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| 2. |
- Albrechtsen, A., et al.
(författare)
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Exome sequencing-driven discovery of coding polymorphisms associated with common metabolic phenotypes
- 2013
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 56:2, s. 298-310
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Tidskriftsartikel (refereegranskat)abstract
- Human complex metabolic traits are in part regulated by genetic determinants. Here we applied exome sequencing to identify novel associations of coding polymorphisms at minor allele frequencies (MAFs) > 1% with common metabolic phenotypes. The study comprised three stages. We performed medium-depth (8x) whole exome sequencing in 1,000 cases with type 2 diabetes, BMI > 27.5 kg/m(2) and hypertension and in 1,000 controls (stage 1). We selected 16,192 polymorphisms nominally associated (p < 0.05) with case-control status, from four selected annotation categories or from loci reported to associate with metabolic traits. These variants were genotyped in 15,989 Danes to search for association with 12 metabolic phenotypes (stage 2). In stage 3, polymorphisms showing potential associations were genotyped in a further 63,896 Europeans. Exome sequencing identified 70,182 polymorphisms with MAF > 1%. In stage 2 we identified 51 potential associations with one or more of eight metabolic phenotypes covered by 45 unique polymorphisms. In meta-analyses of stage 2 and stage 3 results, we demonstrated robust associations for coding polymorphisms in CD300LG (fasting HDL-cholesterol: MAF 3.5%, p = 8.5 x 10(-14)), COBLL1 (type 2 diabetes: MAF 12.5%, OR 0.88, p = 1.2 x 10(-11)) and MACF1 (type 2 diabetes: MAF 23.4%, OR 1.10, p = 8.2 x 10(-10)). We applied exome sequencing as a basis for finding genetic determinants of metabolic traits and show the existence of low-frequency and common coding polymorphisms with impact on common metabolic traits. Based on our study, coding polymorphisms with MAF above 1% do not seem to have particularly high effect sizes on the measured metabolic traits.
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| 4. |
- Daskoulidou, Nikoleta, et al.
(författare)
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High glucose enhances store-operated calcium entry by upregulating ORAI/STIM via calcineurin-NFAT signalling
- 2015
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Ingår i: Journal of Molecular Medicine. - : Springer Science and Business Media LLC. - 1432-1440 .- 0946-2716. ; 93:5, s. 511-521
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Tidskriftsartikel (refereegranskat)abstract
- ORAI and stromal interaction molecule (STIM) are storeoperated channel molecules that play essential roles in human physiology through a coupling mechanism of internal Ca2+ store to Ca2+ influx. However, the roles of ORAI and STIMin vascular endothelial cells under diabetic conditions remain unknown. Here, we investigated expression and signalling pathways of ORAI and STIM regulated by high glucose or hyperglycaemia using in vitro cell models, in vivo diabetic mice and tissues from patients. We found that ORAI1-3 and STIM1-2 were ubiquitously expressed in human vasculatures. Their expression was upregulated by chronic treatment with high glucose (HG, 25 mM D-glucose), which was accompanied by enhanced store-operated Ca2+ influx in vascular endothelial cells. The increased expression was also observed in the aortae from genetically modified Akita diabetic mice (C57BL/6-Ins2(Akita)/J) and streptozocin-induced diabetic mice, and aortae from diabetic patients. HG-induced upregulation of ORAI and STIM genes was prevented by the calcineurin inhibitor cyclosporin A and NFATc3 siRNA. Additionally, in vivo treatment with the nuclear factor of activated T cells (NFAT) inhibitor A-285222 prevented the gene upregulation in Akita mice. However, HG had no direct effects on ORAI1-3 currents and the channel activation process through cytosolic STIM1 movement in the cells coexpressing STIM1-EYFP/ORAIs. We concluded that upregulation of STIM/ORAI through Ca2+-calcineurin-NFAT pathway is a novel mechanism causing abnormal Ca2+ homeostasis and endothelial dysfunction under hyperglycaemia.
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| 5. |
- Hu, Xia-lin, et al.
