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排序方式: 共有171条查询结果,搜索用时 15 毫秒
21.
Dorina Ibi Manon Boot Martijn E.T. Dollé J. Wouter Jukema Frits R. Rosendaal Constantinos Christodoulides Matt J. Neville Robert Koivula Patrick C.N. Rensen Fredrik Karpe Raymond Noordam Ko Willems van Dijk 《Journal of lipid research》2022,63(5):100193
Triglyceride (TG)-lowering LPL variants in combination with genetic LDL-C-lowering variants are associated with reduced risk of coronary artery disease (CAD). Genetic variation in the APOA5 gene encoding apolipoprotein A-V also strongly affects TG levels, but the potential clinical impact and underlying mechanisms are yet to be resolved. Here, we aimed to study the effects of APOA5 genetic variation on CAD risk and plasma lipoproteins through factorial genetic association analyses. Using data from 309,780 European-ancestry participants from the UK Biobank, we evaluated the effects of lower TG levels as a result of genetic variation in APOA5 and/or LPL on CAD risk with or without a background of reduced LDL-C. Next, we compared lower TG levels via APOA5 and LPL variation with over 100 lipoprotein measurements in a combined sample from the Netherlands Epidemiology of Obesity study (N = 4,838) and the Oxford Biobank (N = 6,999). We found that lower TG levels due to combined APOA5 and LPL variation and genetically-influenced lower LDL-C levels afforded the largest reduction in CAD risk (odds ratio: 0.78 (0.73–0.82)). Compared to patients with genetically-influenced lower TG via LPL, genetically-influenced lower TG via APOA5 had similar and independent, but notably larger, effects on the lipoprotein profile. Our results suggest that lower TG levels as a result of APOA5 variation have strong beneficial effects on CAD risk and the lipoprotein profile, which suggest apo A-V may be a potential novel therapeutic target for CAD prevention. 相似文献
22.
Rosa van den Berg Sander Kooijman Raymond Noordam Ashna Ramkisoensing Gustavo Abreu-Vieira Lauren L. Tambyrajah Wieneke Dijk Philip Ruppert Isabel M. Mol Barbara Kramar Rosanna Caputo Laura Sardón Puig Evelien M. de Ruiter Jan Kroon Menno Hoekstra Ronald J. van der Sluis Onno C. Meijer Ko Willems van Dijk Patrick C.N. Rensen 《Cell reports》2018,22(13):3521-3533
23.
Linker length and composition influence the flexibility of Oct-1 DNA binding. 总被引:5,自引:1,他引:4 下载免费PDF全文
H C van Leeuwen M J Strating M Rensen W de Laat P C van der Vliet 《The EMBO journal》1997,16(8):2043-2053
24.
Role of bicarbonate in photosystem II, the water-plastoquinone oxido-reductase of plant photosynthesis 总被引:4,自引:0,他引:4
Depletion of bicarbonate (carbon dioxide) from oxygenic cells or organelles not only causes cessation of carbon dioxide fixation, but also a strong decrease in the activity of photosystem II; the photosystem II activity can be restored by readdition of bicarbonate. Effects of bicarbonate exist on both the acceptor as well as on the donor side of photosystem II. The influence on the acceptor side is located between the primary and secondary quinone electron acceptor of photosystem II, and can be demonstrated in intact cells or leaves as well as in isolated thylakoids and reaction center preparations. At physiological pH, bicarbonate ions are suggested to form hydrogen bonds to several amino acids on both D1 and D2 proteins, the reaction center subunits of photosystem II, as well as to form ligands to the non-heme iron between the D1 and D2 proteins. Bicarbonate, at physiological pH, has an important role in the water-plastoquinone oxido-reductase: on the one hand it may stabilize, by conformational means, the reaction center protein of photosystem II that allows efficient electron flow and protonation of certain amino acids near the secondary quinone electron acceptor of photosystem II; and, on the other hand, it akppears to play a significant role in the assembly or functioning of the manganese complex at the donor side. Functional roles of bicarbonate in vivo, including protection against photoinhibition, are also discussed. 相似文献
25.
