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91.
Meltzer RH Vila-Carriles W Ebalunode JO Briggs JM Pedersen SE 《Biophysical journal》2006,91(4):1325-1335
Electrostatic surface potentials in the vestibule of the nicotinic acetylcholine receptor (nAChR) were computed from structural models using the University of Houston Brownian Dynamics program to determine their effect on ion conduction and ionic selectivity. To further determine whether computed potentials accurately reflect the electrostatic environment of the channel, the potentials were used to predict the rate constants for diffusion-enhanced fluorescence energy transfer; the calculated energy transfer rates are directly comparable with those determined experimentally (see companion article by Meltzer et al. in this issue). To include any effects on the local potentials by the bound acceptor fluorophore crystal violet, its binding site was first localized within the pore by fluorescence energy transfer measurements from dansyl-C6-choline bound to the agonist sites and also by simulations of binding using Autodock. To compare the computed potentials with those determined experimentally, we used the predicted energy transfer rates from Tb3+ chelates of varying charge to calculate an expected potential using the Boltzmann relationship. This expected potential (from -20 to -40 mV) overestimates the values determined experimentally (from -10 to -25 mV) by two- to fourfold at similar conditions of ionic strength. Although the results indicate a basic discrepancy between experimental and computed surface potentials, both methods demonstrate that the vestibular potential has a relatively small effect on conduction and selectivity. 相似文献
92.
O'Shea PJ Kim DW Logan JG Davis S Walker RL Meltzer PS Cheng SY Williams GR 《The Journal of biological chemistry》2012,287(21):17812-17822
Thyroid hormone (T(3)) acts in chondrocytes and bone-forming osteoblasts to control bone development and maintenance, but the signaling pathways mediating these effects are poorly understood. Thrb(PV/PV) mice have a severely impaired pituitary-thyroid axis and elevated thyroid hormone levels due to a dominant-negative mutant T(3) receptor (TRβ(PV)) that cannot bind T(3) and interferes with the actions of wild-type TR. Thrb(PV/PV) mice have accelerated skeletal development due to unknown mechanisms. We performed microarray studies in primary osteoblasts from wild-type mice and Thrb(PV/PV) mice. Activation of the canonical Wnt signaling in Thrb(PV/PV) mice was confirmed by in situ hybridization analysis of Wnt target gene expression in bone during postnatal growth. By contrast, T(3) treatment inhibited Wnt signaling in osteoblastic cells, suggesting that T(3) inhibits the Wnt pathway by facilitating proteasomal degradation of β-catenin and preventing its accumulation in the nucleus. Activation of the Wnt pathway in Thrb(PV/PV) mice, however, results from a gain of function for TRβ(PV) that stabilizes β-catenin despite the presence of increased thyroid hormone levels. These studies demonstrate novel interactions between T(3) and Wnt signaling pathways in the regulation of skeletal development and bone formation. 相似文献
93.
94.
The shrimp fishery is the most economically important fishery in Mexico. The trawler-based portion of this fishery results in high rates of by-catch. This study quantifies and describes the biodiversity of by-catch associated with trawling in the Bahía de Kino region of Sonora, Mexico. Data were collected from 55 trawls, on six boats, over 14 nights, during November of 2003, 2004, 2006-2009. By-catch rates within trawl samples averaged 85.9% measured by weight. A total of 183 by-catch species were identified during the course of this study, including 97 species of bony fish from 43 families, 19 species of elasmobranchs from 12 families, 66 species of invertebrates from eight phyla, and one species of marine turtle; seven of the documented by-catch species are listed on the IUCN Red List, CITES, or the Mexican NOM-059-ECOL-2010; 35 species documented in the by-catch are also targeted by local artisanal fishers. Some of the species frequently captured as juveniles in the by-catch are economically important to small-scale fishers in the region, and are particularly sensitive to overexploitation due to their life histories. This study highlights the need for further research quantifying the impacts of high levels of by-catch upon small-scale fishing economies in the region and presents strong ecological and economic rationale for by-catch management within the shrimp fishery of the Gulf of California. Site-specific by-catch management plans should be piloted in the Bahía de Kino region to address the growing momentum in national and international fisheries policy regimes toward the reduction of by-catch in shrimp fisheries. 相似文献
95.
96.
Boyle AP Davis S Shulha HP Meltzer P Margulies EH Weng Z Furey TS Crawford GE 《Cell》2008,132(2):311-322
97.
三羟异黄酮(genistein)是大豆中的一种非营养成分,其结构与黄酮化合物类似,能竞争性地与雌激素受体结合,故称之为植物雌激素(phytoestrogen)。它具有广泛的生物学作用,如抗肿瘤、抗病毒、抗真菌、抗氧化、抗突变、抗高血压、抗增生等,其中genistein抑制肿瘤的血管生成是当前研究的热点之一。肿瘤的血管生成是肿瘤进一步生长转移的基础,该过程受肿瘤细胞和血管内皮细胞分泌的血管生成相关因 相似文献
98.
从1973年发现核小体至今,研究者们对染色质纤维结构和这种纤维组织成染色体的方式进行了广泛而深入的研究。由DNA到核小体到30nm染色质纤维几乎公认是按螺旋方式集缩的,但是有关30nm左右染色质纤维如何压缩形成染色体的高层次结构还没有统一的意见。关于这方面的研究目前已有许多模型。其中,Bak等提出的多级螺旋 相似文献
99.
100.
A. A. Imam H. S. Novey H. A. Orgel G. L. Klein E. O. Meltzer R. W. Ziering 《The Western journal of medicine》1990,152(3):313-316
The Quidel allergy screen is a relatively rapid (less than 2 hours) multiallergen dipstick method for detecting specific immunoglobin E antibodies in serum. It was developed to answer the need of primary physician nonspecialists in allergy for a convenient in-office screening test for diagnosing allergy. The new test was evaluated against the benchmark diagnostic skin tests and the radioallergosorbent serologic tests for sensitivity, specificity, accuracy, and technical feasibility in an office setting. It was found that while the Quidel allergy screen lacks the specificity of the standard tests, its overall sensitivity, as defined by the percentage of patients with positive skin reactions who also tested positive with the Quidel screen (68%), its ease of use, and its rapidity warrant its consideration as a screening tool for confirming a possible case of allergy. 相似文献