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991.
Miyazaki Y Matsunaga S Tang J Maeda Y Nakano M Philippe RJ Shibahara M Liu W Sato H Wang L Nolte RT 《Bioorganic & medicinal chemistry letters》2005,15(9):2203-2207
A novel class of furo[2,3-d]pyrimidines has been discovered as potent dual inhibitors of Tie-2 and VEGFR2 receptor tyrosine kinases (TK) and a diarylurea moiety at 5-position shows remarkably enhanced activity against both enzymes. One of the most active compounds, 4-amino-3-(4-((2-fluoro-5-(trifluoromethyl)phenyl)amino-carbonylamino)phenyl)-2-(4-methoxyphenyl)furo[2,3-d]pyrimidine (7k) is <3 nM on both TK receptors and the activity is rationalized based on the X-ray crystal structure. 相似文献
992.
Zhou CZ Meyer P Quevillon-Cheruel S Li De La Sierra-Gallay I Collinet B Graille M Blondeau K François JM Leulliot N Sorel I Poupon A Janin J Van Tilbeurgh H 《Protein science : a publication of the Protein Society》2005,14(1):209-215
We determined the three-dimensional crystal structure of the protein YML079wp, encoded by a hypothetical open reading frame from Saccharomyces cerevisiae to a resolution of 1.75 A. The protein has no close homologs and its molecular and cellular functions are unknown. The structure of the protein is a jelly-roll fold consisting of ten beta-strands organized in two parallel packed beta-sheets. The protein has strong structural resemblance to the plant storage and ligand binding proteins (canavalin, glycinin, auxin binding protein) but also to some plant and bacterial enzymes (epimerase, germin). The protein forms homodimers in the crystal, confirming measurements of its molecular mass in solution. Two monomers have their beta-sheet packed together to form the dimer. The presence of a hydrophobic ligand in a well conserved pocket inside the barrel and local sequence similarity with bacterial epimerases may suggest a biochemical function for this protein. 相似文献
993.
Phylogeography and demography of Guianan harlequin toads (Atelopus): diversification within a refuge
We investigated the genetic structure of populations of Guianan harlequin toads (genus Atelopus) and their evolutionary affinities to extra-Guianan congeners. Phylogenetic analysis of mitochondrial cytochrome b (cyt b) and NADH dehydrogenase subunit 2 (ND2) gene sequences produced well-supported clades largely corresponding to the four recognized taxa in the Guianas (Atelopus spumarius hoogmoedi, Atelopus spumarius barbotini, Atelopus franciscus, and Atelopus flavescens). Our findings suggest that the Guianan A. spumarius represent distinct evolutionary lineages that merit distinction from Amazonian conspecifics, and that the status of A. flavescens and A. franciscus is somewhat less clear. Approximately 69% of the observed genetic variation is accounted for by differences between these four recognized taxa. Coalescent-based estimates of gene flow between taxa suggest that these lineages are largely isolated from one another. Negligible rates of migration between populations and significant divergence within such close proximity suggests that although the region inhabited by these taxa is almost entirely undisturbed, significant habitat heterogeneity exists as to have produced a remarkable diversification of Atelopus within the eastern Guiana Shield. These results contradict the commonly held view of the Guiana Shield as a 'refuge' whose stability during late Tertiary and Quaternary climatic fluctuations served as a biotic reservoir. Instead, we provide evidence that climatic fluctuations during this time had a diversifying effect within the Guianan region. 相似文献
994.
