| 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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| 6. |
- Demeke, Mekonnen M., et al.
(författare)
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Development of a D-xylose fermenting and inhibitor tolerant industrial Saccharomyces cerevisiae strain with high performance in lignocellulose hydrolysates using metabolic and evolutionary engineering
- 2013
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Ingår i: Biotechnology for Biofuels. - : Springer Science and Business Media LLC. - 1754-6834. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Background: The production of bioethanol from lignocellulose hydrolysates requires a robust, D-xylose-fermenting and inhibitor-tolerant microorganism as catalyst. The purpose of the present work was to develop such a strain from a prime industrial yeast strain, Ethanol Red, used for bioethanol production. Results: An expression cassette containing 13 genes including Clostridium phytofermentans XylA, encoding D-xylose isomerase (XI), and enzymes of the pentose phosphate pathway was inserted in two copies in the genome of Ethanol Red. Subsequent EMS mutagenesis, genome shuffling and selection in D-xylose-enriched lignocellulose hydrolysate, followed by multiple rounds of evolutionary engineering in complex medium with D-xylose, gradually established efficient D-xylose fermentation. The best-performing strain, GS1.11-26, showed a maximum specific D-xylose consumption rate of 1.1 g/g DW/h in synthetic medium, with complete attenuation of 35 g/L D-xylose in about 17 h. In separate hydrolysis and fermentation of lignocellulose hydrolysates of Arundo donax (giant reed), spruce and a wheat straw/hay mixture, the maximum specific D-xylose consumption rate was 0.36, 0.23 and 1.1 g/g DW inoculum/h, and the final ethanol titer was 4.2, 3.9 and 5.8% (v/v), respectively. In simultaneous saccharification and fermentation of Arundo hydrolysate, GS1.11-26 produced 32% more ethanol than the parent strain Ethanol Red, due to efficient D-xylose utilization. The high D-xylose fermentation capacity was stable after extended growth in glucose. Cell extracts of strain GS1.11-26 displayed 17-fold higher XI activity compared to the parent strain, but overexpression of XI alone was not enough to establish D-xylose fermentation. The high D-xylose consumption rate was due to synergistic interaction between the high XI activity and one or more mutations in the genome. The GS1.11-26 had a partial respiratory defect causing a reduced aerobic growth rate. Conclusions: An industrial yeast strain for bioethanol production with lignocellulose hydrolysates has been developed in the genetic background of a strain widely used for commercial bioethanol production. The strain uses glucose and D-xylose with high consumption rates and partial cofermentation in various lignocellulose hydrolysates with very high ethanol yield. The GS1.11-26 strain shows highly promising potential for further development of an all-round robust yeast strain for efficient fermentation of various lignocellulose hydrolysates.
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| 7. |
- Harrison, Sandy P., et al.
(författare)
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Development and testing scenarios for implementing land use and land cover changes during the Holocene in Earth system model experiments
- 2020
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Ingår i: Geoscientific Model Development. - : Copernicus Gesellschaft MBH. - 1991-959X .- 1991-9603. ; 13:2, s. 805-824
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Tidskriftsartikel (refereegranskat)abstract
- Anthropogenic changes in land use and land cover (LULC) during the pre-industrial Holocene could have affected regional and global climate. Existing scenarios of LULC changes during the Holocene are based on relatively simple assumptions and highly uncertain estimates of population changes through time. Archaeological and palaeoenvironmental reconstructions have the potential to refine these assumptions and estimates. The Past Global Changes (PAGES) LandCover6k initiative is working towards improved reconstructions of LULC globally. In this paper, we document the types of archaeological data that are being collated and how they will be used to improve LULC reconstructions. Given the large methodological uncertainties involved, both in reconstructing LULC from the archaeological data and in implementing these reconstructions into global scenarios of LULC, we propose a protocol to evaluate the revised scenarios using independent pollen-based reconstructions of land cover and climate. Further evaluation of the revised scenarios involves carbon cycle model simulations to determine whether the LULC reconstructions are consistent with constraints provided by ice core records of CO2 evolution and modern-day LULC. Finally, the protocol outlines how the improved LULC reconstructions will be used in palaeoclimate simulations in the Palaeoclimate Modelling Intercomparison Project to quantify the magnitude of anthropogenic impacts on climate through time and ultimately to improve the realism of Holocene climate simulations.
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| 8. |
- Jung, Byeongju, et al.
