| 1. |
- Balk, Lennart, et al.
(författare)
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Widespread episodic thiamine deficiency in Northern Hemisphere wildlife
- 2016
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)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. |
- Karlsson, Sofia, et al.
(författare)
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Ellagic acid inhibits lipopolysaccharide-induced expression of enzymes involved in the synthesis of prostaglandin E2 in human monocytes
- 2010
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Ingår i: British Journal of Nutrition. - : Cambridge University Press. - 0007-1145 .- 1475-2662. ; 103:8, s. 1102-1109
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Tidskriftsartikel (refereegranskat)abstract
- Ellagic acid, a natural polyphenol found in certain fruits, nuts and vegetables, has in recent years been the subject of intense research within the fields of cancer and inflammation. Pain, fever and swelling, all typical symptoms of inflammation, are ascribed to elevated levels of PGE(2). In the present study, we have investigated the effects of ellagic acid on PGE(2) release and on prostaglandin-synthesising enzymes in human monocytes. Ellagic acid was found to inhibit Ca ionophore A23187-, phorbol myristate acetate- and opsonised zymosan-induced release of PGE(2) from monocytes pre-treated with the inflammatory agent lipopolysaccharide. Ellagic acid suppressed the lipopolysaccharide-induced increase in protein expression of cyclo-oxygenase-2 (COX-2), microsomal PGE synthase-1 (mPGEs-1) and cytosolic phospholipase A(2)alpha (cPLA(2)alpha), while it had no effect on the constitutively expressed COX-1 protein. Ellagic acid had no apparent inhibitory effect on these enzymes when the activities were determined in cell-free assays. We conclude that the inhibitory effect of ellagic acid on PGE(2) release from monocytes is due to a suppressed expression of COX-2, mPGEs-1 and cPLA(2)alpha, rather than a direct effect on the activities of these enzymes.
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| 3. |
- Elmabsout, Ali Ateia, et al.
(författare)
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Cloning and Functional Studies of a Splice Variant of CYP26B1 Expressed in Vascular Cells
- 2012
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Ingår i: Plos One. - San Francisco, USA : Public Library of Science (PLoS). - 1932-6203. ; 7:5
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Tidskriftsartikel (refereegranskat)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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| 4. |
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| 5. |
- Saenz Mendez, Patricia
(författare)
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Chapter 14 - Multi-Target Drugs as Master Keys to Complex Diseases: Inverse Docking Strategies and Opportunities
- 2021
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Ingår i: Molecular Docking for Computer-Aided Drug Design. - : Academic Press. - 9780128223123 - 9780128223130 ; , s. 295-311
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- This chapter discusses the change in the paradigm of drug discovery, shifting from the “magic bullet” concept to the “magic shotgun” or “silver bullet” approach, i.e., one-compound—multiple-target model. The concept of polypharmacology and its aspects related to drug discovery and development, such as drug attrition and drug repurposing are presented. Computational multi-target drug design strategies are discussed, particularly focusing on docking approaches (forward and inverse) and by presenting relevant examples available in the literature.
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| 6. |
- Lupu, Diana, et al.
(författare)
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The ENDpoiNTs Project : Novel Testing Strategies for Endocrine Disruptors Linked to Developmental Neurotoxicity
- 2020
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 21:11
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Tidskriftsartikel (refereegranskat)abstract
- Ubiquitous exposure to endocrine-disrupting chemicals (EDCs) has caused serious concerns about the ability of these chemicals to affect neurodevelopment, among others. Since endocrine disruption (ED)-induced developmental neurotoxicity (DNT) is hardly covered by the chemical testing tools that are currently in regulatory use, the Horizon 2020 research and innovation action ENDpoiNTs has been launched to fill the scientific and methodological gaps related to the assessment of this type of chemical toxicity. The ENDpoiNTs project will generate new knowledge about ED-induced DNT and aims to develop and improve in vitro, in vivo, and in silico models pertaining to ED-linked DNT outcomes for chemical testing. This will be achieved by establishing correlative and causal links between known and novel neurodevelopmental endpoints and endocrine pathways through integration of molecular, cellular, and organismal data from in vitro and in vivo models. Based on this knowledge, the project aims to provide adverse outcome pathways (AOPs) for ED-induced DNT and to develop and integrate new testing tools with high relevance for human health into European and international regulatory frameworks.
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| 7. |
- Kumar, Vikash, et al.
(författare)
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Poplar carbohydrate-active enzymes : whole-genome annotation and functional analyses based on RNA expression data
- 2019
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Ingår i: The Plant Journal. - Hoboken : John Wiley & Sons. - 0960-7412 .- 1365-313X. ; 99:4, s. 589-609
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Tidskriftsartikel (refereegranskat)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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| 8. |
- Bohlin, Christina
(författare)
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In vitro and in vivo oxidation of diastereomers of lignin models of arylgylcerol b-aryl ether type and heterologous expression of laccase
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Enzymic and non-enzymic oxidation of lignin models of the arylglycerol β-aryl ether type was investigated in experiments aimed at providing a better understanding of the initial phase of biological lignin degradation. Product profiles and diasteromer selectivity were determined to gain knowledge of the properties of the oxidants and pave the way for evaluation of the presence of the oxidants in ligninolytic fungal cultures. Diastereomers of the non-phenolic lignin model 1-(3,4-dimethoxyphenyl)-2-(2-methoxyphenoxy)-1,3-propanediol (1) were oxidized in vitro with lignin peroxidase (LP), laccase-mediator systems, Fenton's reagent, cerium(IV) ammonium nitrate (CAN) and lead(IV) tetraacetate. The product profiles were found to be distinctive for the different oxidants, except for LP and CAN, which generated the same products in similar proportions. The reactions resulted in preferential degradation of the threo isomer, except for the Fenton's reagent reaction, which showed no stereo-preference, and the laccase reaction mediated by ABTS, which preferentially degraded the erythro isomer. Cultures of the white-rot fungi Trametes versicolor and Phanerochaete chrysosporium preferentially degraded the threo isomer of 1. This is not in agreement with the action of Fenton's reagent, since this oxidant does not exhibit any stereo-preference. Laccase from T. versicolor was expressed in Pichia pastoris and Aspergillus niger. Production of catalytically active T. versicolor laccase was achieved in both P. pastoris and A. niger using glyceraldehyde-3-phosphate dehydrogenase promoters. The level of laccase activity obtained with P. pastoris was significantly lower than that obtained with A. niger, but speed and convenience make the P. pastoris system attractive for screening purposes. A. niger produced high yields of heterologous laccase with properties similar to those of the native enzyme. A method was devised to purify laccase from cultures of A. niger. The method gave a 250-fold purification and a yield of >50%.
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