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31.
Ligia Guerrero Julián Castillo Mar Qui?ones Santiago Garcia-Vallvé Lluis Arola Gerard Pujadas Bego?a Muguerza 《PloS one》2012,7(11)
Previous studies have demonstrated that certain flavonoids can have an inhibitory effect on angiotensin-converting enzyme (ACE) activity, which plays a key role in the regulation of arterial blood pressure. In the present study, 17 flavonoids belonging to five structural subtypes were evaluated in vitro for their ability to inhibit ACE in order to establish the structural basis of their bioactivity. The ACE inhibitory (ACEI) activity of these 17 flavonoids was determined by fluorimetric method at two concentrations (500 µM and 100 µM). Their inhibitory potencies ranged from 17 to 95% at 500 µM and from 0 to 57% at 100 µM. In both cases, the highest ACEI activity was obtained for luteolin. Following the determination of ACEI activity, the flavonoids with higher ACEI activity (i.e., ACEI >60% at 500 µM) were selected for further IC50 determination. The IC50 values for luteolin, quercetin, rutin, kaempferol, rhoifolin and apigenin K were 23, 43, 64, 178, 183 and 196 µM, respectively. Our results suggest that flavonoids are an excellent source of functional antihypertensive products. Furthermore, our structure-activity relationship studies show that the combination of sub-structures on the flavonoid skeleton that increase ACEI activity is made up of the following elements: (a) the catechol group in the B-ring, (b) the double bond between C2 and C3 at the C-ring, and (c) the cetone group in C4 at the C-ring. Protein-ligand docking studies are used to understand the molecular basis for these results. 相似文献
32.
Alioua A Lu R Kumar Y Eghbali M Kundu P Toro L Stefani E 《The Journal of biological chemistry》2008,283(8):4808-4817
The large conductance, voltage- and Ca2+-activated potassium (MaxiK, BK) channel and caveolin-1 play important roles in regulating vascular contractility. Here, we hypothesized that the MaxiK alpha-subunit (Slo1) and caveolin-1 may interact with each other. Slo1 and caveolin-1 physiological association in native vascular tissue is strongly supported by (i) detergent-free purification of caveolin-1-rich domains demonstrating a pool of aortic Slo1 co-migrating with caveolin-1 to light density sucrose fractions, (ii) reverse co-immunoprecipitation, and (iii) double immunolabeling of freshly isolated myocytes revealing caveolin-1 and Slo1 proximity at the plasmalemma. In HEK293T cells, Slo1-caveolin-1 association was unaffected by the smooth muscle MaxiK beta1-subunit. Sequence analysis revealed two potential caveolin-binding motifs along the Slo1 C terminus, one equivalent, 1007YNMLCFGIY1015, and another mirror image, 537YTEYLSSAF545, to the consensus sequence, varphiXXXXvarphiXXvarphi. Deletion of 1007YNMLCFGIY1015 caused approximately 80% loss of Slo1-caveolin-1 association while preserving channel normal folding and overall Slo1 and caveolin-1 intracellular distribution patterns. 537YTEYLSSAF545 deletion had an insignificant dissociative effect. Interestingly, caveolin-1 coexpression reduced Slo1 surface and functional expression near 70% without affecting channel voltage sensitivity, and deletion of 1007YNMLCFGIY1015 motif obliterated channel surface expression. The results suggest 1007YNMLCFGIY1015 possible participation in Slo1 plasmalemmal targeting and demonstrate its role as a main mechanism for caveolin-1 association with Slo1 potentially serving a dual role: (i) maintaining channels in intracellular compartments downsizing their surface expression and/or (ii) serving as anchor of plasma membrane resident channels to caveolin-1-rich membranes. Because the caveolin-1 scaffolding domain is juxtamembrane, it is tempting to suggest that Slo1-caveolin-1 interaction facilitates the tethering of the Slo1 C-terminal end to the membrane. 相似文献
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Ligia Noronha 《EcoHealth》2004,1(2):SU16
This article briefly discusses the evolution of ecosystem approaches, and illustrates the use of ecosystem approaches to assess human health and well-being in a mining context. It discusses the various elements that help distinguish such approaches from other approaches. Well-being here is understood broadly in terms of its “constituents” and “determinants,” of which health is an important constituent. Ecological, health, and social assessments highlighted a number of impacts from mining activity in Goa, India. These generated a list of issues of concern that were validated by stakeholders—community, industry, and government—which served as a basis for the development of tools to track mining-induced changes in health and well-being. The article concludes by reflecting on some of the challenges posed by the use of ecosystem approaches to assessing human health and well-being. 相似文献
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35.
