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- Chelban, V., et al.
(författare)
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PDXK mutations cause polyneuropathy responsive to pyridoxal 5′-phosphate supplementation
- 2019
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Ingår i: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 86:2, s. 225-240
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To identify disease-causing variants in autosomal recessive axonal polyneuropathy with optic atrophy and provide targeted replacement therapy. Methods: We performed genome-wide sequencing, homozygosity mapping, and segregation analysis for novel disease-causing gene discovery. We used circular dichroism to show secondary structure changes and isothermal titration calorimetry to investigate the impact of variants on adenosine triphosphate (ATP) binding. Pathogenicity was further supported by enzymatic assays and mass spectroscopy on recombinant protein, patient-derived fibroblasts, plasma, and erythrocytes. Response to supplementation was measured with clinical validated rating scales, electrophysiology, and biochemical quantification. Results: We identified biallelic mutations in PDXK in 5 individuals from 2 unrelated families with primary axonal polyneuropathy and optic atrophy. The natural history of this disorder suggests that untreated, affected individuals become wheelchair-bound and blind. We identified conformational rearrangement in the mutant enzyme around the ATP-binding pocket. Low PDXK ATP binding resulted in decreased erythrocyte PDXK activity and low pyridoxal 5′-phosphate (PLP) concentrations. We rescued the clinical and biochemical profile with PLP supplementation in 1 family, improvement in power, pain, and fatigue contributing to patients regaining their ability to walk independently during the first year of PLP normalization. Interpretation: We show that mutations in PDXK cause autosomal recessive axonal peripheral polyneuropathy leading to disease via reduced PDXK enzymatic activity and low PLP. We show that the biochemical profile can be rescued with PLP supplementation associated with clinical improvement. As B6 is a cofactor in diverse essential biological pathways, our findings may have direct implications for neuropathies of unknown etiology characterized by reduced PLP levels. ANN NEUROL 2019;86:225–240. © 2019 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.
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| 2. |
- Pastorello, A., et al.
(författare)
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A giant outburst two years before the core-collapse of a massive star
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 829-832
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Tidskriftsartikel (refereegranskat)abstract
- The death of massive stars produces a variety of supernovae, which are linked to the structure of the exploding stars(1,2). The detection of several precursor stars of type II supernovae has been reported ( see, for example, ref. 3), but we do not yet have direct information on the progenitors of the hydrogen-deficient type Ib and Ic supernovae. Here we report that the peculiar type Ib supernova SN 2006jc is spatially coincident with a bright optical transient(4) that occurred in 2004. Spectroscopic and photometric monitoring of the supernova leads us to suggest that the progenitor was a carbon-oxygen Wolf - Rayet star embedded within a helium-rich circumstellar medium. There are different possible explanations for this pre-explosion transient. It appears similar to the giant outbursts of luminous blue variable stars (LBVs) of 60 - 100 solar masses(5), but the progenitor of SN 2006jc was helium- and hydrogen-deficient ( unlike LBVs). An LBV-like outburst of a Wolf - Rayet star could be invoked, but this would be the first observational evidence of such a phenomenon. Alternatively, a massive binary system composed of an LBV that erupted in 2004, and a Wolf - Rayet star exploding as SN 2006jc, could explain the observations.
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| 7. |
- Hamacher, T, et al.
(författare)
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Characterization of the xylose-transporting properties of yeast hexose transporters and their influence on xylose utilization
- 2002
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Ingår i: Microbiology. - 1465-2080. ; 148, s. 2783-2788
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Tidskriftsartikel (refereegranskat)abstract
- For an economically feasible production of ethanol from plant biomass by microbial cells, the fermentation of xylose is important. As xylose uptake might be a limiting step for xylose fermentation by recombinant xylose-utilizing Saccharomyces cerevisiae cells a study of xylose uptake was performed. After deletion of all of the 18 hexose-transporter genes, the ability of the cells to take up and to grow on xylose was lost. Reintroduction of individual hexose-transporter genes in this strain revealed that at intermediate xylose concentrations the yeast high- and intermediate-affinity transporters Hxt4, Hxt5, Hxt7 and Ga12 are important xylose-transporting proteins. Several heterologous monosaccharide transporters from bacteria and plant cells did not confer sufficient uptake activity to restore growth on xylose. Overexpression of the xylose-transporting proteins in a xylose-utilizing PUA yeast strain did not result in faster growth on xylose under aerobic conditions nor did it enhance the xylose fermentation rate under anaerobic conditions. The results of this study suggest that xylose uptake does not determine the xylose flux under the conditions and in the yeast strains investigated.
