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321.
Victor N. Uebele Cindy E. Nuss Steven V. Fox Susan L. Garson Razvan Cristescu Scott M. Doran Richard L. Kraus Vincent P. Santarelli Yuxing Li James C. Barrow Zhi-Qiang Yang Kelly-Ann S. Schlegel Kenneth E. Rittle Thomas S. Reger Rodney A. Bednar Wei Lemaire Faith A. Mullen Jeanine E. Ballard Cuyue Tang Ge Dai Owen B. McManus Kenneth S. Koblan John J. Renger 《Cell biochemistry and biophysics》2009,55(2):81-93
Low-voltage-activated (T-type) calcium channels play a role in diverse physiological responses including neuronal burst firing, hormone secretion, and cell growth. To better understand the biological role and therapeutic potential of the target, a number of structurally diverse antagonists have been identified. Multiple drug interaction sites have been identified for L-type calcium channels, suggesting a similar possibility exists for the structurally related T-type channels. Here, we radiolabel a novel amide T-type calcium channel antagonist (TTA-A1) and show that several known antagonists, including mibefradil, flunarizine, and pimozide, displace binding in a concentration-dependent manner. Further, we identify a novel quinazolinone T-type antagonist (TTA-Q4) that enhanced amide radioligand binding, increased affinity in a saturable manner and slowed dissociation. Functional evaluation showed these compounds to be state-dependent antagonists which show a positive allosteric interaction. Consistent with slowing dissociation, the duration of efficacy was prolonged when compounds were co-administered to WAG/Rij rats, a genetic model of absence epilepsy. The development of a T-type calcium channel radioligand has been used to demonstrate structurally distinct TTAs interact at allosteric sites and to confirm the potential for synergistic inhibition of T-type calcium channels with structurally diverse antagonists. 相似文献
322.
Tryon CA Tyler Faith J Peppe DJ Fox DL McNulty KP Jenkins K Dunsworth H Harcourt-Smith W 《Journal of human evolution》2010,59(6):657-671
Western Kenya is well known for abundant early Miocene hominoid fossils. However, the Wasiriya Beds of Rusinga Island, Kenya, preserve a Pleistocene sedimentary archive with radiocarbon age estimates of >33–45 ka that contains Middle Stone Age artifacts and abundant, well-preserved fossil fauna: a co-occurrence rare in eastern Africa, particularly in the region bounding Lake Victoria. Artifacts and fossils are associated with distal volcanic ash deposits that occur at multiple localities in the Wasiriya Beds, correlated on the basis of geochemical composition as determined by electron probe microanalysis. Sediment lithology and the fossil ungulates suggest a local fluvial system and associated riparian wooded habitat within a predominantly arid grassland setting that differs substantially from the modern environment, where local climate is strongly affected by moisture availability from Lake Victoria. In particular, the presence of oryx (Oryx gazella) and Grevy’s zebra (Equus grevyi) suggest a pre-Last Glacial Maximum expansion of arid grasslands, an environmental reconstruction further supported by the presence of several extinct specialized grazers (Pelorovis antiquus, Megalotragus sp., and a small alcelaphine) that are unknown from Holocene deposits in eastern Africa. The combination of artifacts, a rich fossil fauna, and volcaniclastic sediments makes the Wasiriya Beds a key site for examining the Lake Victoria basin, a biogeographically important area for understanding the diversification and dispersal of Homo sapiens from Africa, whose pre-Last Glacial Maximum history remains poorly understood. 相似文献
323.
Lower termites rely on cellulolytic protozoa to aid in the digestion of their wood-based diet. However, despite the major contribution of protozoa to the lower termite digestive system, few techniques have been developed to monitor shifts in protozoan populations. This study investigated whether quantitative real-time PCR (qRT-PCR) and/or cellulase enzyme assays can be used to monitor changes of cellulolytic protozoan populations in the lower termite, Reticulitermes flavipes (Kollar). Previously developed cellulase primer sets were used to test for changes in cellulase gene expression, while three different cellulase enzyme assays were used to assess changes in cellulase enzyme activity. The results from this study indicate that qRT-PCR is a reliable method to monitor shifts in cellulolytic protozoan populations. Specifically, qRT-PCR can serve as a useful monitoring technique during high-throughput screening of novel termite control agents such as cellulase inhibitors, and help to answer questions relating to whether or not such control agents impact cellulolytic protozoan populations. 相似文献
324.
Laurdan is a fluorescent probe that detects changes in membrane phase properties through its sensitivity to the polarity of its environment in the bilayer. Variations in membrane water content cause shifts in the laurdan emission spectrum, which are quantified by calculating the generalized polarization (GP). We tested whether laurdan fluorescence could be used to distinguish differences in phospholipid order from changes in membrane fluidity by examining the temperature dependence of laurdan GP and fluorescence anisotropy in dipalmitoylphosphatidylcholine (DPPC) vesicles. The phase transition from the solid ordered phase to the liquid disordered phase was observed as a decrease in laurdan GP values from 0.7 to −0.14 and a reduction in anisotropy from 0.25 to 0.12. Inclusion of various amounts of cholesterol in the membranes to generate a liquid ordered phase caused an increase in the apparent melting temperature detected by laurdan GP. In contrast, cholesterol decreased the apparent melting temperature estimated from anisotropy measurements. Based on these results, it appeared that laurdan anisotropy detected changes in membrane fluidity while laurdan GP sensed changes in phospholipid order. Thus, the same fluorescent probe can be used to distinguish effects of perturbations on membrane order and fluidity by comparing the results of fluorescence emission and anisotropy measurements. 相似文献
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326.
Jeremiah J Faith Andrew J Olson Timothy S Gardner Ravi Sachidanandam 《BMC bioinformatics》2007,8(1):344
Background
Lightweight genome viewer (lwgv) is a web-based tool for visualization of sequence annotations in their chromosomal context. It performs most of the functions of larger genome browsers, while relying on standard flat-file formats and bypassing the database needs of most visualization tools. Visualization as an aide to discovery requires display of novel data in conjunction with static annotations in their chromosomal context. With database-based systems, displaying dynamic results requires temporary tables that need to be tracked for removal. 相似文献327.
328.
Greg Clark Cameron Darwin Viraj Mehta Faith Jackobs Tyler Perry Katia Hougaard Stan Roux 《Plant signaling & behavior》2013,8(11)
In Arabidopsis leaves there is a bi-phasic dose-response to applied nucleotides; i.e., lower concentrations induce stomatal opening, while higher concentrations induce closure. Two mammalian purinoceptor antagonists, PPADS and RB2, block both nucleotide-induced stomatal opening and closing. These antagonists also partially block ABA-induced stomatal closure and light-induced stomatal opening. There are two closely related Arabidopsis apyrases, AtAPY1 and AtAPY2, which are both expressed in guard cells. Here we report that low levels of apyrase chemical inhibitors can induce stomatal opening in the dark, while apyrase enzyme blocks ABA-induced stomatal closure. We also demonstrate that high concentrations of ATP induce stomatal closure in the light. Application of ATPγS and chemical apyrase inhibitors at concentrations that have no effect on stomatal closure can lower the threshold for ABA-induced closure. The closure induced by ATPγS was not observed in gpa1-3 loss-of-function mutants. These results further confirm the role of extracellular ATP in regulating stomatal apertures. 相似文献
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330.