(författare)
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Evaluating the impacts of some environmentally relevant factors on the availability of bisphenol A with negligible-depletion SPME
- 2006
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Ingår i: Chemosphere. - : Elsevier BV. - 1879-1298 .- 0045-6535. ; 65:11, s. 1935-1941
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Tidskriftsartikel (refereegranskat)abstract
- The effect of some environmentally relevant factors including salinity, pH, and humic acids on the availability of bisphenol A (BPA) was evaluated by using the negligible-depletion solid-phase microextraction (nd-SPME) biomimetic method. With the variation of salinity (0-500 mM NaCl) and pH (5.0-8.5) of aqueous solutions, the partition coefficients of BPA between the nd-SPME fiber and the aqueous solution varied in the range of logD = 3.55-3.86, which indicates that the salinity and pH can influence the availability of BPA. By using Acros humic acid as model dissolved organic matter (DOM), it was also demonstrated that the environmental factors such as salinity and pH could affect the partitioning of BPA between DOM and aqueous solutions. The determined partition coefficients of BPA between dissolved organic carbon (DOC) and aqueous solutions were in the range of log D-DOC = 4.03-5.60 for Acros humic acid solutions with 1-50 mg l(-1) DOC. The influence of salinity and pH on log D-DOC was more significant at low concentration (0-5 mg l(-1)) of DOC. (c) 2006 Elsevier Ltd. All rights reserved.
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| 6. |
- Ji, Xuemei, et al.
(författare)
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Identification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk
- 2018
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 9, s. 1-15
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) identified the chromosome 15q25.1 locus as a leading susceptibility region for lung cancer. However, the pathogenic pathways, through which susceptibility SNPs within chromosome 15q25.1 affects lung cancer risk, have not been explored. We analyzed three cohorts with GWAS data consisting 42,901 individuals and lung expression quantitative trait loci (eQTL) data on 409 individuals to identify and validate the underlying pathways and to investigate the combined effect of genes from the identified susceptibility pathways. The KEGG neuroactive ligand receptor interaction pathway, two Reactome pathways, and 22 Gene Ontology terms were identified and replicated to be significantly associated with lung cancer risk, with P values less than 0.05 and FDR less than 0.1. Functional annotation of eQTL analysis results showed that the neuroactive ligand receptor interaction pathway and gated channel activity were involved in lung cancer risk. These pathways provide important insights for the etiology of lung cancer.
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| 7. |
- Jiang, Liying, et al.
(författare)
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Abiotic synthesis of amino acids and self-crystallization under prebiotic conditions
- 2014
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Building on previous research on the origin and homochirality of life, this study focuses on analyses profiling important building blocks of life: the natural amino acids. The spark discharge variation of the iconic Miller experiment was performed with a reducing gas mixture of ammonia, methane, water and hydrogen. Amino acid analysis using liquid chromatography coupled with tandem mass spectrometry after pre-column derivatizaiton revealed the generation of several amino acids including those essential for life. Re-crystallization of the synthetic products and enantiomeric ratio analysis were subsequently performed. Results from liquid chromatography coupled with either fluorescent detector or tandem mass spectrometry after pre-column derivatization with chiral reagent revealed spontaneous and effective asymmetric resolution of serine and alanine. This work describes a useful analytical platform for investigation of hypotheses regarding the origin and homochirality of amino acids under prebiotic conditions. The formation of numerous amino acids in the electric discharge experiment and the occurrence of high enantiomeric ratios of amino acids in re-crystallization experiment give valuable implications for future studies in unraveling fundamental questions regarding origins and evolution of life.
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| 8. |
- Liu, Jing-fu, et al.
