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61.
Rosiglitazone stimulates nitric oxide synthesis in human aortic endothelial cells via AMP-activated protein kinase 总被引:1,自引:0,他引:1
Boyle JG Logan PJ Ewart MA Reihill JA Ritchie SA Connell JM Cleland SJ Salt IP 《The Journal of biological chemistry》2008,283(17):11210-11217
The thiazolidinedione anti-diabetic drugs increase activation of endothelial nitric-oxide (NO) synthase by phosphorylation at Ser-1177 and increase NO bioavailability, yet the molecular mechanisms that underlie this remain poorly characterized. Several protein kinases, including AMP-activated protein kinase, have been demonstrated to phosphorylate endothelial NO synthase at Ser-1177. In the current study we determined the role of AMP-activated protein kinase in rosiglitazone-stimulated NO synthesis. Stimulation of human aortic endothelial cells with rosiglitazone resulted in the time- and dose-dependent stimulation of AMP-activated protein kinase activity and NO production with concomitant phosphorylation of endothelial NO synthase at Ser-1177. Rosiglitazone stimulated an increase in the ADP/ATP ratio in endothelial cells, and LKB1 was essential for rosiglitazone-stimulated AMPK activity in HeLa cells. Infection of endothelial cells with a virus encoding a dominant negative AMP-activated protein kinase mutant abrogated rosiglitazone-stimulated Ser-1177 phosphorylation and NO production. Furthermore, the stimulation of AMP-activated protein kinase and NO synthesis by rosiglitazone was unaffected by the peroxisome proliferator-activated receptor-gamma inhibitor GW9662. These studies demonstrate that rosiglitazone is able to acutely stimulate NO synthesis in cultured endothelial cells by an AMP-activated protein kinase-dependent mechanism, likely to be mediated by LKB1. 相似文献
62.
Invasion in space and time: non-native species richness and relative abundance respond to interannual variation in productivity and diversity 总被引:4,自引:0,他引:4
Elsa E. Cleland Melinda D. Smith Sandy J. Andelman Christy Bowles Karen M. Carney M. Claire Horner-Devine John M. Drake Sarah M. Emery Joel M. Gramling David B. Vandermast 《Ecology letters》2004,7(10):947-957
Ecologists have long sought to understand the relationships among species diversity, community productivity and invasion by non‐native species. Here, four long‐term observational datasets were analyzed using repeated measures statistics to determine how plant species richness and community resource capture (i.e. productivity) influenced invasion. Multiple factors influenced the results, including the metric used to quantify invasion, interannual variation and spatial scale. Native richness was positively correlated with non‐native richness, but was usually negatively correlated with non‐native abundance, and these patterns were stronger at the larger spatial scale. Logistic regressions indicated that the probability of invasion was reduced both within and following years with high productivity, except at the desert grassland site where high productivity was associated with increased invasion. Our analysis suggests that while non‐natives were most likely to establish in species rich communities, their success was diminished by high resource capture by the resident community. 相似文献
63.
Orotidine 5'-monophosphate decarboxylase has been heavily examined in recent years due to its enzymatic proficiency, which provides a catalytic enhancement to a reaction rate approximately 1017 times greater than that of the nonenzymatic reaction. Several mechanisms proposed to explain this catalytic enhancement have included covalent addition, ylide or carbene formation, and most recently concerted protonation. All of these mechanisms have circumvented the formation of a high-energy vinyl anionic intermediate. To investigate the presence of an anionic intermediate, 13C isotope effect studies have been performed using the alternate substrate 5-fluoro-OMP (OMP = orotidine 5'-monophosphate). Isotope effects obtained for the wild-type enzyme with OMP and 5-fluoro-OMP are 1.0255 and 1.0106, respectively, corresponding to a decrease of approximately 1.5% for 5-fluoro-OMP. With the K59A enzyme, the intrinisic isotope effects show a similar decrease of approximately 1.9% from 1.0543 with OMP to 1.0356 with 5-fluoro-OMP. This decrease results from the inductive effect of the fluorine, which stabilizes the carbanion intermediate by electron withdrawal and produces a reaction with an earlier transition state. The isotope effect for the decarboxylation of the slow substrate 2'-deoxy-OMP produced a intrinsic isotope effect of nearly 1.0461. 相似文献
64.
A kinetic investigation of the hydrolysis of semicarbazide by urease gives a relatively flat log V/ K versus pH plot between pH 5 and 8. A log V m versus pH plot shows a shift of the optimum V m toward lower pH when compared to urea. These results are explained in terms of the binding of the outer N of the NHNH 2 group in semicarbazide to an active site residue with a relatively low p K a ( approximately 6). Heavy-atom isotope effects for both leaving groups have been determined. For the NHNH 2 side, (15) k obs = 1.0045, whereas for the NH 2 side, (15) k obs = 1.0010. This is evidence that the NHNH 2 group leaves prior to the NH 2 group. Using previously published data from the urease-catalyzed hydrolysis of formamide, the commitment factors for semicarbazide and urea hydrolysis are estimated to be 2.7 and 1.2, respectively. The carbonyl-C isotope effect ( (13) k obs) equals 1.0357, which is consistent with the transition state occurring during either formation or breakdown of the tetrahedral intermediate. 相似文献
65.