Maaike Schilperoort Jan Kroon Sander Kooijman Annelies E. Smit Max Gentenaar Kathrin Mletzko Felix N. Schmidt Leo van Ruijven Bjrn Busse Alberto M. Pereira Natasha M. AppelmanDijkstra Nathalie Bravenboer Patrick C.N. Rensen Onno C. Meijer Elizabeth M. Winter 《Aging cell》2021,20(10)
Glucocorticoid (GC)‐induced osteoporosis is a widespread health problem that is accompanied with increased fracture risk. Detrimental effects of anti‐inflammatory GC therapy on bone have been ascribed to the excess in GC exposure, but it is unknown whether there is also a role for disruption of the endogenous GC rhythm that is inherent to GC therapy. To investigate this, we implanted female C57Bl/6J mice with slow‐release corticosterone (CORT) pellets to blunt the rhythm in CORT levels without inducing hypercortisolism. Flattening of CORT rhythm reduced cortical and trabecular bone volume and thickness, whilst bone structure was maintained in mice injected with supraphysiologic CORT at the time of their endogenous GC peak. Mechanistically, mice with a flattened CORT rhythm showed disrupted circadian gene expression patterns in bone, along with changes in circulating bone turnover markers indicative of a negative balance in bone remodelling. Indeed, double calcein labelling of bone in vivo revealed a reduced bone formation in mice with a flattened CORT rhythm. Collectively, these perturbations in bone turnover and structure decreased bone strength and stiffness, as determined by mechanical testing. In conclusion, we demonstrate for the first time that flattening of the GC rhythm disrupts the circadian clock in bone and results in an osteoporotic phenotype in mice. Our findings indicate that at least part of the fracture risk associated with GC therapy may be the consequence of a disturbed GC rhythm, rather than excess GC exposure alone, and that a dampened GC rhythm may contribute to the age‐related risk of osteoporosis. 相似文献
26.
彩色豆马勃子实体的化感作用及其化感物质的分离鉴定 总被引:13,自引:2,他引:11
彩色豆马勃能与松树、桉树形成外生菌根,研究其次生代谢产物对植物的影响具有重要意义。用水、乙醇和丙酮抽提彩色豆马勃的子实体,发现这些抽提物对稗草和水稻幼苗生长有极显着的抑制作用。丙酮抽提物对狼尾草和油菜幼苗生长有抑制作用。子实体的丙酮抽提物用硅胶柱色谱分离得到2个纯化合物,可鉴定为豆马勃内酯(Pisolactone)和麦角甾醇。该2个化合物在400μg·ml-1浓度下均显着抑制稗草幼苗根生长。豆马勃内酯在100μg·ml-1浓度下仍然极显着抑制稗草幼苗根生长. 相似文献
27.
Proteolytic Processing of the Open Reading Frame 1b-Encoded Part of Arterivirus Replicase Is Mediated by nsp4 Serine Protease and Is Essential for Virus Replication 总被引:10,自引:3,他引:7 下载免费PDF全文
Leonie C. van Dinten Sietske Rensen Alexander E. Gorbalenya Eric J. Snijder 《Journal of virology》1999,73(3):2027-2037
The open reading frame (ORF) 1b-encoded part of the equine arteritis virus (EAV) replicase is expressed by ribosomal frameshifting during genome translation, which results in the production of an ORF1ab fusion protein (345 kDa). Four ORF1b-encoded processing products, nsp9 (p80), nsp10 (p50), nsp11 (p26), and nsp12 (p12), have previously been identified in EAV-infected cells (L. C. van Dinten, A. L. M. Wassenaar, A. E. Gorbalenya, W. J. M. Spaan, and E. J. Snijder, J. Virol. 70:6625–6633, 1996). In the present study, the generation of these four nonstructural proteins was shown to be mediated by the nsp4 serine protease, which is the main viral protease (E. J. Snijder, A. L. M. Wassenaar, L. C. van Dinten, W. J. M. Spaan, and A. E. Gorbalenya, J. Biol. Chem. 271:4864–4871, 1996). Mutagenesis of candidate cleavage sites revealed that Glu-2370/Ser, Gln-2837/Ser, and Glu-3056/Gly are the probable nsp9/10, nsp10/11, and nsp11/12 junctions, respectively. Mutations which abolished ORF1b protein processing were introduced into a recently developed infectious cDNA clone (L. C. van Dinten, J. A. den Boon, A. L. M. Wassenaar, W. J. M. Spaan, and E. J. Snijder, Proc. Natl. Acad. Sci. USA 94:991–997, 1997). An analysis of these mutants showed that the selective blockage of ORF1b processing affected different stages of EAV reproduction. In particular, the mutant with the nsp10/11 cleavage site mutation Gln-2837→Pro displayed an unusual phenotype, since it was still capable of RNA synthesis but was incapable of producing infectious virus. 相似文献
28.
