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981.
Marcella Bassetto Pieter Leyssen Johan Neyts Mark M. Yerukhimovich David N. Frick Andrea Brancale 《Bioorganic & medicinal chemistry letters》2017,27(4):936-940
A ligand-based approach was applied to screen in silico a library of commercially available compounds, with the aim to find novel inhibitors of the HCV replication starting from the study of the viral NS3 helicase. Six structures were selected for evaluation in the HCV subgenomic replicon assay and one hit was found to inhibit the HCV replicon replication in the low micromolar range. A small series of new pyrrolone compounds was designed and synthesised, and novel structures were identified with improved antiviral activity. 相似文献
982.
983.
Désiré Collen Alfons Billiau Judith Edy Pieter De Somer 《Biochimica et Biophysica Acta (BBA)/General Subjects》1977,499(2):194-201
Mixed cultures of mouse fibroblasts and mouse fibroblasts transformed with Kirsten murine sarcoma virus were grown in petri dishes and overlayed with casein. The appearance of focal lysis zones required the presence of transformed cells in the culture and plasminogen in the overlay, indicating that caseinolysis was due to plasminogen activator released by the malignant cells. Caseinolysis was inhibited by addition of human plasma or bovine pancreatic trypsin inhibitor to the overlay, 1 ml of plasma being equivalent to 67 ± 18 (mean ± S.E.) kallikrein inhibitor (KI) units of trypsin inhibitor.The culture fluid of a human melanoma line induced lysis of a fibrin clot, 1 ml of culture fluid being equivalent to 250 CTA units of urokinase (EC 3.4.99.26). Fibrinolysis was inhibited by addition of human plasma or trypsin inhibitor, 1 ml of plasma being equivalent to 94 ± 34 KI units of trypsin inhibitor.Specific removal of antiplasmin, the fast-reacting plasmin inhibitor (Collen, D. (1976) Eur. J. Biochem. 69, 209), from plasma by immunoabsorption completely abolished its inhibitory activity, both in the caseinolytic and fibrinolytic assays. It is therefore concluded that antiplasmin is the only protein in human plasma capable of inhibiting the fibrinolytic activity associated with oncogenic transformation or neoplasia. Whether this effect is exclusively due to inhibition of formed plasmin or also to interference with plasminogen activvtion remains unsettled. 相似文献
984.
Pieter J. Bakker Angelique M. Scantlebery Loes M. Butter Nike Claessen Gwendoline J. D. Teske Tom van der Poll Sandrine Florquin Jaklien C. Leemans 《PloS one》2015,10(9)
Ischemia reperfusion injury is a common cause of acute kidney injury and is characterized by tubular damage. Mitochondrial DNA is released upon severe tissue injury and can act as a damage-associated molecular pattern via the innate immune receptor TLR9. Here, we investigated the role of TLR9 in the context of moderate or severe renal ischemia reperfusion injury using wild-type C57BL/6 mice or TLR9KO mice. Moderate renal ischemia induced renal dysfunction but did not decrease animal well-being and was not regulated by TLR9. In contrast, severe renal ischemia decreased animal well-being and survival in wild-type mice after respectively one or five days of reperfusion. TLR9 deficiency improved animal well-being and survival. TLR9 deficiency did not reduce renal inflammation or tubular necrosis. Rather, severe renal ischemia induced hepatic injury as seen by increased plasma ALAT and ASAT levels and focal hepatic necrosis which was prevented by TLR9 deficiency and correlated with reduced circulating mitochondrial DNA levels and plasma LDH. We conclude that TLR9 does not mediate renal dysfunction following either moderate or severe renal ischemia. In contrast, our data indicates that TLR9 is an important mediator of hepatic injury secondary to ischemic acute kidney injury. 相似文献
985.
C. P. E. Van der Logt P. M. C. Kluck J. Wiegant J. E. Landegent P. H. Reitsma 《Human genetics》1992,89(5):577-578
Summary The potential usefulness of the tissue factor pathway inhibitor gene for construction of physical and genetic linkage maps of chromosome 2 is reported. 相似文献
986.