(författare)
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Equilibrium sampling of freely dissolved alkylphenols into a thin film of 1-octanol supported on a hollow fiber membrane
- 2006
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 1520-6882 .- 0003-2700. ; 78:24, s. 8526-8534
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Tidskriftsartikel (refereegranskat)abstract
- A new negligible depletion extraction procedure was proposed for equilibrium sampling of 4-tert-octylphenol (OP) and 4-nonylphenol (NP) into a thin film of 1-octanol supported on a hollow fiber membrane. This thin liquid film extraction technique was directed at the determination of ( 1) freely dissolved concentrations, ( 2) distribution coefficients to 1-octanol (D-ow), and ( 3) binding to dissolved organic matter (D-DOC). The sampling device was prepared by dipping pieces of polypropylene microporous hollow fiber membrane (10-mm length, 30-mu m wall thickness, 240-mu m inner diameter) into 1-octanol for a few seconds to impregnate the pores of the hollow fiber wall. After stirring in 100 mL of sample solution for 24 h, the sampling device was harvested and desorbed with 30 mu L of methanol, of which 20 mu L was injected for HPLC analysis. With the measured Dow of a chemical and its equilibrium concentration in the 1-octanol sampling phase (C-octanol), the freely dissolved concentration (C-free) was calibrated based on C-free = C-octanol/D-ow. Measured log D-ow values of OP (4.32 +/- 0.06) and NP (4.79 +/- 0.02) were independent of the chemical concentration, only minimally affected by the environmentally relevant pH, buffering capacity, and salinity of samples, and agreed well with reported values. Log D-DOC values of OP (4.89 +/- 0.43) and NP (5.14 +/- 0.37), determined in Aldrich humic acid solution, agreed with reported partition coefficients to organic carbon ( log K-oc) for particles in river water and effluent wastewater. Short equilibration times and high enrichment factors were obtained for both analytes due to the high surface to volume ratio of the new sampler. The technique was successfully applied to determine C-free of OP and NP in real water samples and to study their association with humic acids and bovine albumin.
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| 9. |
- Liu, Wei, et al.
(författare)
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Impact of silver nanoparticles on human cells : effect of particle size
- 2010
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Ingår i: Nanotoxicology. - New York : Informa Healthcare. - 1743-5390 .- 1743-5404. ; 4:3, s. 319-330
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Tidskriftsartikel (refereegranskat)abstract
- This work investigated the cytotoxicities of three silver nanoparticles (SNPs) SNP-5, SNP-20 and SNP-50 with different sizes ( approximately 5 nm, approximately 20 nm and approximately 50 nm) using four human cell models (A549, SGC-7901, HepG2 and MCF-7). Endpoints included cell morphology, cell viability, cellular membrane integrity, oxidative stress and cell cycle progression. Observable deleterious effects on the cell morphologies and membrane integrity were induced by SNP-5 and SNP-20. SNPs elevated the ROS levels in cells and arrested the cells at S phase. Apoptosis occurred for 4-9% of the exposed cells. All these cellular responses as well as EC50 values were found to be size-dependent for the tested SNPs. Ultrastructural observations confirmed the presence of SNPs inside cells. Elemental analysis of silver in cells by ICP-MS showed that smaller nanoparticles enter cells more easily than larger ones, which may be the cause of higher toxic effects. The findings may assist in the design of SNP applications and provide insights into their toxicity.
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| 10. |
- Lui, Gui Qun, et al.
(författare)
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Sintering characteristics of BCSAF cement clinker with added wastes from production of manganese and magnesium metals
- 2017
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Ingår i: Advances in Cement Research. - : Institution of Civil Engineers (ICE). - 0951-7197 .- 1751-7605. ; 29:6, s. 227-235
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Tidskriftsartikel (refereegranskat)abstract
- The production of belite-calcium sulfoaluminate-ferrite (BCSAF) cement with the addition of industrial wastes as feedstock has been studied for many years. The preparation of clinkers is essential in cement production, in which all raw materials react with each other to generate key phases in cement under some specified conditions. The objective of this study was to investigate the sintering characteristics of BCSAF cement clinkers. Four BCSAF clinkers with different compositions were examined. High-temperature microscopy, quantitative x-ray powder diffraction analysis and scanning electron microscopy were used to analyse sintering features and phase composition. The results show that the use of wastes from the production of manganese and magnesium metals, which were added to the raw materials to make clinker pellets, can significantly reduce the firing temperature of BCSAF clinker. The firing temperatures of clinkers with added wastes were below 1300°C, much lower than the temperature used for conventional Portland cement (1450°C). The ferrite phase was always found to inter-grow with the C4A3S¯">C 4 A 3 S ¯ C4A3S¯ phase or C2AS phase, just like the interstitial phase. The ferrite phase acted as a solid solution during cement sintering. A small quantity of iron oxide can make the clinker more porous, leading to energy savings in subsequent grinding processes.
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