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991.
4-Acylamino-6-arylfuro[2,3-d]pyrimidines: potent and selective glycogen synthase kinase-3 inhibitors
Maeda Y Nakano M Sato H Miyazaki Y Schweiker SL Smith JL Truesdale AT 《Bioorganic & medicinal chemistry letters》2004,14(15):3907-3911
Modeling studies of a furo[2,3-d]pyrimidine GSK-3 hit compound 1 superimposed onto the X-ray crystal structure of a legacy pyrazolo[3,4-c]pyridazine GSK-3 inhibitor 2 led to the identification of 4-acylamino-6-arylfuro[2,3-d]pyrimidine template 3. Synthesis of analogues based on template 3 has resulted in a number of potent and selective GSK-3beta inhibitors. The most potent and selective compound was the m-pyridyl analogue 24. 相似文献
992.
Aonghus?J?O'Loughlin Crochan?J?O'Sullivan Nandini?Ravikumar Anne?M?Friel John?T?Elliott John?J?MorrisonEmail author 《Reproductive biology and endocrinology : RB&E》2005,3(1):8
Background
The non-thrombotic effects of thrombin in cardiovascular tissues, as mediated via the protease activated receptors (PARs), and particularly PAR-1, have been the focus of much recent research. The aims of this study were to evaluate the effects of thrombin, a specific PAR-1 activating peptide (PAR1-AP), and a PAR-1 antagonist on human umbilical artery tone in vitro. 相似文献993.
Christian Boucher Anne Martinel Patrick Barberis Genevieve Alloing Claudine Zischek 《Molecular & general genetics : MGG》1986,205(2):270-275
Summary A class of avirulent mutants of the plant pathogenic bacterium Pseudomonas solanacearum, strain GMI1000, resistant to acridine orange (Acrr), harbour a deletion of over 85 kb in their genome. This deletion affects, a1,000 kb megaplasmid which has previously been shown to be present in most of the strains of this species. In addition at least 11 out of 13 independent Tn5 insertions, leading to loss of virulence, are located on the megaplasmid. Nine of them are present in the region which is deleted from the Acrr mutants. These results suggest that the majority of virulence genes identified so far are plasmid borne. 相似文献
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996.
The endoplasmic reticulum (ER) of most vertebrate cells is spread out by kinesin-dependent transport along microtubules, whereas studies in Saccharomyces cerevisiae indicated that motility of fungal ER is an actin-based process. However, microtubules are of minor importance for organelle transport in yeast, but they are crucial for intracellular transport within numerous other fungi. Herein, we set out to elucidate the role of the tubulin cytoskeleton in ER organization and dynamics in the fungal pathogen Ustilago maydis. An ER-resident green fluorescent protein (GFP)-fusion protein localized to a peripheral network and the nuclear envelope. Tubules and patches within the network exhibited rapid dynein-driven motion along microtubules, whereas conventional kinesin did not participate in ER motility. Cortical ER organization was independent of microtubules or F-actin, but reformation of the network after experimental disruption was mediated by microtubules and dynein. In addition, a polar gradient of motile ER-GFP stained dots was detected that accumulated around the apical Golgi apparatus. Both the gradient and the Golgi apparatus were sensitive to brefeldin A or benomyl treatment, suggesting that the gradient represents microtubule-dependent vesicle trafficking between ER and Golgi. Our results demonstrate a role of cytoplasmic dynein and microtubules in motility, but not peripheral localization of the ER in U. maydis. 相似文献
997.
