| 1. |
- Balk, Lennart, et al.
(author)
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Widespread episodic thiamine deficiency in Northern Hemisphere wildlife
- 2016
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In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 6
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Journal article (peer-reviewed)abstract
- Many wildlife populations are declining at rates higher than can be explained by known threats to biodiversity. Recently, thiamine (vitamin B-1) deficiency has emerged as a possible contributing cause. Here, thiamine status was systematically investigated in three animal classes: bivalves, ray-finned fishes, and birds. Thiamine diphosphate is required as a cofactor in at least five life-sustaining enzymes that are required for basic cellular metabolism. Analysis of different phosphorylated forms of thiamine, as well as of activities and amount of holoenzyme and apoenzyme forms of thiaminedependent enzymes, revealed episodically occurring thiamine deficiency in all three animal classes. These biochemical effects were also linked to secondary effects on growth, condition, liver size, blood chemistry and composition, histopathology, swimming behaviour and endurance, parasite infestation, and reproduction. It is unlikely that the thiamine deficiency is caused by impaired phosphorylation within the cells. Rather, the results point towards insufficient amounts of thiamine in the food. By investigating a large geographic area, by extending the focus from lethal to sublethal thiamine deficiency, and by linking biochemical alterations to secondary effects, we demonstrate that the problem of thiamine deficiency is considerably more widespread and severe than previously reported.
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| 2. |
- Elmabsout, Ali Ateia, et al.
(author)
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Cloning and Functional Studies of a Splice Variant of CYP26B1 Expressed in Vascular Cells
- 2012
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In: Plos One. - San Francisco, USA : Public Library of Science (PLoS). - 1932-6203. ; 7:5
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Journal article (peer-reviewed)abstract
- Background: All-trans retinoic acid (atRA) plays an essential role in the regulation of gene expression, cell growth and differentiation and is also important for normal cardiovascular development but may in turn be involved in cardiovascular diseases, i.e. atherosclerosis and restenosis. The cellular atRA levels are under strict control involving several cytochromes P450 isoforms (CYPs). CYP26 may be the most important regulator of atRA catabolism in vascular cells. The present study describes the molecular cloning, characterization and function of atRA-induced expression of a spliced variant of the CYP26B1 gene. Methodology/Principal Findings: The coding region of the spliced CYP26B1 lacking exon 2 was amplified from cDNA synthesized from atRA-treated human aortic smooth muscle cells and sequenced. Both the spliced variant and full length CYP26B1 was found to be expressed in cultured human endothelial and smooth muscle cells, and in normal and atherosclerotic vessel. atRA induced both variants of CYP26B1 in cultured vascular cells. Furthermore, the levels of spliced mRNA transcript were 4.5 times higher in the atherosclerotic lesion compared to normal arteries and the expression in the lesions was increased 20-fold upon atRA treatment. The spliced CYP26B1 still has the capability to degrade atRA, but at an initial rate one-third that of the corresponding full length enzyme. Transfection of COS-1 and THP-1 cells with the CYP26B1 spliced variant indicated either an increase or a decrease in the catabolism of atRA, probably depending on the expression of other atRA catabolizing enzymes in the cells. Conclusions/Significance: Vascular cells express the spliced variant of CYP26B1 lacking exon 2 and it is also increased in atherosclerotic lesions. The spliced variant displays a slower and reduced degradation of atRA as compared to the full-length enzyme. Further studies are needed, however, to clarify the substrate specificity and role of the CYP26B1 splice variant in health and disease.
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| 3. |
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| 4. |
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| 5. |
- Kumar, Vikash, et al.
