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- Frati, G., et al.
(författare)
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Human iPSC-based models highlight defective glial and neuronal differentiation from neural progenitor cells in metachromatic leukodystrophy
- 2018
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Ingår i: Cell Death & Disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- The pathological cascade leading from primary storage to neural cell dysfunction and death in metachromatic leukodystrophy (MLD) has been poorly elucidated in human-derived neural cell systems. In the present study, we have modeled the progression of pathological events during the differentiation of patient-specific iPSCs to neuroepithelial progenitor cells (iPSC-NPCs) and mature neurons, astrocytes, and oligodendrocytes at the morphological, molecular, and biochemical level. We showed significant sulfatide accumulation and altered sulfatide composition during the differentiation of MLD iPSC-NPCs into neuronal and glial cells. Changes in sulfatide levels and composition were accompanied by the expansion of the lysosomal compartment, oxidative stress, and apoptosis. The neuronal and glial differentiation capacity of MLD iPSC-NPCs was significantly impaired. We showed delayed appearance and/or reduced levels of oligodendroglial and astroglial markers as well as reduced number of neurons and disorganized neuronal network. Restoration of a functional Arylsulfatase A (ARSA) enzyme in MLD cells using lentiviral-mediated gene transfer normalized sulfatide levels and composition, globally rescuing the pathological phenotype. Our study points to MLD iPSC-derived neural progeny as a useful in vitro model to assess the impact of ARSA deficiency along NPC differentiation into neurons and glial cells. In addition, iPSC-derived neural cultures allowed testing the impact of ARSA reconstitution/overexpression on disease correction and, importantly, on the biology and functional features of human NPCs, with important therapeutic implications.
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- Conradie, W., et al.
(författare)
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New species of Mongrel Frogs (Pyxicephalidae: Nothophryne) for northern Mozambique inselbergs
- 2018
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Ingår i: African Journal of Herpetology. - : Informa UK Limited. - 2156-4574 .- 2153-3660. ; 67:1, s. 61-85
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Tidskriftsartikel (refereegranskat)abstract
- Nothophryne Poynton, 1963 is a monotypic genus of frog, with the nominal species N. broadleyi found only on Mount Mulanje, in southern Malawi. Recent surveys in northern Mozambique, however, have uncovered at least four new species associated with four inselbergs (Mount Inago, Mount Namuli, Mount Ribaue and Taratibu Hills). Previous phylogenetic analyses using mitochondrial genes suggest that each mountain isolate has an endemic species of Nothophryne. Herein we provide a rediagnosis of the genus and comparative diagnoses of four new species based on new material.ZooBank urn:lsid:zoobank.org:pub:19C53BF3-BA52-4CAE-933F-5BBEE0AF0457
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- Gasser, D., et al.
(författare)
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Behaviour of geochronometers and timing of metamorphic reactions during deformation at lower crustal conditions: phase equilibrium modelling and U–Pb dating of zircon, monazite, rutile and titanite from the Kalak Nappe Complex, northern Norway.
- 2015
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Ingår i: Journal of Metamorphic Geology. - : Wiley. - 0263-4929 .- 1525-1314. ; 33, s. 513-534
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Tidskriftsartikel (refereegranskat)abstract
- This study investigates the behaviour of the geochronometers zircon, monazite, rutile and titanite in polyphase lower crustal rocks of the Kalak Nappe Complex, northern Norway. A pressure–temperature–time–deformation path is constructed by combining microstructural observations with P–T conditions derived from phase equilibrium modelling and U–Pb dating. The following tectonometamorphic evolution is deduced: A subvertical S1 fabric formed at ~730–775 °C and ~6.3–9.8 kbar, above the wet solidus in the sillimanite and kyanite stability fields. The event is dated at 702 ± 5 Ma by high-U zircon in a leucosome. Monazite grains that grew in the S1 fabric show surprisingly little variation in chemical composition compared to a large spread in (concordant) U–Pb dates from c. 800 to 600 Ma. This age spread could either represent protracted growth of monazite during high-grade metamorphism, or represent partially reset ages due to high-T diffusion. Both cases imply that elevated temperatures of >600 °C persisted for over c. 200 Ma, indicating relatively static conditions at lower crustal levels for most of the Neoproterozoic. The S1 fabric was overprinted by a subhorizontal S2 fabric, which formed at ~600–660 °C and ~10–12 kbar. Rutile that originally grew during the S1-forming event lost its Zr-in-rutile and U–Pb signatures during the S2-forming event. It records Zr-in-rutile temperatures of 550–660 °C and Caledonian ages of 440–420 Ma. Titanite grew at the expense of rutile at slightly lower temperatures of ~550 °C during ongoing S2 deformation; U–Pb ages of c. 440–430 Ma date its crystallization, giving a minimum estimate for the age of Caledonian metamorphism and the duration of Caledonian shearing. This study shows that (i) monazite can have a large spread in U–Pb dates despite a homogeneous composition; (ii) rutile may lose its Zr-in-rutile and U–Pb signature during an amphibolite facies overprint; and (iii) titanite may record crystallization ages during retrograde shearing. Therefore, in order to correctly interpret U–Pb ages from different geochronometers in a polyphase deformation and reaction history, they are ideally combined with microstructural observations and phase equilibrium modelling to derive a complete P–T–t–d path.
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