| 1. |
- Fugier, Charlotte, et al.
(författare)
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Misregulated alternative splicing of BIN1 is associated with T tubule alterations and muscle weakness in myotonic dystrophy
- 2011
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Ingår i: Nature medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 17:6, s. 720-725
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Tidskriftsartikel (refereegranskat)abstract
- Myotonic dystrophy is the most common muscular dystrophy in adults and the first recognized example of an RNA-mediated disease. Congenital myotonic dystrophy (CDM1) and myotonic dystrophy of type 1 (DM1) or of type 2 (DM2) are caused by the expression of mutant RNAs containing expanded CUG or CCUG repeats, respectively. These mutant RNAs sequester the splicing regulator Muscleblind-like-1 (MBNL1), resulting in specific misregulation of the alternative splicing of other pre-mRNAs. We found that alternative splicing of the bridging integrator-1 (BIN1) pre-mRNA is altered in skeletal muscle samples of people with CDM1, DM1 and DM2. BIN1 is involved in tubular invaginations of membranes and is required for the biogenesis of muscle T tubules, which are specialized skeletal muscle membrane structures essential for excitation-contraction coupling. Mutations in the BIN1 gene cause centronuclear myopathy, which shares some histopathological features with myotonic dystrophy. We found that MBNL1 binds the BIN1 pre-mRNA and regulates its alternative splicing. BIN1 missplicing results in expression of an inactive form of BIN1 lacking phosphatidylinositol 5-phosphate-binding and membrane-tubulating activities. Consistent with a defect of BIN1, muscle T tubules are altered in people with myotonic dystrophy, and membrane structures are restored upon expression of the normal splicing form of BIN1 in muscle cells of such individuals. Finally, reproducing BIN1 splicing alteration in mice is sufficient to promote T tubule alterations and muscle weakness, a predominant feature of myotonic dystrophy.
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| 2. |
- Ampoorter, Evy, et al.
(författare)
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Tree diversity is key for promoting the diversity and abundance of forest-associated taxa in Europe
- 2020
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Ingår i: Oikos. - : Wiley. - 0030-1299 .- 1600-0706. ; 129:2, s. 133-146
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Tidskriftsartikel (refereegranskat)abstract
- Plant diversity is an important driver of diversity at other trophic levels, suggesting that cascading extinctions could reduce overall biodiversity. Most evidence for positive effects of plant diversity comes from grasslands. Despite the fact that forests are hotspots of biodiversity, the importance of tree diversity, in particular its relative importance compared to other management related factors, in affecting forest-associated taxa is not well known. To address this, we used data from 183 plots, located in different forest types, from Mediterranean to Boreal, and established along a climatic gradient across six European countries (FunDivEUROPE project). We tested the influence of tree diversity, tree functional composition (i.e. functional trait values), forest structure, climate and soil on the diversity and abundance/activity of nine taxa (bats, birds, spiders, microorganisms, earthworms, ungulates, foliar fungal pathogens, defoliating insects and understorey plants) and on their overall diversity and abundance/activity (multidiversity, multiabundance/activity). Tree diversity was a key driver of taxon-level and overall forest-associated biodiversity, along with tree functional composition, forest structure, climate and soil. Both tree species richness and functional diversity (variation in functional trait values) were important. The effects of tree diversity on the abundance/activity of forest-associated taxa were less consistent. Nonetheless, spiders, ungulates and foliar fungal pathogens were all more abundant/active in diverse forests. Tree functional composition and structure were also important drivers of abundance/activity: conifer stands had lower overall multidiversity (although the effect was driven by defoliating insects), while stands with potentially tall trees had lower overall multiabundance/activity. We found more synergies than tradeoffs between diversity and abundance/activity of different taxa, suggesting that forest management can promote high diversity across taxa. Our results clearly show the high value of mixed forest stands for multiple forest-associated taxa and indicate that multiple dimensions of tree diversity (taxonomic and functional) are important.