(author)
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Poplar carbohydrate-active enzymes : whole-genome annotation and functional analyses based on RNA expression data
- 2019
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In: The Plant Journal. - Hoboken : John Wiley & Sons. - 0960-7412 .- 1365-313X. ; 99:4, s. 589-609
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Journal article (peer-reviewed)abstract
- Carbohydrate-active enzymes (CAZymes) catalyze the formation and modification of glycoproteins, glycolipids, starch, secondary metabolites and cell wall biopolymers. They are key enzymes for the biosynthesis of food and renewable biomass. Woody biomass is particularly important for long-term carbon storage and as an abundant renewable natural resource for many industrial applications. This study presents a re-annotation of CAZyme genes in the current Populus trichocarpa genome assembly and in silico functional characterization, based on high-resolution RNA-Seq data sets. Altogether, 1914 CAZyme and expansin genes were annotated in 101 families. About 1797 of these genes were found expressed in at least one Populus organ. We identified genes involved in the biosynthesis of different cell wall polymers and their paralogs. Whereas similar families exist in poplar and Arabidopsis thaliana (with the exception of CBM13 found only in poplar), a few families had significantly different copy numbers between the two species. To identify the transcriptional coordination and functional relatedness within the CAZymes and other proteins, we performed co-expression network analysis of CAZymes in wood-forming tissues using the AspWood database () for Populus tremula. This provided an overview of the transcriptional changes in CAZymes during the transition from primary to secondary wall formation, and the clustering of transcripts into potential regulons. Candidate enzymes involved in the biosynthesis of polysaccharides were identified along with many tissue-specific uncharacterized genes and transcription factors. These collections offer a rich source of targets for the modification of secondary cell wall biosynthesis and other developmental processes in woody plants.
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| 6. |
- Wu, Jingnan, 1994, et al.
(author)
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On the Conformation of Dimeric Acceptors and Their Polymer Solar Cells with Efficiency over 18 %
- 2023
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In: Angewandte Chemie International Edition. - : John Wiley & Sons. - 1433-7851 .- 1521-3773.
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Journal article (peer-reviewed)abstract
- The determination of molecular conformations of oligomeric acceptors (OAs) and their impact on molecular packing are crucial for understanding the photovoltaic performance of their resulting polymer solar cells (PSCs) but have not been well studied yet. Herein, we synthesized two dimeric acceptor materials, DIBP3F-Se and DIBP3F-S, which bridged two segments of Y6-derivatives by selenophene and thiophene, respectively. Theoretical simulation and experimental 1D and 2D NMR spectroscopic studies prove that both dimers exhibit O-shaped conformations other than S- or U-shaped counter-ones. Notably, this O-shaped conformation is likely governed by a distinctive "conformational lock" mechanism, arising from the intensified intramolecular & pi;-& pi; interactions among their two terminal groups within the dimers. PSCs based on DIBP3F-Se deliver a maximum efficiency of 18.09 %, outperforming DIBP3F-S-based cells (16.11 %) and ranking among the highest efficiencies for OA-based PSCs. This work demonstrates a facile method to obtain OA conformations and highlights the potential of dimeric acceptors for high-performance PSCs.
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| 7. |
- Saenz Mendez, Patricia, et al.
(author)
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Homology models of human all-trans retinoic acid metabolizing enzymes CYP26B1 and CYP26B1 spliced-variant.
- 2012
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In: Journal of Chemical Information and Modeling. - Washington, USA : American Chemical Society (ACS). - 1549-9596 .- 1549-960X. ; 52:10, s. 2631-2637
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Journal article (peer-reviewed)abstract
- Homology models of CYP26B1 (cytochrome P450RAI2) and CYP26B1 spliced variant were derived using the crystal structure of cyanobacterial CYP120A1 as template for the model building. The quality of the homology models generated were carefully evaluated, and the natural substrate all-trans-retinoic acid (atRA), several tetralone-derived retinoic acid metabolizing blocking agents (RAMBAs), and a well-known potent inhibitor of CYP26B1 (R115866) were docked into the homology model of full-length cytochrome P450 26B1. The results show that in the model of the full-length CYP26B1, the protein is capable of distinguishing between the natural substrate (atRA), R115866, and the tetralone derivatives. The spliced variant of CYP26B1 model displays a reduced affinity for atRA compared to the full-length enzyme, in accordance with recently described experimental information.
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| 8. |
- Alriksson, Björn, et al.
