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131.
132.
Min JH Yang H Ivan M Gertler F Kaelin WG Pavletich NP 《Science (New York, N.Y.)》2002,296(5574):1886-1889
The ubiquitination of the hypoxia-inducible factor (HIF) by the von Hippel-Lindau tumor suppressor (pVHL) plays a central role in the cellular response to changes in oxygen availability. pVHL binds to HIF only when a conserved proline in HIF is hydroxylated, a modification that is oxygen-dependent. The 1.85 angstrom structure of a 20-residue HIF-1alpha peptide-pVHL-ElonginB-ElonginC complex shows that HIF-1alpha binds to pVHL in an extended beta strand-like conformation. The hydroxyproline inserts into a gap in the pVHL hydrophobic core, at a site that is a hotspot for tumorigenic mutations, with its 4-hydroxyl group recognized by buried serine and histidine residues. Although the beta sheet-like interactions contribute to the stability of the complex, the hydroxyproline contacts are central to the strict specificity characteristic of signaling. 相似文献
133.
The numbers of rat glossopharyngeal and chorda tympani fibers responding to one, two, three, or four taste stimuli of different quality (sodium chloride, hydrochloric acid, quinine, and sucrose) and to each of the six possible pairs of these stimuli can be predicted if there are four independent sensitivities randomly distributed among innervating fibers. 相似文献
134.
Action spectra were determined for lightinduced phase shifts of the circadian rhythm of adult emergence in Drosophila pseudoobscura. The action spectra for advance and delay phase shifts are similar; the most effective wavelengths are in the blue region, with a sharp cutoff above 500 nanometers. This similarity suggests that the same photoreceptive pigment mediates both advance and delay phase shifts. 相似文献
135.
Rats maintained on a low phosphorus diet supplemented with 25-hydroxyvitamin D(3) show high intestinal calcium transport activity as compared to rats similarly treated but fed a diet containing adequate phosphorus. This increased transport activity is correlated with an increased biosynthesis of 1,25-dihydroxyvitamin D(3), the probable metabolically active form of the vitamin in the intestine. 相似文献
136.
Inhibition of the complement cascade by the major secretory protein of vaccinia virus 总被引:28,自引:0,他引:28
The complement system contributes to host defenses against invasion by infectious agents. A 35-kilodalton protein, encoded by vaccinia virus and secreted from infected cells, has sequence similarities to members of a gene family that includes complement control proteins. Biochemical and genetic studies showed that the viral protein binds to derivatives of the fourth component of complement and inhibits the classical complement cascade, suggesting that it serves as a defense molecule to help the virus evade the consequences of complement activation. 相似文献
137.
Rolef Ben-Shahar T Heeger S Lehane C East P Flynn H Skehel M Uhlmann F 《Science (New York, N.Y.)》2008,321(5888):563-566
Replicated chromosomes are held together by the chromosomal cohesin complex from the time of their synthesis in S phase onward. This requires the replication fork-associated acetyl transferase Eco1, but Eco1's mechanism of action is not known. We identified spontaneous suppressors of the thermosensitive eco1-1 allele in budding yeast. An acetylation-mimicking mutation of a conserved lysine in cohesin's Smc3 subunit makes Eco1 dispensable for cell growth, and we show that Smc3 is acetylated in an Eco1-dependent manner during DNA replication to promote sister chromatid cohesion. A second set of eco1-1 suppressors inactivate the budding yeast ortholog of the cohesin destabilizer Wapl. Our results indicate that Eco1 modifies cohesin to stabilize sister chromatid cohesion in parallel with a cohesion establishment reaction that is in principle Eco1-independent. 相似文献
138.
Ranson H Claudianos C Ortelli F Abgrall C Hemingway J Sharakhova MV Unger MF Collins FH Feyereisen R 《Science (New York, N.Y.)》2002,298(5591):179-181
The emergence of insecticide resistance in the mosquito poses a serious threat to the efficacy of many malaria control programs. We have searched the Anopheles gambiae genome for members of the three major enzyme families- the carboxylesterases, glutathione transferases, and cytochrome P450s-that are primarily responsible for metabolic resistance to insecticides. A comparative genomic analysis with Drosophila melanogaster reveals that a considerable expansion of these supergene families has occurred in the mosquito. Low gene orthology and little chromosomal synteny paradoxically contrast the easily identified orthologous groups of genes presumably seeded by common ancestors. In A. gambiae, the independent expansion of paralogous genes is mainly a consequence of the formation of clusters among locally duplicated genes. These expansions may reflect the functional diversification of supergene families consistent with major differences in the life history and ecology of these organisms. These data provide a basis for identifying the resistance-associated enzymes within these families. This will enable the resistance status of mosquitoes, flies, and possibly other holometabolous insects to be monitored. The analyses also provide the means for identifying previously unknown molecules involved in fundamental biological processes such as development. 相似文献
139.
140.
Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo 总被引:1,自引:0,他引:1
Microglial cells represent the immune system of the mammalian brain and therefore are critically involved in various injuries and diseases. Little is known about their role in the healthy brain and their immediate reaction to brain damage. By using in vivo two-photon imaging in neocortex, we found that microglial cells are highly active in their presumed resting state, continually surveying their microenvironment with extremely motile processes and protrusions. Furthermore, blood-brain barrier disruption provoked immediate and focal activation of microglia, switching their behavior from patroling to shielding of the injured site. Microglia thus are busy and vigilant housekeepers in the adult brain. 相似文献