Estimating the abundance of burrow‐nesting species through the statistical analysis of combined playback and visual surveys 下载免费PDF全文
Anne‐Sophie Bonnet‐Lebrun Licia Calabrese Gerard Rocamora Andrés López‐Sepulcre 《Journal of avian biology》2016,47(5):642-649
The conservation of elusive species relies on our ability to obtain unbiased estimates of their abundance trends. Many species live or breed in cavities, making it easy to define the search units (the cavity) yet hard to ascertain their occupancy. One such example is that of certain colonial seabirds like petrels and shearwaters, which occupy burrows to breed. In order to increase the chances of detection for these types of species, their sampling can be done using two independent methods to check for cavity occupancy: visual inspection, and acoustic response to a playback call. This double‐detection process allows us to estimate the probability of burrow occupancy by accounting for the probability of detection associated with each method. Here we provide a statistical framework to estimate the occupancy and population size of burrow‐dwelling species. We show how to implement the method using both maximum likelihood and Bayesian approaches, and test its precision and bias using simulated datasets. We subsequently illustrate how to extend the method to situations where two different species may occupy the burrows, and apply it to a dataset on wedge‐tailed shearwaters Puffinus pacificus and tropical shearwaters P. bailloni on Aride Island, Seychelles. The simulations showed that the single‐species model performed well in terms of error and bias except when detection probabilities and occupancies were very low. The two‐species model applied to shearwaters showed that detection probabilities were highly heterogeneous. The population sizes of wedge‐tailed and tropical shearwaters were estimated at 13 716 (95% CI: 12 909–15 874) and 25 550 (23 667–28 777) pairs respectively. The advantages of formulating the call‐playback sampling method statistically is that it provides a framework to calculate uncertainty in the estimates and model assumptions. This method is applicable to a variety of cavity‐dwelling species where two methods can be used to detect cavity occupancy. 相似文献
998.
Rayalam S Della-Fera MA Ambati S Boyan B Baile CA 《Biochemical and biophysical research communications》2007,364(3):450-456
Guggulsterone (GS) and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] have been shown to influence adipogenesis in 3T3-L1 cells. We investigated the ability of GS and 1,25(OH)2D3, alone and in combination to inhibit adipogenesis and induce apoptosis in 3T3-L1 adipocytes. Maturing preadipocytes were treated with 1,25(OH)2D3 in combination with GS for 6 days during differentiation. GS and 1,25(OH)2D3 each inhibited lipid accumulation, but the combination potentiated the inhibition of lipid accumulation. Apoptosis was increased by 1,25(OH)2D3 while GS had no effect, but GS + 1,25(OH)2D3 increased apoptosis more than either compound alone. Furthermore, GS + 1,25(OH)2D3 caused a potentiated decrease in the expression of aP2 and farnesoid X receptor expression more than either compound alone. In addition, 1,25(OH)2D3 increased vitamin D receptor expression after 6 days, while GS had no effect. GS + 1,25(OH)2D3, however, caused a potentiated increase in the expression of VDR. These findings show that GS potentiates 1,25(OH)2D3’s anti-adipogenic and pro-apoptotic effects in maturing 3T3-L1 preadipocytes. 相似文献
999.
Marie E. Herberstein Jutta M. Schneider Aaron M. T. Harmer Anne C. Gaskett Katherine Robinson Kim Shaddick Daniel Soetkamp Peter D. Wilson Stano Pekár Mark A. Elgar 《Journal of Ethology》2011,29(1):9-15
Female St Andrew’s Cross spiders control copulation duration by timing sexual cannibalism and may thereby control paternity
if cannibalism affects sperm transfer. We have investigated the effect of copulation duration on sperm transfer and documented
sperm storage patterns when we experimentally reduced the ability of females to attack and cannibalise the male. Virgin males
and females were paired and randomly allocated either to a control treatment, where females were allowed to attack and cannibalise
the male during copulation, or to an experimental treatment, where females were unable to cannibalise the male. The latter
was achieved by placing a paintbrush against her chelicerae during copulation. Our experimental manipulation did not affect
copulation duration or sperm storage. However, the number of sperm stored by the female increased with copulation duration
only if the male was cannibalised, suggesting that cannibalism increases relative paternity not only through prolonged copulation
duration following a fair raffle model but also through the cannibalism act itself. Future studies should explore whether
cannibalised males ejaculate more sperm or whether females selectively store the sperm of cannibalised males. 相似文献