| 1. |
- Anderson, Christopher D., et al.
(författare)
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Common Variants Within Oxidative Phosphorylation Genes Influence Risk of Ischemic Stroke and Intracerebral Hemorrhage
- 2013
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Ingår i: Stroke: a journal of cerebral circulation. - 1524-4628. ; 44:3, s. 612-619
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose-Previous studies demonstrated association between mitochondrial DNA variants and ischemic stroke (IS). We investigated whether variants within a larger set of oxidative phosphorylation (OXPHOS) genes encoded by both autosomal and mitochondrial DNA were associated with risk of IS and, based on our results, extended our investigation to intracerebral hemorrhage (ICH). Methods-This association study used a discovery cohort of 1643 individuals, a validation cohort of 2432 individuals for IS, and an extension cohort of 1476 individuals for ICH. Gene-set enrichment analysis was performed on all structural OXPHOS genes, as well as genes contributing to individual respiratory complexes. Gene-sets passing gene-set enrichment analysis were tested by constructing genetic scores using common variants residing within each gene. Associations between each variant and IS that emerged in the discovery cohort were examined in validation and extension cohorts. Results-IS was associated with genetic risk scores in OXPHOS as a whole (odds ratio [OR], 1.17; P=0.008) and complex I (OR, 1.06; P=0.050). Among IS subtypes, small vessel stroke showed association with OXPHOS (OR, 1.16; P=0.007), complex I (OR, 1.13; P=0.027), and complex IV (OR, 1.14; P=0.018). To further explore this small vessel association, we extended our analysis to ICH, revealing association between deep hemispheric ICH and complex IV (OR, 1.08; P=0.008). Conclusions-This pathway analysis demonstrates association between common genetic variants within OXPHOS genes and stroke. The associations for small vessel stroke and deep ICH suggest that genetic variation in OXPHOS influences small vessel pathobiology. Further studies are needed to identify culprit genetic variants and assess their functional consequences. (Stroke. 2013;44:612-619.)
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| 2. |
- Burdett, Heidi L., et al.
(författare)
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Spatiotemporal Variability of Dimethylsulphoniopropionate on a Fringing Coral Reef : The Role of Reefal Carbonate Chemistry and Environmental Variability
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 8:5
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Tidskriftsartikel (refereegranskat)abstract
- Oceanic pH is projected to decrease by up to 0.5 units by 2100 (a process known as ocean acidification, OA), reducing the calcium carbonate saturation state of the oceans. The coastal ocean is expected to experience periods of even lower carbonate saturation state because of the inherent natural variability of coastal habitats. Thus, in order to accurately project the impact of OA on the coastal ocean, we must first understand its natural variability. The production of dimethylsulphoniopropionate (DMSP) by marine algae and the release of DMSP's breakdown product dimethylsulphide (DMS) are often related to environmental stress. This study investigated the spatiotemporal response of tropical macroalgae (Padina sp., Amphiroa sp. and Turbinaria sp.) and the overlying water column to natural changes in reefal carbonate chemistry. We compared macroalgal intracellular DMSP and water column DMSP+DMS concentrations between the environmentally stable reef crest and environmentally variable reef flat of the fringing Suleman Reef, Egypt, over 45-hour sampling periods. Similar diel patterns were observed throughout: maximum intracellular DMSP and water column DMS/P concentrations were observed at night, coinciding with the time of lowest carbonate saturation state. Spatially, water column DMS/P concentrations were highest over areas dominated by seagrass and macroalgae (dissolved DMS/P) and phytoplankton (particulate DMS/P) rather than corals. This research suggests that macroalgae may use DMSP to maintain metabolic function during periods of low carbonate saturation state. In the reef system, seagrass and macroalgae may be more important benthic producers of dissolved DMS/P than corals. An increase in DMS/P concentrations during periods of low carbonate saturation state may become ecologically important in the future under an OA regime, impacting larval settlement and increasing atmospheric emissions of DMS.