D C Speckhard W B Knight J Rawlings W W Cleland 《Journal of inorganic biochemistry》1989,36(2):99-106
Cobalt(III)H2O(NH3)3 pyrophosphate has been shown by proton and 31P nuclear magnetic resonance (NMR) to be a facial bidentate complex. Cobalt(III)H2O(NH3)3 adenosine diphosphate has been resolved into lambda and delta isomers by chromatography on cycloheptaamylose. Both the lambda and delta forms are a pair of isomers that are not separated by cycloheptaamylose, reverse phase high-pressure liquid chromatography (HPLC), or cation exchange chromatography. These isomers presumably represent syn- and anti-arrangement of coordinated water and adenosine. 相似文献
66.
Ralph E. Cleland 《Molecular & general genetics : MGG》1960,91(3):303-311
Summary Seed obtained from two or three individuals in an extensiveHeterophylla population produced plants with a total of six S-factors. The number of different S-factors in the population as a whole is probably very large, and this increases very greatly the likelihood of successful pollinations among the individuals of this self-incompatible race.Dedicated to Professor Dr.Fr. Oehlkers on the occasion of his 70th birthday with respect and best wishes.Supported by the Rockefeller Foundation. 相似文献
67.
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69.
Thong Huy Cao Donald J. L. Jones Paulene A. Quinn Daniel Chu Siong Chan Narayan Hafid Helen M. Parry Mohapradeep Mohan Jatinderpal K. Sandhu Stefan D. Anker John G. Cleland Kenneth Dickstein Gerasimos Filippatos Hans L. Hillege Marco Metra Piotr Ponikowski Nilesh J. Samani Dirk J. Van Veldhuisen Faiez Zannad Aeilko H. Zwinderman Adriaan A. Voors Chim C. Lang Leong L. Ng 《Clinical proteomics》2018,15(1):35
Background
Current risk prediction models in heart failure (HF) including clinical characteristics and biomarkers only have moderate predictive value. The aim of this study was to use matrix assisted laser desorption ionisation mass spectrometry (MALDI-MS) profiling to determine if a combination of peptides identified with MALDI-MS will better predict clinical outcomes of patients with HF.Methods
A cohort of 100 patients with HF were recruited in the biomarker discovery phase (50 patients who died or had a HF hospital admission vs. 50 patients who did not have an event). The peptide extraction from plasma samples was performed using reversed phase C18. Then samples were analysed using MALDI-MS. A multiple peptide biomarker model was discovered that was able to predict clinical outcomes for patients with HF. Finally, this model was validated in an independent cohort with 100 patients with HF.Results
After normalisation and alignment of all the processed spectra, a total of 11,389 peptides (m/z) were detected using MALDI-MS. A multiple biomarker model was developed from 14 plasma peptides that was able to predict clinical outcomes in HF patients with an area under the receiver operating characteristic curve (AUC) of 1.000 (p?=?0.0005). This model was validated in an independent cohort with 100 HF patients that yielded an AUC of 0.817 (p?=?0.0005) in the biomarker validation phase. Addition of this model to the BIOSTAT risk prediction model increased the predictive probability for clinical outcomes of HF from an AUC value of 0.643 to an AUC of 0.823 (p?=?0.0021). Moreover, using the prediction model of fourteen peptides and the composite model of the multiple biomarker of fourteen peptides with the BIOSTAT risk prediction model achieved a better predictive probability of time-to-event in prediction of clinical events in patients with HF (p?=?0.0005).Conclusions
The results obtained in this study suggest that a cluster of plasma peptides using MALDI-MS can reliably predict clinical outcomes in HF that may help enable precision medicine in HF.70.
Spatial heterogeneity in species composition constrains plant community responses to herbivory and fertilisation
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Dorothee Hodapp Elizabeth T. Borer W. Stanley Harpole Eric M. Lind Eric W. Seabloom Peter B. Adler Juan Alberti Carlos A. Arnillas Jonathan D. Bakker Lori Biederman Marc Cadotte Elsa E. Cleland Scott Collins Philip A. Fay Jennifer Firn Nicole Hagenah Yann Hautier Oscar Iribarne Johannes M. H. Knops Rebecca L. McCulley Andrew MacDougall Joslin L. Moore John W. Morgan Brent Mortensen Kimberly J. La Pierre Anita C. Risch Martin Schütz Pablo Peri Carly J. Stevens Justin Wright Helmut Hillebrand 《Ecology letters》2018,21(9):1364-1371
Environmental change can result in substantial shifts in community composition. The associated immigration and extinction events are likely constrained by the spatial distribution of species. Still, studies on environmental change typically quantify biotic responses at single spatial (time series within a single plot) or temporal (spatial beta diversity at single time points) scales, ignoring their potential interdependence. Here, we use data from a global network of grassland experiments to determine how turnover responses to two major forms of environmental change – fertilisation and herbivore loss – are affected by species pool size and spatial compositional heterogeneity. Fertilisation led to higher rates of local extinction, whereas turnover in herbivore exclusion plots was driven by species replacement. Overall, sites with more spatially heterogeneous composition showed significantly higher rates of annual turnover, independent of species pool size and treatment. Taking into account spatial biodiversity aspects will therefore improve our understanding of consequences of global and anthropogenic change on community dynamics. 相似文献