(author)
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Overexpression of Saccharomyces cerevisiae transcription factor and multidrug resistance genes conveys enhanced resistance to lignocellulose-derived fermentation inhibitors
- 2010
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In: Process Biochemistry. - : Elsevier. - 1359-5113 .- 1873-3298. ; 45:2, s. 264-271
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Journal article (peer-reviewed)abstract
- The presence of fermentation inhibitors in lignocellulose hydrolysates is an obstacle for achieving efficient fermentation of lignocellulose hydrolysates to ethanol and other commodities. In this investigation, the possibility of generating more inhibitor-resistant Saccharomyces cerevisiae by genetic engineering was explored. Based on previous results from studies of deletion mutants, three S. cerevisiae genes (ATR1, FLR1, YAP1) involved in multidrug resistance and stress response of yeast were selected for overexpression in three S. cerevisiae strains. The resistance of the transformed strains to lignocellulose-derived fermentation inhibitors and a dilute-acid spruce hydrolysate was evaluated in fermentation experiments. Overexpression of FLR1 resulted in enhanced resistance to the phenolic inhibitor coniferyl aldehyde and the furan aldehyde HMF (5-hydroxymethyl-2-furaldehyde). Overexpression of ATR1 conferred increased resistance to coniferyl aldehyde. Strains overexpressing YAP1, which encodes a transcription factor, displayed increased resistance to coniferyl aldehyde, HMF, and the spruce hydrolysate. An ethanol productivity of 0.17 g ethanol × l−1 × h−1 was achieved for a YAP1-overexpressing transformant cultivated in spruce hydrolysate, whereas a control transformant, which did not overexpress YAP1, only reached a productivity of 0.05 g ethanol × l−1 × h−1.
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| 9. |
- Arvidsson, Ann-Kristin, et al.
(author)
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Tyr-716 in the platelet-derived growth factor beta-receptor kinase insertis involved in GRB2 binding and Ras activation
- 1994
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In: Molecular and Cellular Biology. - : American Society for Microbiology. - 0270-7306 .- 1098-5549. ; 14:10, s. 6715-6726
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Journal article (peer-reviewed)abstract
- Ligand stimulation of the platelet-derived growth factor (PDGF) beta-receptor leads to activation of its intrinsic tyrosine kinase and autophosphorylation of the intracellular part of the receptor. The autophosphorylated tyrosine residues mediate interactions with downstream signal transduction molecules and thereby initiate different signalling pathways. A pathway leading to activation of the GTP-binding protein Ras involves the adaptor molecule GRB2. Here we show that Tyr-716, a novel autophosphorylation site in the PDGF beta-receptor kinase insert, mediates direct binding of GRB2 in vitro and in vivo. In a panel of mutant PDGF beta-receptors, in which Tyr-716 and the previously known autophosphorylation sites were individually mutated, only PDGFR beta Y716F failed to bind GRB2. Furthermore, a synthetic phosphorylated peptide containing Tyr-716 bound GRB2, and this peptide specifically interrupted the interaction between GRB2 and the wild-type receptor. In addition, the Y716(P) peptide significantly decreased the amount of GTP bound to Ras in response to PDGF in permeabilized fibroblasts as well as in porcine aortic endothelial cells expressing transfected PDGF beta-receptors. The mutant PDGFR beta Y716F still mediated activation of mitogen-activated protein kinases and an increased DNA synthesis in response to PDGF, indicating that multiple signal transduction pathways transduce mitogenic signals from the activated PDGF beta-receptor.
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| 10. |
- Bermúdez, Eduardo, et al.
(author)
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Improved homology model of cyclohexanone monooxygenase from Acinetobacter calcoaceticus based on multiple templates
- 2014
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In: Computational biology and chemistry. - : Elsevier BV. - 1476-9271 .- 1476-928X. ; 49, s. 14-22
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Journal article (peer-reviewed)abstract
- A new homology model of cyclohexanone monooxygenase (CHMO) from Acinetobacter calcoaceticus is derived based on multiple templates, and in particular the crystal structure of CHMO from Rhodococcus sp. The derived model was fully evaluated, showing that the quality of the new structure was improved over previous models. Critically, the nicotinamide cofactor is included in the model for the first time. Analysis of several molecular dynamics snapshots of intermediates in the enzymatic mechanism led to a description of key residues for cofactor binding and intermediate stabilization during the reaction, in particular Arg327 and the well known conserved motif (FxGxxxHxxxW) in Baeyer-Villiger monooxygenases, in excellent agreement with known experimental and computational data. © 2014 Elsevier Ltd.
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