Wolbachia is a group of maternally inherited endosymbiotic bacteria that infect and induce cytoplasmic incompatibility (CI) in a wide range of arthropods. In contrast to other species, the mosquito Culex pipiens displays an extremely high number of CI types suggesting differential infection by multiple Wolbachia strains. Attempts so far failed to detect Wolbachia polymorphism that might explain this high level of CI diversity found in C. pipiens populations. Here, we establish that Wolbachia infection is near to or at fixation in worldwide populations of the C. pipiens complex. Wolbachia polymorphism was addressed by sequence analysis of the Tr1 gene, a unique transposable element of the IS5 family, which allowed the identification of five C. pipiens Wolbachia strains, differing either by nucleotide substitution, presence or absence pattern, or insertion site. Sequence analysis also showed that recombination, transposition and superinfection occurred at very low frequencies. Analysis of the geographical distributions of each Wolbachia strain among C. pipiens populations indicated a strong worldwide differentiation independent from mosquito subspecies type, except in the UK. The availability of this polymorphic marker now opens the way to investigate evolution of Wolbachia populations and CI dynamics, in particular in regions where multiple crossing types coexist among C. pipiens populations. 相似文献
995.
Taupin P 《Médecine sciences : M/S》2005,21(8-9):711-714
996.
Archer A Sauvaget D Chauffeton V Bouchet PE Chambaz J Pinçon-Raymond M Cardot P Ribeiro A Lacasa M 《Molecular endocrinology (Baltimore, Md.)》2005,19(9):2320-2334
In the small intestine, the expression of the apolipoprotein (apo) C-III and A-IV genes is restricted to the enterocytes of the villi. We have previously shown that, in transgenic mice, specific expression of the human apo C-III requires a hormone-responsive element (HRE) located in the distal region of the human apoA-IV promoter. This HRE binds the hepatic nuclear factors (HNF)-4alpha and gamma. Here, intraduodenal injections in mice and infections of human enterocytic Caco-2/TC7 cells with an adenovirus expressing a dominant-negative form of HNF-4alpha repress the expression of the apoA-IV gene, demonstrating that HNF-4 controls the apoA-IV gene expression in enterocytes. We show that HNF-4alpha and gamma functionally interact with a second HRE present in the proximal region of the human apoA-IV promoter. New sets of transgenic mice expressing mutated forms of the promoter, combined with the human apo C-III enhancer, demonstrate that, whereas a single HRE is sufficient to reproduce the physiological cephalo-caudal gradient of apoA-IV gene expression, both HREs are required for expression that is restricted to villi. The combination of multiple HREs may specifically recruit regulatory complexes associating HNF-4 and either coactivators in villi or corepressors in crypts. 相似文献
997.
Guy?BeugnonEmail author Jean-Paul?Lachaud Philippe?Chagné 《Journal of Insect Behavior》2005,18(3):415-432
We investigated how the formicine ant Gigantiops destructor can use vector information to navigate within the cluttered environment of the rain forest. Displaced foragers use skylight information to move in the theoretical feeder-to-nest direction, whether they are prevented from updating their path-integrator during foraging or captured at the departure from their nest, i.e. with a current accumulator state very close to zero. Only ants that have collected food are able to download a long-term stored reference vector pointing in the nest direction, irrespective of the current accumulator state of their path-integrator stored in a working memory and independent of familiar landmarks. Depending on the release sites, ants that became lost at a maximum distance of 50 cm could still hit and recognize their familiar route, or they engaged in a systematic search for it centered on the release sites. In contrast to Cataglyphis desert ants, Gigantiops ants do not rely primarily on the current accumulator state of their egocentric path integrator. Such a long-term vector-based navigation primed by food capture is well adapted for a tropical ant foraging during periods spanning several hours. This could prevent the numerous cumulative errors in the evaluation of the angles steered that might result from a continuously running path-integrator operating during complex foraging patterns performed at ground or arboreal levels and during passive displacement in response to heavy rain. 相似文献
998.