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| 9. |
- Pastorello, A., et al.
(författare)
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SN 2009E : a faint clone of SN 1987A
- 2012
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 537
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Tidskriftsartikel (refereegranskat)abstract
- Context. 1987A-like events form a rare sub-group of hydrogen-rich core-collapse supernovae that are thought to originate from the explosion of blue supergiant stars. Although SN 1987A is the best known supernova, very few objects of this group have been discovered and, hence, studied. Aims. In this paper we investigate the properties of SN 2009E, which exploded in a relatively nearby spiral galaxy (NGC 4141) and that is probably the faintest 1987A-like supernova discovered so far. We also attempt to characterize this subgroup of core-collapse supernovae with the help of the literature and present new data for a few additional objects. Methods. The lack of early-time observations from professional telescopes is compensated by frequent follow-up observations performed by a number of amateur astronomers. This allows us to reconstruct a well-sampled light curve for SN 2009E. Spectroscopic observations which started about 2 months after the supernova explosion, highlight significant differences between SN 2009E and the prototypical SN 1987A. Modelling the data of SN 2009E allows us to constrain the explosion parameters and the properties of the progenitor star, and compare the inferred estimates with those available for the similar SNe 1987A and 1998A. Results. The light curve of SN 2009E is less luminous than that of SN 1987A and the other members of this class, and the maximum light curve peak is reached at a slightly later epoch than in SN 1987A. Late-time photometric observations suggest that SN 2009E ejected about 0.04 M-circle dot of Ni-56, which is the smallest Ni-56 mass in our sample of 1987A-like events. Modelling the observations with a radiation hydrodynamics code, we infer for SN 2009E a kinetic plus thermal energy of about 0.6 foe, an initial radius of similar to 7x10(12) cm and an ejected mass of similar to 19 M-circle dot. The photospheric spectra show a number of narrow (v approximate to 1800 km s(-1)) metal lines, with unusually strong Ba II lines. The nebular spectrum displays narrow emission lines of H, Na I, [Ca II] and [O I], with the [O I] feature being relatively strong compared to the [Ca II] doublet. The overall spectroscopic evolution is reminiscent of that of the faint Ni-56-poor type II-plateau supernovae. This suggests that SN 2009E belongs to the low-luminosity, low Ni-56 mass, low-energy tail in the distribution of the 1987A-like objects in the same manner as SN 1997D and similar events represent the faint tail in the distribution of physical properties for normal type II-plateau supernovae.
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| 10. |
- Tartaglia, L., et al.
(författare)
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Interacting supernovae and supernova impostors. SN 2007sv : the major eruption of a massive star in UGC 5979
- 2015
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 447:1, s. 117-131
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Tidskriftsartikel (refereegranskat)abstract
- We report the results of the photometric and spectroscopic monitoring campaign of the transient SN 2007sv. The observables are similar to those of Type IIn supernovae, a well-known class of objects whose ejecta interact with pre-existing circumstellar material (CSM). The spectra show a blue continuum at early phases and prominent Balmer lines in emission; however, the absolute magnitude at the discovery of SN 2007sv (M-R=-14.25 +/- 0.38) indicate it to be most likely a supernova impostor. This classification is also supported by the lack of evidence in the spectra of very high velocity material as expected in supernova ejecta. In addition, we find no unequivocal evidence of broad lines of alpha- and/or Fe-peak elements. The comparison with the absolute light curves of other interacting objects (including Type IIn supernovae) highlights the overall similarity with the prototypical impostor SN 1997bs. This supports our claim that SN 2007sv was not a genuine supernova, and was instead a supernova impostor, most likely similar to the major eruption of a luminous blue variable.
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