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| 3. |
- Ezzat, Kariem, et al.
(författare)
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PepFect 14, a novel cell-penetrating peptide for oligonucleotide delivery in solution and as solid formulation
- 2011
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 39:12, s. 5284-5298
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Tidskriftsartikel (refereegranskat)abstract
- Numerous human genetic diseases are caused by mutations that give rise to aberrant alternative splicing. Recently, several of these debilitating disorders have been shown to be amenable for splice-correcting oligonucleotides (SCOs) that modify splicing patterns and restore the phenotype in experimental models. However, translational approaches are required to transform SCOs into usable drug products. In this study, we present a new cell-penetrating peptide, PepFect14 (PF14), which efficiently delivers SCOs to different cell models including HeLa pLuc705 and mdx mouse myotubes; a cell culture model of Duchenne's muscular dystrophy (DMD). Non-covalent PF14-SCO nanocomplexes induce splice-correction at rates higher than the commercially available lipid-based vector Lipofectamine™ 2000 (LF2000) and remain active in the presence of serum. Furthermore, we demonstrate the feasibility of incorporating this delivery system into solid formulations that could be suitable for several therapeutic applications. Solid dispersion technique is utilized and the formed solid formulations are as active as the freshly prepared nanocomplexes in solution even when stored at an elevated temperatures for several weeks. In contrast, LF2000 drastically loses activity after being subjected to same procedure. This shows that using PF14 is a very promising translational approach for the delivery of SCOs in different pharmaceutical forms.
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| 4. |
- Gaber, Yasser, et al.
(författare)
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An investigation of enzymatic kinetic resolution of racemic clopidogrel
- 2014
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Ingår i: Asian Journal of Microbiology, Biotechnology and Environmental Sciences. ; 16:2, s. 247-251
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents a biocatalysis based approach for asymmetric hydrolysis of Clopidogrel, one of the most effective antiplatelet aggregators. Instead of the conventional "wet lab" screening method, we used an advanced chemical information retrieval tool, Scifinder®, to find suitable enzyme candidate(s) for the asymmetric hydrolysis. Scifinder® search for reactions similar to the target reaction retrieved three potential hits: horse liver esterase, chymotrypsin and Candida rugosa lipase. Among the three, horse liver esterase was experimentally found to hydrolyse the correct isomer (R) of the racemic clopidogrel. Investigation of the effect of different water miscible co-solvents showed DMSO to provide the highest enantiomeric excess (ee) value of 20% at 43% conversion of the racemic ester, while a dicyanamide based ionic liquid as a co-solvent showed 12% ee. This article demonstrates the potential of the chemical databases as a possible rapid, resource-efficient tool to find an appropriate selective biocatalyst.
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| 5. |
- Gaber, Yasser, et al.
(författare)
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HPLC-EAT (Environmental Assessment Tool): A tool for profiling safety, health and environmental impacts of liquid chromatography methods
- 2011
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Ingår i: Green Chemistry. - : Royal Society of Chemistry (RSC). - 1463-9270 .- 1463-9262. ; 13:8, s. 2021-2025
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Tidskriftsartikel (refereegranskat)abstract
- A simple and efficient approach for profiling the greenness of high performance liquid chromatography (HPLC) methods is presented. This environmental assessment tool (EAT) takes into consideration the environmental, health and safety issues for all solvents involved in the chromatographic method, and calculates a total score that can be used for comparison of the greenness of different methods. A software, HPLC-EAT, has been designed to facilitate the calculation and can be downloaded free of charge at http://www.biotek.lu.se/hplc-eat/. HPLC-EAT was successfully applied for a set of different HPLC methods from the literature, including both analytical and preparative chromatography. The performance of the tool was validated and it was further combined with another free software Eco-solvent tool to perform life cycle assessments of waste disposal options of distillation or incineration. HPLC-EAT can be routinely used in method development to calculate the greenness beside the conventional standards of accuracy, robustness and reproducibility.
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