Ingår i: Nuclear Engineering and Design. - : Elsevier BV. - 0029-5493. ; 377
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Tidskriftsartikel (refereegranskat)abstract
- Electricité de France (EDF) operates a large fleet of nuclear reactors and is responsible for demonstrating the safety of facilities, including concrete containment buildings (CCB), which are non-replaceable components. The leak-tightness of CCBs is assessed every 10 years during integrated leak-rate tests (IRLT). For double-wall containments, which have no metallic liners, the leak-tightness is strongly influenced by the degree of cracking of concrete and opening of the cracks, which mostly depends on (a) the prestress decrease due to the delayed strains of concrete and to a lesser extent due to relaxation of tendons steel, and (b) the saturation degree of the Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation concrete wall. Therefore, to optimize the maintenance programs on CCBs, it is important to predict the evolution of drying, creep and shrinkage strains of concrete to be able to correctly assess the pre-stress losses, and finally the air leak-tightness at a structural level during pressure tests or under accidental loadings. To improve our understanding and identify the best modelling practices on this issue, a large experimental program called VERCORS was launched in 2014. VERCORS is a 1/3 mock-up of a 1300 MWe nuclear reactor CCB. It has been widely instrumented, and its concrete thoroughly characterized. A specific attention has been paid to ensure it is consistent with real CBBs features in EDF's nuclear fleet. To complement its internal R&D efforts, EDF decided to associate external partners to this program. One of the means for this is the organization of benchmarks, where all teams are given data and information about the mock-up and are asked to quantitatively predict its behaviour. The present paper reports the organization and findings of the 2nd benchmark which was organized in 2018 and gathered several international teams around the same objective: improve the confidence in the modelling of structural behaviour as well as the leak-tightness of concrete in containment walls under pressure test loading. The benchmark has shown once again that predicting the mechanical and leakage behaviour of containment buildings is a difficult task. The benchmark also yielded interesting information about the possibility to use spatially reduced models to predict the mechanical behaviour and leakage and underlined the fact that more research must be done to better predict the localization of cracks and leakage. Some lessons have been learnt for the next benchmark: EDF will ask to clarify further the calibration methods, will give more data (including drying, creep and shrinkage at different temperatures and moisture measurements in the mock-up), and will help the participants using local leakage data by projecting the raw measurements on a regular grid, so that the local leakage models can be improved.
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| 3. |
- Droguerre, Marine, et al.
(författare)
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A New Tool for In Vivo Study of Astrocyte Connexin 43 in Brain.
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Astrocytes are glial cells organized in dynamic and structured networks in the brain. These plastic networks, involving key proteins such as connexin 43 (Cx43), are engaged in fine neuronal tuning and have recently been considered as emerging therapeutic targets in central nervous system disorders. We developed and validated a new application of the manganese-enhanced magnetic resonance imaging (MEMRI) technique allowing in vivo investigations of astrocyte-neuron interactions through quantification of brain Cx43 functional activity. The proof of concept has been achieved by quantification of MEMRI signals in brain after either local astrocyte-specific Cx43 knockdown with shRNA or systemic administration of Cx43 blockers. Unilateral hippocampal Cx43 genetical silencing was associated with an ipsilateral local increase of MEMRI signal. Furthermore, Cx43 blockers also enhanced MEMRI signal responses in hippocampus. Altogether, these data reveal the MEMRI technique as a tool for quantitative imaging of in vivo Cx43-dependent function in astrocytes under physiological and pathological conditions.
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| 4. |
- Droguerre, Marine, et al.
(författare)
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Efficacy of THN201, a Combination of Donepezil and Mefloquine, to Reverse Neurocognitive Deficits in Alzheimer's Disease.