Improving crop nutrient ef ficiency becomes an essential consideration for environmentally friendly and sustainable agriculture. Plant growth and development is dependent on 17 essential nutrient elements,among them,nitrogen(N) and phosphorus(P) are the two most important mineral nutrients. Hence it is not surprising that low N and/or low P availability in soils severely constrains crop growth and productivity,and thereby have become high priority targets for improving nutrient ef ficiency in crops. Root exploration largely determines the ability of plants to acquire mineral nutrients from soils. Therefore,root architecture,the 3-dimensional con figuration of the plant's root system in the soil,is of great importance for improving crop nutrient ef ficiency. Furthermore,the symbiotic associations between host plants and arbuscular mycorrhiza fungi/rhizobial bacteria,are additional important strategies to enhance nutrient acquisition. In this review,we summarize the recent advances in the current understanding of crop species control of root architecture alterations in response to nutrient availability and root/microbe symbioses,through gene or QTL regulation,which results in enhanced nutrient acquisition. 相似文献
29.
Willeke de Haan Jitske de Vries-van der Weij Isabel M. Mol Menno Hoekstra Johannes A. Romijn J. Wouter Jukema Louis M. Havekes Hans M.G. Princen Patrick C.N. Rensen 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2009,1791(3):191-197
Pregnane X receptor (PXR) agonism has been shown to affect multiple steps in both the synthesis and catabolism of HDL, but its integrated effect on HDL metabolism in vivo remains unclear. The aim of this study was to evaluate the net effect of PXR agonism on HDL metabolism in ApoE?3-Leiden (E3L) and E3L.CETP mice, well-established models for human-like lipoprotein metabolism. Female mice were fed a diet with increasing amounts of the potent PXR agonist 5-pregnen-3β-ol-20-one-16α-carbonitrile (PCN). In E3L and E3L.CETP mice, PCN increased liver lipids as well as plasma cholesterol and triglycerides. However, whereas PCN increased cholesterol contained in large HDL-1 particles in E3L mice, it dose-dependently decreased HDL-cholesterol in E3L.CETP mice, indicating that CETP expression dominates the effect of PCN on HDL metabolism. Analysis of the hepatic expression of genes involved in HDL metabolism showed that PCN decreased expression of genes involved in HDL synthesis (Abca1, Apoa1), maturation (Lcat, Pltp) and clearance (Sr-b1). The HDL-increasing effect of PCN, observed in E3L mice, is likely caused by a marked decrease in hepatic SR-BI protein expression, and completely reversed by CETP expression. We conclude that chronic PXR agonism dose-dependently reduces plasma HDL-cholesterol in the presence of CETP. 相似文献
30.
Dani?l B. van Schalkwijk Albert A. de Graaf Ben van Ommen Kees van Bochove Patrick C. N. Rensen Louis M. Havekes Niek C. A. van de Pas Huub C. J. Hoefsloot Jan van der Greef Andreas P. Freidig 《Journal of lipid research》2009,50(12):2398-2411
Increased plasma cholesterol is a known risk factor for cardiovascular disease. Lipoprotein particles transport both cholesterol and triglycerides through the blood. It is thought that the size distribution of these particles codetermines cardiovascular disease risk. New types of measurements can determine the concentration of many lipoprotein size-classes but exactly how each small class relates to disease risk is difficult to clear up. Because relating physiological process status to disease risk seems promising, we propose investigating how lipoprotein production, lipolysis, and uptake processes depend on particle size. To do this, we introduced a novel model framework (Particle Profiler) and evaluated its feasibility. The framework was tested using existing stable isotope flux data. The model framework implementation we present here reproduced the flux data and derived lipoprotein size pattern changes that corresponded to measured changes. It also sensitively indicated changes in lipoprotein metabolism between patient groups that are biologically plausible. Finally, the model was able to reproduce the cholesterol and triglyceride phenotype of known genetic diseases like familial hypercholesterolemia and familial hyperchylomicronemia. In the future, Particle Profiler can be applied for analyzing detailed lipoprotein size profile data and deriving rates of various lipolysis and uptake processes if an independent production estimate is given. 相似文献