Correlation between Charge Movement and Ionic Current during Slow Inactivation in Shaker K+ Channels
Riccardo Olcese Ramón Latorre Ligia Toro Francisco Bezanilla Enrico Stefani 《The Journal of general physiology》1997,110(5):579-589
Prolonged depolarization induces a slow inactivation process in some K+ channels. We have studied ionic and gating currents during long depolarizations in the mutant Shaker H4-Δ(6–46) K+ channel and in the nonconducting mutant (Shaker H4-Δ(6–46)-W434F). These channels lack the amino terminus that confers the fast (N-type) inactivation (Hoshi, T., W.N. Zagotta, and R.W. Aldrich. 1991. Neuron. 7:547–556). Channels were expressed in oocytes and currents were measured with the cut-open-oocyte and patch-clamp techniques. In both clones, the curves describing the voltage dependence of the charge movement were shifted toward more negative potentials when the holding potential was maintained at depolarized potentials. The evidences that this new voltage dependence of the charge movement in the depolarized condition is associated with the process of slow inactivation are the following: (a) the installation of both the slow inactivation of the ionic current and the inactivation of the charge in response to a sustained 1-min depolarization to 0 mV followed the same time course; and (b) the recovery from inactivation of both ionic and gating currents (induced by repolarizations to −90 mV after a 1-min inactivating pulse at 0 mV) also followed a similar time course. Although prolonged depolarizations induce inactivation of the majority of the channels, a small fraction remains non–slow inactivated. The voltage dependence of this fraction of channels remained unaltered, suggesting that their activation pathway was unmodified by prolonged depolarization. The data could be fitted to a sequential model for Shaker K+ channels (Bezanilla, F., E. Perozo, and E. Stefani. 1994. Biophys. J. 66:1011–1021), with the addition of a series of parallel nonconducting (inactivated) states that become populated during prolonged depolarization. The data suggest that prolonged depolarization modifies the conformation of the voltage sensor and that this change can be associated with the process of slow inactivation. 相似文献
36.
The abundance of calcareous green algae was recorded quarterly at 28 sites within the Florida Keys National Marine Sanctuary (FKNMS) for a period of 7 years as part of a sea grass monitoring program. To evaluate the validity of using the functional‐form group approach, we designed a sampling method that included the functional‐form group and the component genera. This strategy enabled us to analyze the spatiotemporal patterns in the abundance of calcareous green algae as a group and to describe synchronous behavior among its genera through the application of a nonlinear regression model to both categories of data. Spatial analyses revealed that, in general, all genera displayed long‐term trends of increasing abundance at most sites; however, at some sites the long‐term trends for genera opposed one another. Strong synchrony in the timing of seasonal changes was found among all genera, possibly reflecting similar reproductive and seasonal growth pattern, but the variability in the magnitude of seasonal changes was very high among genera and sites. No spatial patterns were found in long‐term or seasonal changes; the only significant relation detected was for slope, with sites closer to land showing higher values, suggesting that some factors associated with land proximity are affecting this increase. We conclude that the abundances of genera behaved differently from the functional‐form group, indicating that the use of the functional‐form group approach may be unsuitable to detect changes in sea grass community structure in the FKNMS at the existing temporal and spatial scale of the monitoring program. 相似文献
37.
The D2 and D3 dopamine receptor subtypes are structurally homologous and couple to the same signal transduction pathways. Nevertheless, their evolutionary conservation suggests that the two subtypes might exhibit unique signaling characteristics. We previously determined that D3 but not D2S dopamine receptor exhibits a tolerance property in which the D3 receptor-activated G-protein coupled inward rectifier potassium currents progressively decreases upon repeated agonist stimulation. In this paper, using AtT-20 neuroendocrine cells stably expressing either human D3 or D2S receptor, we show that the tolerance property is also observed in the D3 receptor-adenylyl cyclase and D3 receptor-mitogen-activated protein kinase signaling pathways. We have previously shown that the second cytoplasmic loop of D3 receptor is required for tolerance. Here, using site-directed mutagenesis, we identified the specific amino acids in the D3 second cytoplasmic loop involved in the tolerance property. The results show that substitution of a non-conserved cysteine residue at position 147 with positively-charged lysine or arginine residues abolishes tolerance. Interestingly, the cysteine 147 residue is embedded in a putative phosphorylation site adjacent to two serine residues. Mutation of these serine residues to alanine also attenuates tolerance. Taken together, these structural studies suggest a role for phosphorylation in D3 receptor tolerance property. 相似文献
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The spider tree of life: phylogeny of Araneae based on target‐gene analyses from an extensive taxon sampling
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Ward C. Wheeler Jonathan A. Coddington Louise M. Crowley Dimitar Dimitrov Pablo A. Goloboff Charles E. Griswold Gustavo Hormiga Lorenzo Prendini Martín J. Ramírez Petra Sierwald Lina Almeida‐Silva Fernando Alvarez‐Padilla Miquel A. Arnedo Ligia R. Benavides Silva Suresh P. Benjamin Jason E. Bond Cristian J. Grismado Emile Hasan Marshal Hedin Matías A. Izquierdo Facundo M. Labarque Joel Ledford Lara Lopardo Wayne P. Maddison Jeremy A. Miller Luis N. Piacentini Norman I. Platnick Daniele Polotow Diana Silva‐Dávila Nikolaj Scharff Tamás Szűts Darrell Ubick Cor J. Vink Hannah M. Wood Junxia Zhang 《Cladistics : the international journal of the Willi Hennig Society》2017,33(6):574-616