Dietary myristic acid at physiologically relevant levels increases the tissue content of C20:5 n-3 and C20:3 n-6 in the rat 总被引:1,自引:0,他引:1
This study was designed to investigate the effect of myristic acid on the biosynthesis and metabolism of highly unsaturated fatty acids, when it is supplied in a narrow physiological range in the diet of the rat (0.2-1.2% of total dietary energy). Three experimental diets were designed, containing 22% of total dietary energy as lipids and increasing doses of myristic acid (0.71, 3.00 and 5.57% of total fatty acids). Saturated fat did not exceed 31% of total fat and the C18:3 n-3 amount in each diet was strictly equal (1.6% of total fatty acids). After 7 weeks, the diets had no effect on plasma cholesterol level but greatly modified the liver, plasma and adipose tissue saturated, monounsaturated and polyunsaturated fatty acid profiles. Firstly, daily intakes of myristic acid resulted in a dose-dependent tissue accumulation of myristic acid itself. Palmitic acid was significantly increased in the tissues of the rats fed the higher dose of myristic acid. A dose-response accumulation of tissue C16:1 n-7 as a function of dietary C14:0 was also shown. Secondly, a main finding was that, among n-3 and n-6 polyunsaturated fatty acids, a dose-response accumulation of liver and plasma C20:5 n-3 and C20:3 n-6 (two precursors of eicosanoids) as a function of dietary C14:0 was shown. This result suggests that dietary myristic acid may participate in the regulation of highly unsaturated fatty acid biosynthesis and metabolism. 相似文献
999.
Mayaux P Holmgren P Achard F Eva H Stibig HJ Branthomme A 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2005,360(1454):373-384
Despite the importance of the world's humid tropical forests, our knowledge concerning their rates of change remains limited. Two recent programmes (FAO 2000 Forest Resources Assessment and TREES II), exploiting the global imaging capabilities of Earth observing satellites, have recently been completed to provide information on the dynamics of tropical forest cover. The results from these independent studies show a high degree of conformity and provide a good understanding of trends at the pan-tropical level. In 1990 there were some 1150 million ha of tropical rain forest with the area of the humid tropics deforested annually estimated at 5.8 million ha (approximately twice the size of Belgium). A further 2.3 million ha of humid forest is apparently degraded annually through fragmentation, logging and/or fires. In the sub-humid and dry tropics, annual deforestation of tropical moist deciduous and tropical dry forests comes to 2.2 and 0.7 million ha, respectively. Southeast Asia is the region where forests are under the highest pressure with an annual change rate of -0.8 to -0.9%. The annual area deforested in Latin America is large, but the relative rate (-0.4 to -0.5%) is lower, owing to the vast area covered by the remaining Amazonian forests. The humid forests of Africa are being converted at a similar rate to those of Latin America (-0.4 to -0.5% per year). During this period, secondary forests have also been established, through re-growth on abandoned land and forest plantations, but with different ecological, biophysical and economic characteristics compared with primary forests. These trends are significant in all regions, but the extent of new forest cover has proven difficult to establish. These results, as well as the lack of more detailed knowledge, clearly demonstrate the need to improve sound scientific evidence to support policy. The two projects provide useful guidance for future monitoring efforts in the context of multilateral environmental agreements and of international aid, trade and development partnerships. Methodologically, the use of high-resolution remote sensing in representative samples has been shown to be cost-effective. Close collaboration between tropical institutions and inter-governmental organizations proved to be a fruitful arrangement in the different projects. To properly assist decision-making, monitoring and assessments should primarily be addressed at the national level, which also corresponds to the ratification level of the multilateral environmental agreements. The Forest Resources Assessment 2000 deforestation statistics from countries are consistent with the satellite-based estimates in Asia and America, but are significantly different in Africa, highlighting the particular need for long-term capacity-building activities in this continent. 相似文献
1000.
Naip5/Birc1e and susceptibility to Legionella pneumophila 总被引:6,自引:0,他引:6
Genetic analysis in mice is a powerful approach for the identification of genes and proteins that have a key role at the interface of the host-pathogen interaction. The Lgn1 locus has been found to control the intracellular replication of Legionella pneumophila in murine macrophages. Using functional complementation in transgenic mice, the Naip5/Birc1e gene has been identified as responsible for the Lgn1 effect. The classification of Naip5/Birc1e as a member of the NLR protein family suggests that Naip5/Birc1e acts as an intracellular sensor of L. pneumophila. The nature of the signal transduced by Naip5/Birc1e in response to Legionella products is of great interest but is currently unknown. Here, several possible scenarios are presented. 相似文献