| 1. |
- 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. |
- Buchwitz, M., et al.
(författare)
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The GHG-CCI project of ESA's climate change initiative : Data products and application
- 2016
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Ingår i: Proceedings of Living Planet Symposium 2016. - 9789292213053 ; SP-740
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Konferensbidrag (refereegranskat)abstract
- The goal of the GHG-CCI project (http://www.esa-ghg-cci.org/) of ESA's Climate Change Initiative (CCI) is to generate global atmospheric satellite-derived carbon dioxide (CO2) and methane (CH4) data sets as needed to improve our understanding of the regional sources and sinks of these important greenhouse gases (GHG). Here we present an overview about the latest data set called Climate Research Data Package No. 3 (CRDP3). We focus on the GHG-CCI project core data products, which are near-surface-sensitive column-averaged dry air mole fractions of CO2 and CH4, denoted XCO2 (in ppm) and XCH4 (in ppb) retrieved from SCIAMACHY/ENVISAT (2002-2012) and TANSO-FTS/GOSAT (2009-today) nadir mode radiance observations in the near-infrared/shortwave-infrared spectral region. The GHG-CCI products are primarily individual sensor Level 2 products. However, we also generate merged Level 2 products ("EMMA products"). Here we also present a first GHG-CCI Level 3 product, namely XCO2 and XCH4 in Obs4MIPs format (monthly, 5°×5°).
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| 3. |
- Buchwitz, M., et al.
(författare)
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The greenhouse gas project of Esa's climate change initiative (GHG-CCI) : Overview, achievements and future plans
- 2015. - 7W3
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Ingår i: 2015 36th International Symposium on Remote Sensing of Environment. - 1682-1750. ; 40, s. 165-172
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Konferensbidrag (refereegranskat)abstract
- The GHG-CCI project (http://www.esa-ghg-cci.org/) is one of several projects of the European Space Agency's (ESA) Climate Change Initiative (CCI). The goal of the CCI is to generate and deliver data sets of various satellite-derived Essential Climate Variables (ECVs) in line with GCOS (Global Climate Observing System) requirements. The "ECV Greenhouse Gases" (ECV GHG) is the global distribution of important climate relevant gases-namely atmospheric CO2 and CH4-with a quality sufficient to obtain information on regional CO2 and CH4 sources and sinks. The main goal of GHG-CCI is to generate long-term highly accurate and precise time series of global near-surface-sensitive satellite observations of CO2 and CH4, i.e., XCO2 and XCH4, starting with the launch of ESA's ENVISAT satellite. These products are currently retrieved from SCIAMACHY/ENVISAT (2002-2012) and TANSO-FTS/GOSAT (2009-today) nadir mode observations in the near-infrared/shortwave-infrared spectral region. In addition, other sensors (e.g., IASI and MIPAS) and viewing modes (e.g., SCIAMACHY solar occultation) are also considered and in the future also data from other satellites. The GHG-CCI data products and related documentation are freely available via the GHG-CCI website and yearly updates are foreseen. Here we present an overview about the latest data set (Climate Research Data Package No. 2 (CRDP#2)) and summarize key findings from using satellite CO2 and CH4 retrievals to improve our understanding of the natural and anthropogenic sources and sinks of these important atmospheric greenhouse gases. We also shortly mention ongoing activities related to validation and initial user assessment of CRDP#2 and future plans.
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| 4. |
- Del Dotto, V., et al.
(författare)
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SSBP1 mutations cause mtDNA depletion underlying a complex optic atrophy disorder
- 2020
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Ingår i: Journal of Clinical Investigation. - : American Society for Clinical Investigation. - 0021-9738 .- 1558-8238. ; 130:1, s. 108-125
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Tidskriftsartikel (refereegranskat)abstract
- Inherited optic neuropathies include complex phenotypes, mostly driven by mitochondrial dysfunction. We report an optic atrophy spectrum disorder, including retinal macular dystrophy and kidney insufficiency leading to transplantation, associated with mitochondrial DNA (mtDNA) depletion without accumulation of multiple deletions. By whole-exome sequencing, we identified mutations affecting the mitochondrial single-strand binding protein (SSBP1) in 4 families with dominant and 1 with recessive inheritance. We show that SSBP1 mutations in patient-derived fibroblasts variably affect the amount of SSBP1 protein and alter multimer formation, but not the binding to ssDNA. SSBP1 mutations impaired mtDNA, nucleoids, and 7S-DNA amounts as well as mtDNA replication, affecting replisome machinery. The variable mtDNA depletion in cells was reflected in severity of mitochondrial dysfunction, including respiratory efficiency, OXPHOS subunits, and complex amount and assembly. mtDNA depletion and cytochrome c oxidase-negative cells were found ex vivo in biopsies of affected tissues, such as kidney and skeletal muscle. Reduced efficiency of mtDNA replication was also reproduced in vitro, confirming the pathogenic mechanism. Furthermore, ssbp1 suppression in zebrafish induced signs of nephropathy and reduced optic nerve size, the latter phenotype complemented by WT mRNA but not by SSBP1 mutant transcripts. This previously unrecognized disease of mtDNA maintenance implicates SSBP1 mutations as a cause of human pathology.
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| 5. |
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| 6. |
- van Heijningen, I, et al.
(författare)
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EASAPS/ESPRAS Considerations in getting back to work in Plastic Surgery with the COVID-19 Pandemic - A European point of view
- 2020
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Ingår i: Handchirurgie, Mikrochirurgie, plastische Chirurgie : Organ der Deutschsprachigen Arbeitsgemeinschaft fur Handchirurgie : Organ der Deutschsprachigen Arbeitsgemeinschaft fur Mikrochirurgie der Peripheren Nerven und Gefasse : Organ der V.... - : Georg Thieme Verlag KG. - 1439-3980. ; 52:044, s. 257-264
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this paper is to summarize the results of a consensus process and a European webinar of the two societies, European Association of Societies of Aesthetic Surgery (EASAPS) and the European Society of Plastic, Reconstructive and Aesthetic Societies (ESPRAS) on what is considered safe practice based on the scientific knowledge we have today. This review of the current situations gives considerations which have to be taken into account when getting back to work in plastic surgery with COVID-19 in Europe. At all times, one should be familiar the local and regional infection rates in the community, with particular emphasis on the emergence of second and third waves of the pandemic. Due to the fast-evolving nature of the COVID-19 pandemic the recommendations aim to be rather considerations than fixed guidelines and might need to be revised in near future.
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