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161.
Ahsen Ov Voigtmann U Klotz M Nifantiev N Schottelius A Ernst A Müller-Tiemann B Parczyk K 《Analytical biochemistry》2008,372(1):96-105
Fucosyltransferase VII (FucTVII) is a very promising drug target for treatment of inflammatory skin diseases. Its activity is required for synthesis of the sialyl-Lewis X glycoepitopes on the E- and P-selectin ligands, necessary for lymphocyte migration into the skin. High-throughput screening (HTS) of large chemical libraries has become the main source of novel chemical entities for the pharmaceutical industry. The screening of very large compound collections requires the use of specialized assay techniques that minimize time and costs. We describe the development of a miniaturized scintillation proximity assay for human FucTVII based on a oligosaccharide acceptor substrate that is identical to the glycosylation of the physiological substrate. In addition to assay development, the assay performance in a HTS campaign is shown. We screened 798,131 compounds from the Schering AG HTS library and identified 233 IC50 hits; 229 hits were FucTVII specific in so far as they did not inhibit either alpha-fucosidase or galactosyltransferase. In addition to screening a drug-like small-molecule collection, we worked on rational approaches to develop inhibitors or glycosidic decoys based on oligosaccharide-substrate analogues. The structure-activity relationship observed thereby is very narrow and shows strict requirements that are consistent with the described substrate specificity of FucTVII. 相似文献
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Martin Scaal Felicitas Pr?ls Ernst Martin Füchtbauer Ketan Patel Christoph Hornik Thomas K?hler Bodo Christ Beate Brand-Saberi 《Mechanisms of development》2002,110(1-2):51-60
Bone morphogenetic protein (BMP) signaling is known to be involved in multiple inductive events during embryogenesis including the development of amniote skin. Here, we demonstrate that early application of BMP-2 to the lateral trunk of chick embryos induces the formation of dense dermis, which is competent to participate in feather development. We show that BMPs induce the dermis markers Msx-1 and cDermo-1 and lead to dermal proliferation, to expression of β-catenin, and eventually to the formation of ectopic feather tracts in originally featherless regions of chick skin. Moreover, we present a detailed analysis of cDermo-1 expression during early feather development. The data implicate that cDermo-1 is located downstream of BMP in a signaling pathway that leads to condensation of dermal cells. The roles of BMP and cDermo-1 during development of dermis and feather primordia are discussed. 相似文献
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Summary Steroid sulfatase (STS) activities in female fibroblast strains are significantly higher than in male strains, as determined by cleavage of dehydroepiandrosterone sulfate. The difference is probably not due to hormonal control of gene expression, but suggests that for this X-linked locus there is no gene dosage compensation. 相似文献
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168.
Karl G. Lickfeld Beate Menge Babbara Hohn Thomas Hohn 《Journal of molecular biology》1976,103(2):299-318
Quantitative measurements on number, size, shape, location and time of appearance of heads and head-related structures in thin sections of induced bacteriophage λ lysogens were performed. Three types of particles can be distinguished: empty heads with a mean diameter of 39 nm (petit λ), heads partially filled with DNA with a mean diameter of 51 nm (grizzled particles) and particles filled with DNA, having a diameter of 47 nm (black particles). Some of the latter ones can be seen with a tail attached. The particles first to appear are the petit λ. A few minutes later grizzled and black particles can be seen. This sequence correspons to measurements of biological activities in lysates, i.e. to plaque-forming units, and to the number of particles which can be packaged with DNA and transformed in vitro to plaque-forming particles, respectively.DNA packaging seems to occur on the boundary area between cytoplasm and DNA plasm. Tails, on the other hand, accumulate near the cytoplasmic membrane.Two steps in DNA packaging can be distinguished, since one type of mutant blocked in DNA packaging (amber in gene A) produces paracrystalline agglomerations of petit λ and clusters of tails while another (amber in gene D) produces grizzled particles in addition. 相似文献
169.
Matthew Pettengill Simon Robson Megan Tresenriter José Luis Millán Anny Usheva Taiese Bingham Mirjam Belderbos Ilana Bergelson Sarah Burl Beate Kampmann Laura Gelinas Tobias Kollmann Louis Bont Ofer Levy 《The Journal of biological chemistry》2013,288(38):27315-27326
Extracellular adenosine, a key regulator of physiology and immune cell function that is found at elevated levels in neonatal blood, is generated by phosphohydrolysis of adenine nucleotides released from cells and catabolized by deamination to inosine. Generation of adenosine monophosphate (AMP) in blood is driven by cell-associated enzymes, whereas conversion of AMP to adenosine is largely mediated by soluble enzymes. The identities of the enzymes responsible for these activities in whole blood of neonates have been defined in this study and contrasted to adult blood. We demonstrate that soluble 5′-nucleotidase (5′-NT) and alkaline phosphatase (AP) mediate conversion of AMP to adenosine, whereas soluble adenosine deaminase (ADA) catabolizes adenosine to inosine. Newborn blood plasma demonstrates substantially higher adenosine-generating 5′-NT and AP activity and lower adenosine-metabolizing ADA activity than adult plasma. In addition to a role in soluble purine metabolism, abundant AP expressed on the surface of circulating neonatal neutrophils is the dominant AMPase on these cells. Plasma samples from infant observational cohorts reveal a relative plasma ADA deficiency at birth, followed by a gradual maturation of plasma ADA through infancy. The robust adenosine-generating capacity of neonates appears functionally relevant because supplementation with AMP inhibited whereas selective pharmacologic inhibition of 5′-NT enhanced Toll-like receptor-mediated TNF-α production in neonatal whole blood. Overall, we have characterized previously unrecognized age-dependent expression patterns of plasma purine-metabolizing enzymes that result in elevated plasma concentrations of anti-inflammatory adenosine in newborns. Targeted manipulation of purine-metabolizing enzymes may benefit this vulnerable population. 相似文献
170.
Elisa Villa Aleksander S. Alekseev James E. Barrick Darwin R. Boardman Alexandra V. Djenchuraeva Beate Fohrer Holger Forke Natalya V. Goreva Philip H. Heckel Tatiana N. Isakova Olga Kossovaya Lance L. Lambert María-Luisa Martínez-Chacn Carlos A. Mndez Tamara I. Nemyrovska Svetlana Remizova Elias Samankassou Luis C. Snchez de Posada Katsumi Ueno Greg Wahlman David M. Work 《Palaeoworld》2009,18(2-3):114-119
Studies carried out for more than 10 years by the Task Group to establish GSSPs at the base of the Moscovian–Kasimovian and Kasimovian–Gzhelian boundaries have resulted in the proposal that the level at which the conodont species Idiognathodus simulator (Ellison, 1941) first appears be selected to mark the base of the Gzhelian Stage. This expands this eastern European chronostratigraphic unit to a global scale.I. simulator (sensu Barrick et al., 2008) has been identified so far in Midcontinent and eastern North America, the Moscow and Donets basins and southern Urals of eastern Europe, and in south-central China. Correlation of this level based on this species and other conodont species can be reinforced in some areas by ammonoid and fusulinid data. 相似文献