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- Wiessner, M., et al.
(författare)
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Biallelic variants in HPDL cause pure and complicated hereditary spastic paraplegia
- 2021
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Ingår i: Brain : a journal of neurology. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 144:5, s. 1422-1434
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Tidskriftsartikel (refereegranskat)abstract
- Human 4-hydroxyphenylpyruvate dioxygenase-like (HPDL) is a putative iron-containing non-heme oxygenase of unknown specificity and biological significance. We report 25 families containing 34 individuals with neurological disease associated with biallelic HPDL variants. Phenotypes ranged from juvenile-onset pure hereditary spastic paraplegia to infantile-onset spasticity and global developmental delays, sometimes complicated by episodes of neurological and respiratory decompensation. Variants included bona fide pathogenic truncating changes, although most were missense substitutions. Functionality of variants could not be determined directly as the enzymatic specificity of HPDL is unknown; however, when HPDL missense substitutions were introduced into 4-hydroxyphenylpyruvate dioxygenase (HPPD, an HPDL orthologue), they impaired the ability of HPPD to convert 4-hydroxyphenylpyruvate into homogentisate. Moreover, three additional sets of experiments provided evidence for a role of HPDL in the nervous system and further supported its link to neurological disease: (i) HPDL was expressed in the nervous system and expression increased during neural differentiation; (ii) knockdown of zebrafish hpdl led to abnormal motor behaviour, replicating aspects of the human disease; and (iii) HPDL localized to mitochondria, consistent with mitochondrial disease that is often associated with neurological manifestations. Our findings suggest that biallelic HPDL variants cause a syndrome varying from juvenile-onset pure hereditary spastic paraplegia to infantile-onset spastic tetraplegia associated with global developmental delays. © 2021 The Author(s).
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- Abbadessa, G, et al.
(författare)
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Unsung hero Robert C. Gallo
- 2009
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 323:5911, s. 206-207
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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- Von Clarmann, T., et al.
(författare)
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A blind test retrieval experiment for infrared limb emission spectrometry
- 2003
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Ingår i: Journal of Geophysical Research - Atmospheres. - 2169-897X .- 2169-8996. ; 108:D23
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Tidskriftsartikel (refereegranskat)abstract
- The functionality and characteristics of six different data processors (i.e., retrieval codes in their actual software and hardware environment) for analysis of high-resolution limb emission infrared spectra recorded by the space-borne Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) have been validated by means of a blind test retrieval experiment based on synthetic spectra. For this purpose a self-consistent set of atmospheric state parameters, including pressure, temperature, vibrational temperatures, and abundances of trace gases and aerosols, has been generated and used as input for radiative transfer calculations for MIPAS measurement geometry and configuration. These spectra were convolved with the MIPAS field of view, spectrally degraded by the MIPAS instrument line shape, and, finally, superimposed with synthetic measurement noise. These synthetic MIPAS measurements were distributed among the participants of the project “Advanced MIPAS level-2 data analysis” (AMIL2DA), who performed temperature and species abundance profile retrievals by inverse radiative transfer calculations. While the retrieved profiles of atmospheric state parameters reflect some characteristics of the individual data processors, it was shown that all the data processors under investigation are capable of producing reliable results in the sense that deviations of retrieved results from the reference profiles are within the margin that is consistent with analytical error estimation.
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