Push–pull networks, in which two antagonistic enzymes control the
activity of a messenger protein, are ubiquitous in signal transduction pathways.
A classical example is the chemotaxis system of the bacterium
Escherichia coli, in which the kinase CheA and the
phosphatase CheZ regulate the phosphorylation level of the messenger protein
CheY. Recent experiments suggest that both the kinase and the phosphatase are
localized at the receptor cluster, and Vaknin and Berg recently demonstrated
that the spatial distribution of the phosphatase can markedly affect the
dose–response curves. We argue, using mathematical modeling, that the
canonical model of the chemotaxis network cannot explain the experimental
observations of Vaknin and Berg. We present a new model, in which a small
fraction of the phosphatase is localized at the receptor cluster, while the
remainder freely diffuses in the cytoplasm; moreover, the phosphatase at the
cluster has a higher binding affinity for the messenger protein and a higher
catalytic activity than the phosphatase in the cytoplasm. This model is
consistent with a large body of experimental data and can explain many of the
experimental observations of Vaknin and Berg. More generally, the combination of
differential affinity and catalytic activity provides a generic mechanism for
amplifying signals that could be exploited in other two-component signaling
systems. If this model is correct, then a number of recent modeling studies,
which aim to explain the chemotactic gain in terms of the activity of the
receptor cluster, should be reconsidered. 相似文献
987.
In a growth experiment at potassium levels varying between 0.001 m M and 3.0 m M potassium, relative growth rate (RGR) and other growth parameters were determined in Carex species: C. rostrata Stokes, C. limosa L., C. lasiocarpa Ehrh., C. diandra Schrank and C. acutiformis Ehrh., listed in order of increasing nutrient availability of their habitats. Carex species of nutrient poor sites did grow faster at low potassium concentration than species from nutrient rich habitats. The RGR of C. limosa was not affected by the K concentration, even at the lowest potassium concentration (0.001) m M ) used. At high potassium availability Carex species from nutrient-rich sites responded with greatly increased RGR, whereas the Carex from nutrient-poor sites absorbed potassium in excess of immediate growth requirements: luxury consumption. A comparison is made of the physiology of the Carex species as affected by stress and abundance of phosphate and potassium. 相似文献
988.
989.
Freezing of spinach leaf discs ( Spinacia aleracea L. cv. Estivato) resulted in an irreversible and parallel loss of protein-sulfhydryl (SH) and water-soluble protein. This decrease was inversely related to the increase in freezing injury as determined by the loss of electrolytes from the tissue after thawing. Loss of proteins and protein-SH occurred during freezing of the tissue and was not enhanced by thawing. The parallel decreases in content of soluble proteins and SH groups make it impossible to determine whether oxidation of protein-SH groups is the primary step in decline of protein content. During freezing the content of non-protein-SH compounds, mainly glutathione (GSH), was decreased to a lesser extent than that of protein-SH. Contrary to protein-SH, the levels of non-protein-SH declined substantially after thawing. The data indicate that GSH is not directly involved in protection of soluble proteins against freezing-induced denaturation. 相似文献
990.
J.Peter Gergen Joel Y. Loewenberg Pieter C. Wensink 《Journal of molecular biology》1981,147(4):475-499
We have isolated segments of Drosophila melanogaster DNA that contain two clusters of tRNA2Lys genes. In one segment, pPW511, there is a cluster of three of these genes surrounded by other tRNA genes. Two other segments, pPW516 and pPW541. share a 3 × 103 base-pair region that has a cluster of four tRNA2Lys genes. This cluster is flanked by 20 × 103 base-pairs of DNA that does not appear to have other tRNA genes. The tRNA genes in both clusters are irregularly spaced and are intermingled with moderately repetitive DNA. Each cluster is present once or perhaps twice in the haploid genome and has the same arrangement of restriction endonuclease sites in the genomic DNA as in the isolated, cloned DNA. In situ hybridization to polytene chromosomes localized the pPW511 cluster to the 42A region and the pPW516/541 cluster to the 42E region. Another region, 50B, also contains tRNA2Lys genes. In sum, these cloned tRNA2Lys genes account for most of this gene family and are irregularly spaced in two clusters. 相似文献