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| 3. |
- Baeten, Lander, et al.
(författare)
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Identifying the tree species compositions that maximize ecosystem functioning in European forests
- 2019
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Ingår i: Journal of Applied Ecology. - : Wiley. - 0021-8901 .- 1365-2664. ; 56:3, s. 733-744
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Tidskriftsartikel (refereegranskat)abstract
- 1. Forest ecosystem functioning generally benefits from higher tree species richness, but variation within richness levels is typically large. This is mostly due to the contrasting performances of communities with different compositions. Evidence-based understanding of composition effects on forest productivity, as well as on multiple other functions will enable forest managers to focus on the selection of species that maximize functioning, rather than on diversity per se.2. We used a dataset of 30 ecosystem functions measured in stands with different species richness and composition in six European forest types. First, we quantified whether the compositions that maximize annual above-ground wood production (productivity) generally also fulfil the multiple other ecosystem functions (multifunctionality). Then, we quantified the species identity effects and strength of interspecific interactions to identify the "best" and "worst" species composition for multifunctionality. Finally, we evaluated the real-world frequency of occurrence of best and worst mixtures, using harmonized data from multiple national forest inventories.3. The most productive tree species combinations also tended to express relatively high multifunctionality, although we found a relatively wide range of compositions with high- or low-average multifunctionality for the same level of productivity. Monocultures were distributed among the highest as well as the lowest performing compositions. The variation in functioning between compositions was generally driven by differences in the performance of the component species and, to a lesser extent, by particular interspecific interactions. Finally, we found that the most frequent species compositions in inventory data were monospecific stands and that the most common compositions showed below-average multifunctionality and productivity.4. Synthesis and applications. Species identity and composition effects are essential to the development of high-performing production systems, for instance in forestry and agriculture. They therefore deserve great attention in the analysis and design of functional biodiversity studies if the aim is to inform ecosystem management. A management focus on tree productivity does not necessarily trade-off against other ecosystem functions; high productivity and multifunctionality can be combined with an informed selection of tree species and species combinations.
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| 4. |
- Bonnetain, Franck, et al.
(författare)
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Guidelines for time-to-event end-point definitions in trials for pancreatic cancer : Results of the DATECAN initiative (Definition for the Assessment of Time-to-event End-points in CANcer trials)
- 2014
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 50:17, s. 2983-2993
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Forskningsöversikt (refereegranskat)abstract
- Background: Using potential surrogate end-points for overall survival (OS) such as Disease-Free- (DFS) or Progression-Free Survival (PFS) is increasingly common in randomised controlled trials (RCTs). However, end-points are too often imprecisely defined which largely contributes to a lack of homogeneity across trials, hampering comparison between them. The aim of the DATECAN (Definition for the Assessment of Time-to-event End-points in CANcer trials)-Pancreas project is to provide guidelines for standardised definition of time-to-event end-points in RCTs for pancreatic cancer. Methods: Time-to-event end-points currently used were identified from a literature review of pancreatic RCT trials (2006-2009). Academic research groups were contacted for participation in order to select clinicians and methodologists to participate in the pilot and scoring groups (>30 experts). A consensus was built after 2 rounds of the modified Delphi formal consensus approach with the Rand scoring methodology (range: 1-9). Results: For pancreatic cancer, 14 time to event end-points and 25 distinct event types applied to two settings (detectable disease and/or no detectable disease) were considered relevant and included in the questionnaire sent to 52 selected experts. Thirty experts answered both scoring rounds. A total of 204 events distributed over the 14 end-points were scored. After the first round, consensus was reached for 25 items; after the second consensus was reached for 156 items; and after the face-to-face meeting for 203 items. Conclusion: The formal consensus approach reached the elaboration of guidelines for standardised definitions of time-to-event end-points allowing cross-comparison of RCTs in pancreatic cancer.
