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排序方式: 共有229条查询结果,搜索用时 187 毫秒
31.
Nian Zhou Wayne Zeller Jun Zhang Emmanuel Onua Alex S. Kiselyov Jose Ramirez Guðrún Palsdottir Guðrún Halldorsdottir Þorkell Andrésson Mark E. Gurney Jasbir Singh 《Bioorganic & medicinal chemistry letters》2009,19(5):1528-1531
A series of potent and selective EP3 receptor antagonists are described. Utilizing a pharmacophore model developed for the EP3 receptor, a series of 3,4-disubstituted indoles were found to be efficient ligands for this target. These compounds showed high selectivity over IP, FP and other EP receptors. An optimized molecule 7c featured a sound profile and potency in the functional rat and human platelet aggregation assays. 相似文献
32.
We test the model of early visual processing introduced in the companion paper by simulating a range of psychophysical phenomena. We present new data concerning our ability to discriminate the speed of drifting gratings when spatiotemporally apertured in a variety of ways. We shall investigate the role played by the aperture in modifying the grating's behaviour from its idealisation as a pure Fourier component and show that this is not negligible. Other phenomena which we simulate and explain relate to the way perceived velocity is influenced by contrast and spatial frequency. Many of our explanations are couched in terms of the relative number of cells occurring within each locale of the Fourier domain. This use of the cell density map is a unifying concept and avoids the necessity for a range of separate mechanisms. We argue that a neurophysiologically detailed model is necessary in order to explain psychophysical data (Weber fractions) which vary over less than an order of magnitude, and small deviations from veridical encoding of velocity. 相似文献
33.
Janey Symington Theodore Gurney George L. Eliceiri 《Biochemical and biophysical research communications》1984,120(1):81-87
Whole nuclear and cytoplasmic fractions from HeLa cells were analyzed in protein gel blots probed with either monoclonal anti-Sm or polyclonal anti-(U1)RNP antibodies. The cells were fractionated by a nonaqueous procedure, to minimize proteolysis and artifactual leakage of nuclear components to the cytoplasmic fraction. Unexpectedly, more reactive proteins were detected in the nucleus than shown earlier in partially purified small nuclear ribonucleoprotein particles (snRNPs). In addition, reactive polypeptides were now found in the cytoplasm. These results are discussed in reference to the possibility that the nucleus and cytoplasm of adult somatic human cells may have a more complex than anticipated set of populations of polypeptides bearing Sm or RNP antigenic determinants, including some proteins that might not be in snRNP form. 相似文献
34.
35.
Ecological stability and social hierarchy 总被引:1,自引:0,他引:1
We have examined a predator-prey model in which the predator is assumed to have a social structure of the dominance hierarchy or “peck order” type in which the feeding success of an individual is related both to the availability of food and to his social rank. We find such a social structure to be a strongly beneficial influence on population stability so long as the rewards of social dominance are not too extreme. We also show that an optimally hierarchical predator population can stably achieve a much larger depression of the prey below its carrying capacity than is possible for a simple predator population composed of identical individuals. This strongly suggests that socially structured predator populations may be more effective agents of biological control than simpler predators with no such population structure. 相似文献
36.
Two-pore domain (K2P) channels emerged about a decade ago and since then have been an expanding area of interest. This is because their biophysical
and pharmacological properties make them good candidates to support background potassium currents and membrane potential in
many cell types. There is clear evidence for TREK-1 and TASK-1 in the heart and these channels are likely to regulate cardiac
action potential duration through their regulation by stretch, polyunsaturated fatty acids, pH, and neurotransmitters. TREK-1
may also have a critical role in mediating the vasodilator response of resistance arteries to polyunsaturated fatty acids,
thus contributing to their protective effect on the cardiovascular system. TASK-1, on the other hand, is a strong candidate
for a role in hypoxic vasoconstriction of pulmonary arteries. Many other members of the K2P channel family have been identified in the cardiovascular system, although their functional roles are still to be demonstrated.
This review provides an up to date summary of what is known about the involvement of members of the K2P channel family in cells of the heart and arterial circulation. Our knowledge of their roles will improve with the rapidly
increasing interest in them and as new selective pharmacological tools emerge. As their physiological roles emerge, the K2P family of potassium channels may offer promising therapeutic solutions to target cardiovascular diseases.
EBSA satellite meeting: ion channels, Leeds, July 2007. 相似文献
37.
Matthew O’Connell Wayne Zeller James Burgeson Rama K. Mishra Jose Ramirez Alex S. Kiselyov Þorkell Andrésson Mark E. Gurney Jasbir Singh 《Bioorganic & medicinal chemistry letters》2009,19(3):778-782
A series of peri-substituted [4.3.0] bicyclic non-aromatic heterocycles have been identified as potent and selective hEP3 receptor antagonists. These molecules adopt a hair-pin conformation that overlaps with the endogenous ligand PGE2 and fits into an internally generated EP3 pharmacophore model. Optimized compounds show good metabolic stability and improved solubility over their corresponding bicyclic aromatic analogs. 相似文献
38.
Previous studies have documented advancement in clutch initiation dates (CIDs) in response to climate change, most notably for temperate-breeding passerines. Despite accelerated climate change in the Arctic, few studies have examined nest phenology shifts in arctic breeding species. We investigated whether CIDs have advanced for the most abundant breeding shorebird and passerine species at a long-term monitoring site in arctic Alaska. We pooled data from three additional nearby sites to determine the explanatory power of snow melt and ecological variables (predator abundance, green-up) on changes in breeding phenology. As predicted, all species (semipalmated sandpiper, Calidris pusilla, pectoral sandpiper, Calidris melanotos, red-necked phalarope, Phalaropus lobatus, red phalarope, Phalaropus fulicarius, Lapland longspur, Calcarius lapponicus) exhibited advanced CIDs ranging from 0.40 to 0.80 days/year over 9 years. Timing of snow melt was the most important variable in explaining clutch initiation advancement (“climate/snow hypothesis”) for four of the five species, while green-up was a much less important explanatory factor. We found no evidence that high predator abundances led to earlier laying dates (“predator/re-nest hypothesis”). Our results support previous arctic studies in that climate change in the cryosphere will have a strong impact on nesting phenology although factors explaining changes in nest phenology are not necessarily uniform across the entire Arctic. Our results suggest some arctic-breeding shorebird and passerine species are altering their breeding phenology to initiate nesting earlier enabling them to, at least temporarily, avoid the negative consequences of a trophic mismatch. 相似文献
39.
40.
Photoinduced removal of nifedipine reveals mechanisms of calcium antagonist action on single heart cells 总被引:7,自引:2,他引:5
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The currents through voltage-activated calcium channels in heart cell membranes are suppressed by dihydropyridine calcium antagonists such as nifedipine. Nifedipine is photolabile, and the reduction of current amplitude by this drug can be reversed within a few milliseconds after a 1-ms light flash. The blockade by nifedipine and its removal by flashes were studied in isolated myocytes from neonatal rat heart using the whole-cell clamp method. The results suggest that nifedipine interacts with closed, open, and inactivated calcium channels. It is likely that at the normal resting potential of cardiac cells, the suppression of current amplitude arises because nifedipine binds to and stabilizes channels in the resting, closed state. Inhibition is enhanced at depolarized membrane potentials, where interaction with inactivated channels may also become important. Additional block of open channels is suggested when currents are carried by Ba2+ but is not indicated with Ca2+ currents. Numerical simulations reproduce the experimental observations with molecular dissociation constants on the order of 10(-7) M for closed and open channels and 10(-8) M for inactivated channels. 相似文献