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Short treatment (up to 1 h) of cytosine arabinoside (araC) increases the frequencies of aberrations induced by X-rays in human lymphocytes, evaluated at the first mitosis following stimulation, or as prematurely condensed chromosomes of G0 nuclei. Parallel biochemical experiments using nucleoid sedimentation technique, demonstrate that araC inhibits rejoining of DNA-strand breaks effectively. These results point out that X-ray-induced short-lived DNA strand breaks lead to chromosomal aberrations in human lymphocytes. 相似文献
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van den Brink F. S. Meijers T. A. Hofma S. H. van Boven A. J. Nap A. Vonk A. Symersky P. Sjauw K. D. Knaapen P. 《Netherlands heart journal》2020,28(3):139-144
Netherlands Heart Journal - Complex high-risk percutaneous coronary intervention (PCI) is challenging and frequently accompanied by haemodynamic instability. Veno-arterial extracorporeal membrane... 相似文献
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Ants are powerful model systems for the study of cooperation and sociality. In this review, we discuss how recent advances in ant genomics have contributed to our understanding of the evolution and organization of insect societies at the molecular level. 相似文献
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W. C. Meijers T. Hoekstra T. Jaarsma D. J. van Veldhuisen R. A. de Boer 《Netherlands heart journal》2016,24(4):287-295
Aims
Heart failure with preserved ejection fraction (HFpEF) is common and its management remains difficult. B-type natriuretic peptide (BNP) levels are used to diagnose heart failure, and as an entry criterion for inclusion into trials. We investigated a population of HFpEF patients who had been randomised into a study based on clinical parameters, and compared those with low BNP levels to those with elevated BNP levels.Methods
We examined patients who had been enrolled in the Coordinating study evaluating Outcomes of Advising and Counselling in Heart Failure (COACH), with preserved left ventricular ejection fraction (LVEF ≥ 40 %), and compared those with low BNP (< 100 pg/ml; n = 30) to those with elevated BNP (≥ 100 pg/ml; n = 127). Baseline characteristics, comorbidities, biomarkers, quality of life, and outcome parameters (hospitalisations and death) were compared between the groups. To validate our findings, we repeated all analyses for NT-proBNP (< 300 pg/ml and ≥ 300 pg/ml).Results
Patients were similar with regard to most clinical characteristics (including age, sex, and LVEF), biomarkers, and comorbidities. In contrast, patients with a low BNP had higher body mass index levels (31 kg/m2 vs. 27 kg/m2; p < 0.01) and lower cardiac troponin I (9 pg/ml vs. 15 pg/ml; p = 0.02). In addition, these patients were less frequently prescribed diuretics and beta-blockers. No differences in quality of life, heart failure related symptoms and the primary and secondary outcomes were observed between these groups. These observations were confirmed for NT-proBNP.Conclusion
Among the patients with clinically diagnosed HFpEF, those with low BNP are strikingly similar to those with elevated BNP levels, except for BMI, which was significantly higher in these patients.Electronic supplementary material
The online version of this article (doi:10.1007/s12471-016-0816-8) contains supplementary material, which is available to authorized users. 相似文献16.
Attenuation of pattern recognition receptor signaling is mediated by a MAP kinase kinase kinase
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Sharon C Mithoe Christina Ludwig Michiel JC Pel Mara Cucinotta Alberto Casartelli Malick Mbengue Jan Sklenar Paul Derbyshire Silke Robatzek Corné MJ Pieterse Ruedi Aebersold Frank LH Menke 《EMBO reports》2016,17(3):441-454
Pattern recognition receptors (PRRs) play a key role in plant and animal innate immunity. PRR binding of their cognate ligand triggers a signaling network and activates an immune response. Activation of PRR signaling must be controlled prior to ligand binding to prevent spurious signaling and immune activation. Flagellin perception in Arabidopsis through FLAGELLIN‐SENSITIVE 2 (FLS2) induces the activation of mitogen‐activated protein kinases (MAPKs) and immunity. However, the precise molecular mechanism that connects activated FLS2 to downstream MAPK cascades remains unknown. Here, we report the identification of a differentially phosphorylated MAP kinase kinase kinase that also interacts with FLS2. Using targeted proteomics and functional analysis, we show that MKKK7 negatively regulates flagellin‐triggered signaling and basal immunity and this requires phosphorylation of MKKK7 on specific serine residues. MKKK7 attenuates MPK6 activity and defense gene expression. Moreover, MKKK7 suppresses the reactive oxygen species burst downstream of FLS2, suggesting that MKKK7‐mediated attenuation of FLS2 signaling occurs through direct modulation of the FLS2 complex. 相似文献
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Marx PF Hackeng TM Dawson PE Griffin JH Meijers JC Bouma BN 《The Journal of biological chemistry》2000,275(17):12410-12415
Thrombin-activable fibrinolysis inhibitor (TAFI) is present in the circulation as an inactive zymogen. Thrombin converts TAFI to a carboxypeptidase B-like enzyme (TAFIa) by cleaving at Arg(92) in a process accelerated by the cofactor, thrombomodulin. TAFIa attenuates fibrinolysis. TAFIa can be inactivated by both proteolysis by thrombin and spontaneous temperature-dependent loss of activity. The identity of the thrombin cleavage site responsible for loss of TAFIa activity was suggested to be Arg(330), but site-directed mutagenesis of this residue did not prevent inactivation of TAFIa by thrombin. In this study we followed TAFI activation and TAFIa inactivation by thrombin/thrombomodulin in time and characterized the cleavage pattern of TAFI using matrix-assisted laser desorption ionization mass spectrometry. Mass matching of the fragments revealed that TAFIa was cleaved at Arg(302). Studies of a mutant R302Q-TAFI confirmed identification of this thrombin cleavage site and, furthermore, suggested that inactivation of TAFIa is based on its conformational instability rather than proteolytic cleavage at Arg(302). 相似文献
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Ling?HuangEmail author Anton?W.?Langerak Ingrid?L.?M.?Wolvers-Tettero Ruud?W.?J.?Meijers Carla?C.?Baan Nicolle?H.?R.?Litjens Michiel?G.?H.?Betjes 《Immunity & ageing : I & A》2015,12(1):28