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| 5. |
- Boucly, Anthony, et al.
(författare)
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Soft X-ray Heterogeneous Radiolysis of Pyridine in the Presence of Hydrated Strontium-Hydroxyhectorite and its Monitoring by Near-Ambient Pressure Photoelectron Spectroscopy
- 2018
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- The heterogeneous radiolysis of organic molecules in clays is a matter of considerable interest in astrochemistry and environmental sciences. However, little is known about the effects of highly ionizing soft X-rays. By combining monochromatized synchrotron source irradiation with in situ Near Ambient Pressure X-ray Photoelectron Spectroscopy (in the mbar range), and using the synoptic view encompassing both the gas and condensed phases, we found the water and pyridine pressure conditions under which pyridine is decomposed in the presence of synthetic Sr2+-hydroxyhectorite. The formation of a pyridine/water/Sr2+ complex, detected from the Sr 3d and N 1s core-level binding energies, likely presents a favorable situation for the radiolytic breaking of the O-H bond of water molecules adsorbed in the clay and the subsequent decomposition of the molecule. However, decomposition stops when the pyridine pressure exceeds a critical value. This observation can be related to a change in the nature of the active radical species with the pyridine loading. This highlights the fact that the destruction of the molecule is not entirely determined by the properties of the host material, but also by the inserted organic species. The physical and chemical causes of the present observations are discussed.
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| 6. |
- Câmara-Costa, Hugo, et al.
(författare)
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Neuropsychological Outcome of Children Treated for Standard Risk Medulloblastoma in the PNET4 European Randomized Controlled Trial of Hyperfractionated Versus Standard Radiation Therapy and Maintenance Chemotherapy.
- 2015
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Ingår i: International journal of radiation oncology, biology, physics. - : Elsevier BV. - 1879-355X .- 0360-3016. ; 92:5, s. 978-85
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Tidskriftsartikel (refereegranskat)abstract
- In the European HIT-SIOP PNET4 randomized controlled trial, children with standard risk medulloblastoma were allocated to hyperfractionated radiation therapy (HFRT arm, including a partially focused boost) or standard radiation therapy (STRT arm), followed, in both arms, by maintenance chemotherapy. Event-free survival was similar in both arms. Previous work showed that the HFRT arm was associated with worse growth and better questionnaire-based executive function, especially in children <8years of age at diagnosis. Therefore, the aim of this study was to compare performance-based cognitive outcomes between treatment arms.
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| 7. |
- De Vleeschouwer, Francois, et al.
(författare)
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Quantitative WD-XRF calibration for small ceramic samples and their source material
- 2011
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Ingår i: Geoarchaeology. - : Wiley. - 0883-6353 .- 1520-6548. ; 26:3, s. 440-450
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Tidskriftsartikel (refereegranskat)abstract
- A wavelength-dispersive X-ray fluorescence (WD-XRF) calibration is developed for small powdered samples (300 mg) with the purpose of analyzing ceramic artifacts that might be available only in limited quantity. This is compared to a conventional calibration using a larger sample mass (2 g). The comparison of elemental intensities obtained in both calibrations shows that the decrease in analyzed sample mass results in a linear decrease in measured intensity for the analyzed elements. This indicates that the small-and large-sample calibrations are comparable. Moreover, the elemental contents of four ceramic sherds and two potential clay sources fall well within the range of the certified reference materials that are the basis of the calibration curves. The advantage with the analytical method presented here is that it is rapid and requires only a small amount of sample that can easily be re-used for further analyses. This method has great potential in ceramic provenance studies. (C) 2011 Wiley Periodicals, Inc.
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| 8. |
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| 9. |
- Husler, Dario, et al.