- 2020
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Ingår i: Frontiers in Neuroscience. - : Frontiers Media SA. - 1662-4548 .- 1662-453X. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Donepezil (DPZ) is an acetylcholinesterase inhibitor used in Alzheimer's disease to restore cognitive functions but is endowed with limited efficacy. Recent studies pointed out the implication of astroglial networks in cognitive processes, notably via astrocyte connexins (Cxs), proteins involved in gap junction intercellular communications. Hence, we investigated the impact on cognition of pharmacological or genetic modulations of those astrocyte Cxs during DPZ challenge in two rodent models of Alzheimer's disease-like memory deficits. We demonstrated that the Cx modulator mefloquine (MEF) significantly enhanced the procognitive effect of DPZ in both models. In parallel, we determined that MEF potentiated DPZ-induced release of acetylcholine in hippocampus. Finally, local genetic silencing of astrocyte Cxs in the hippocampus was also found to enhance the procognitive effect of DPZ, pointing out the importance of Cx-dependent astrocyte networks in memory processes.
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| 5. |
- Nielsen, Rasmus J., et al.
(författare)
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Integrated ecological–economic fisheries models—Evaluation, review and challenges for implementation
- 2018
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Ingår i: Fish and Fisheries. - : Wiley. - 1467-2960 .- 1467-2979. ; 19:1, s. 1-29
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Forskningsöversikt (refereegranskat)abstract
- Marine ecosystems evolve under many interconnected and area-specific pressures. To fulfil society's intensifying and diversifying needs while ensuring ecologically sustainable development, more effective marine spatial planning and broader-scope management of marine resources is necessary. Integrated ecological–economic fisheries models (IEEFMs) of marine systems are needed to evaluate impacts and sustainability of potential management actions and understand, and anticipate ecological, economic and social dynamics at a range of scales from local to national and regional. To make these models most effective, it is important to determine how model characteristics and methods of communicating results influence the model implementation, the nature of the advice that can be provided and the impact on decisions taken by managers. This article presents a global review and comparative evaluation of 35 IEEFMs applied to marine fisheries and marine ecosystem resources to identify the characteristics that determine their usefulness, effectiveness and implementation. The focus is on fully integrated models that allow for feedbacks between ecological and human processes although not all the models reviewed achieve that. Modellers must invest more time to make models user friendly and to participate in management fora where models and model results can be explained and discussed. Such involvement is beneficial to all parties, leading to improvement of models and more effective implementation of advice, but demands substantial resources which must be built into the governance process. It takes time to develop effective processes for using IEEFMs requiring a long-term commitment to integrating multidisciplinary modelling advice into management decision-making.
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| 6. |
- Roncal, Julissa, et al.
(författare)
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Active transposable elements recover species boundaries and geographic structure in Madagascan coffee species
- 2016
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Ingår i: Molecular Genetics and Genomics. - : Springer Science and Business Media LLC. - 1617-4615 .- 1617-4623. ; 291:1, s. 155-168
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Tidskriftsartikel (refereegranskat)abstract
- The completion of the genome assembly for the economically important coffee plant Coffea canephora (Rubiaceae) has allowed the use of bioinformatic tools to identify and characterize a diverse array of transposable elements (TEs), which can be used in evolutionary studies of the genus. An overview of the copy number and location within the C. canephora genome of four TEs is presented. These are tested for their use as molecular markers to unravel the evolutionary history of the Millotii Complex, a group of six wild coffee (Coffea) species native to Madagascar. Two TEs from the Gypsy superfamily successfully recovered some species boundaries and geographic structure among samples, whereas a TE from the Copia superfamily did not. Notably, species occurring in evergreen moist forests of eastern and southeastern Madagascar were divergent with respect to species in other habitats and regions. Our results suggest that the peak of transpositional activity of the Gypsy and Copia TEs occurred, respectively, before and after the speciation events of the tested Madagascan species. We conclude that the utilization of active TEs has considerable potential to unravel the evolutionary history and delimitation of closely related Coffea species. However, the selection of TE needs to be experimentally tested, since each element has its own evolutionary history. Different TEs with similar copy number in a given species can render different dendrograms; thus copy number is not a good selection criterion to attain phylogenetic resolution.
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