(författare)
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Effects of episodic fluid flow on hydrocarbon migration in the Newport-Inglewood Fault Zone, Southern California
- 2014
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Ingår i: Geofluids. - : Wiley. - 1468-8115 .- 1468-8123. ; 14:2, s. 234-250
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Tidskriftsartikel (refereegranskat)abstract
- Fault permeability may vary through time due to tectonic deformations, transients in pore pressure and effective stress, and mineralization associated with water-rock reactions. Time-varying permeability will affect subsurface fluid migration rates and patterns of petroleum accumulation in densely faulted sedimentary basins such as those associated with the borderland basins of Southern California. This study explores the petroleum fluid dynamics of this migration. As a multiphase flow and petroleum migration case study on the role of faults, computational models for both episodic and continuous hydrocarbon migration are constructed to investigate large-scale fluid flow and petroleum accumulation along a northern section of the Newport-Inglewood fault zone in the Los Angeles basin, Southern California. The numerical code solves the governing equations for oil, water, and heat transport in heterogeneous and anisotropic geologic cross sections but neglects flow in the third dimension for practical applications. Our numerical results suggest that fault permeability and fluid pressure fluctuations are crucial factors for distributing hydrocarbon accumulations associated with fault zones, and they also play important roles in controlling the geologic timing for reservoir filling. Episodic flow appears to enhance hydrocarbon accumulation more strongly by enabling stepwise build-up in oil saturation in adjacent sedimentary formations due to temporally high pore pressure and high permeability caused by periodic fault rupture. Under assumptions that fault permeability fluctuate within the range of 1-1000 millidarcys (10(-15)-10(-12)m(2)) and fault pressures fluctuate within 10-80% of overpressure ratio, the estimated oil volume in the Inglewood oil field (approximately 450 million barrels oil equivalent) can be accumulated in about 24000years, assuming a seismically induced fluid flow event occurs every 2000years. This episodic petroleum migration model could be more geologically important than a continuous-flow model, when considering the observed patterns of hydrocarbons and seismically active tectonic setting of the Los Angeles basin.
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| 9. |
- Morrison, Kathleen D., et al.
(författare)
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Mapping past human land use using archaeological data : A new classification for global land use synthesis and data harmonization
- 2021
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 16:4
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Tidskriftsartikel (refereegranskat)abstract
- In the 12,000 years preceding the Industrial Revolution, human activities led to significant changes in land cover, plant and animal distributions, surface hydrology, and biochemical cycles. Earth system models suggest that this anthropogenic land cover change influenced regional and global climate. However, the representation of past land use in earth system models is currently oversimplified. As a result, there are large uncertainties in the current understanding of the past and current state of the earth system. In order to improve representation of the variety and scale of impacts that past land use had on the earth system, a global effort is underway to aggregate and synthesize archaeological and historical evidence of land use systems. Here we present a simple, hierarchical classification of land use systems designed to be used with archaeological and historical data at a global scale and a schema of codes that identify land use practices common to a range of systems, both implemented in a geospatial database. The classification scheme and database resulted from an extensive process of consultation with researchers worldwide. Our scheme is designed to deliver consistent, empirically robust data for the improvement of land use models, while simultaneously allowing for a comparative, detailed mapping of land use relevant to the needs of historical scholars. To illustrate the benefits of the classification scheme and methods for mapping historical land use, we apply it to Mesopotamia and Arabia at 6 kya (c. 4000 BCE). The scheme will be used to describe land use by the Past Global Changes (PAGES) LandCover6k working group, an international project comprised of archaeologists, historians, geographers, paleoecologists, and modelers. Beyond this, the scheme has a wide utility for creating a common language between research and policy communities, linking archaeologists with climate modelers, biodiversity conservation workers and initiatives.
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| 10. |
- Otterstedt, Karin, et al.
(författare)
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Switching the mode of metabolism in the yeast Saccharomyces cerevisiae.
- 2004
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Ingår i: Embro reports. - : EMBO. - 1469-221X .- 1469-3178. ; 5:5, s. 532-537
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Tidskriftsartikel (refereegranskat)abstract
- The biochemistry of most metabolic pathways is conserved from bacteria to humans, although the control mechanisms are adapted to the needs of each cell type. Oxygen depletion commonly controls the switch from respiration to fermentation. However, Saccharomyces cerevisiae also controls that switch in response to the external glucose level. We have generated an S. cerevisiae strain in which glucose uptake is dependent on a chimeric hexose transporter mediating reduced sugar uptake. This strain shows a fully respiratory metabolism also at high glucose levels as seen for aerobic organisms, and switches to fermentation only when oxygen is lacking. These observations illustrate that manipulating a single step can alter the mode of metabolism. The novel yeast strain is an excellent tool to study the mechanisms underlying glucose-induced signal transduction.
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| 11. |
- 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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