(författare)
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Dictyostelium lacking the single atlastin homolog Sey1 shows aberrant ER architecture, proteolytic processes and expansion of the Legionella-containing vacuole
- 2021
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Ingår i: Cellular Microbiology. - : WILEY. - 1462-5814 .- 1462-5822. ; 23:5
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Tidskriftsartikel (refereegranskat)abstract
- Dictyostelium discoideum Sey1 is the single ortholog of mammalian atlastin 1-3 (ATL1-3), which are large homodimeric GTPases mediating homotypic fusion of endoplasmic reticulum (ER) tubules. In this study, we generated a D. discoideum mutant strain lacking the sey1 gene and found that amoebae deleted for sey1 are enlarged, but grow and develop similarly to the parental strain. The increment sey1 mutant amoebae showed an altered ER architecture, and the tubular ER network was partially disrupted without any major consequences for other organelles or the architecture of the secretory and endocytic pathways. Macropinocytic and phagocytic functions were preserved; however, the mutant amoebae exhibited cumulative defects in lysosomal enzymes exocytosis, intracellular proteolysis, and cell motility, resulting in impaired growth on bacterial lawns. Moreover, increment sey1 mutant cells showed a constitutive activation of the unfolded protein response pathway (UPR), but they still readily adapted to moderate levels of ER stress, while unable to cope with prolonged stress. In D. discoideum increment sey1 the formation of the ER-associated compartment harbouring the bacterial pathogen Legionella pneumophila was also impaired. In the mutant amoebae, the ER was less efficiently recruited to the "Legionella-containing vacuole" (LCV), the expansion of the pathogen vacuole was inhibited at early stages of infection and intracellular bacterial growth was reduced. In summary, our study establishes a role of D. discoideum Sey1 in ER architecture, proteolysis, cell motility and intracellular replication of L. pneumophila.
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| 10. |
- Lindholm, Jerry, 1991-
(författare)
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Molecular-level controls on water and organics intercalation in layered minerals
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Layered minerals are naturally abundant and often display a large surface area in relation to their weight. For swelling layered minerals, most of this area is contained between the layers in the interlayer space. Their large surface area makes them interesting in many different fields and applications, such as adsorbents, catalysts or as carriers for other particles that can be intercalated and exchanged. In order for the materials to be used effectively, it is hence necessary to have a fundamental understanding of how these processes occur, and ways to predict them.To address adsorption of water, an isotherm model was created to describe the hydration process on layered materials. The model decomposed the process of adsorptions into internal and external, adsorption and condensation, and could specifically handle hydration in the expanding interlayer nanopores. Adsorption and desorption isotherms of two different materials, Montmorillonite and Birnessite was successfully modelled, where the former was ion-exchanged with the counter-cations Li+, Na+, K+, Cs+, Mg2+, Ca2+, Sr2+, Cu2+, whereas the latter contained K+. This indicated that this isotherm model is applicable to also other layered materials. The adsorption process was also characterized experimentally with vibrational spectroscopy (FTIR) and multivariate statistical techniques (MCR), in order to generate spectral- and concentration profiles of the involved components.In order to also investigate adsorption of different organic molecules, the intercalation of alcohols and a cationic surfactant was investigated in separate studies. Clay-water-alcohol systems of eight alcohols were characterized experimentally by XRD as well as by molecular dynamics simulations, using different combinations of classical force fields for the clay (ClayFF, ClayFFMod, INTERFACE) and for the alcohols (CGenFF, GAFF, OPLS). It was found that the optimal force field combination varied with the fitting approach. A brute force sensitivity analysis indicated that the comparison with the experimental XRD data was more dependent on the relative interlayer loading than the positions of the atoms, an important result for future similar benchmarking studies.By intercalating and adsorbing a cationic surfactant (CTAB) to Montmorillonite at increasing concentrations, the effects of solvent polarity and the CTAB interlayer content on the Montmorillonite interlayer swelling was investigated. It was found that moderately polar solvents such as DMSO, in combination with CTAB in a planar bilayer configuration resulted in the greatest adsorption of the lipophilic solute alizarin.
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| 11. |
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