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Since bone morphogenetic proteins (BMPs) play an important role in melanoma progression, we aimed to determine the molecular mechanisms leading to overexpression of BMP4 in melanoma cells compared to normal melanocytes. With our experimental approach we revealed that loss of expression of a microRNA represents the starting point for a signaling cascade finally resulting in overexpression of BMP4 in melanoma cells. In detail, strongly reduced expression of the microRNA miR-196a in melanoma cells compared to healthy melanocytes leads to enhanced HOX-B7 mRNA and protein levels, which subsequently raise Ets-1 activity by inducing basic fibroblast growth factor (bFGF). Ets-1 finally accounts for induction of BMP4 expression. We were furthermore able to demonstrate that bFGF-mediated induction of migration is achieved via activation of BMP4, thus determining BMP4 as major modulator of migration in melanoma. In summary, our study provides insights into the early steps of melanoma progression and might thereby harbor therapeutic relevance.  相似文献   

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Hepatitis B virus-like particles (including DANE particles) with DNA polymerase activity but negative for HBs Ag have been identified in NON-A, NON-B hepatitis sera positive for HC Ag. Although specifically associated with the particles, HC Ag is not a surface antigen of the hepatitis C virus identified here for the first time. The relationship of this agent with HBV seems obvious, and deserves further study.  相似文献   

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The use of our mink cell line maintained in vitro infected with the murine xenotropic AT 124 virus, and that of a (W/Fu x bn) f1 rat anti-124 serum allow us to define a new cell surface antigen specific of murine xenotropic type C viruses.  相似文献   

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Major antigenic identity has been demonstrated by immunodiffusion between the Ag described by Shirachi and confirmed by us (NANB/e) in the serum on non A non B hepatitis and the HBe/3 specificity of hepatitis B virus (HBV). A second Ag (NANB/c) linked to the core of a new virion morphologically similar to HBV and also associated with ADN polymerase activity as recently described, has been identified and purified from an infected liver. This NANB/c Ag also cross reacts with HBc Ag. These results confirm that HBV and the NANB virus defined here belong to the same new class of DNA viruses.  相似文献   

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Summary The title compound, a metabolite of 4,5,6,7-tetrahydrobenzo[b]thien-4-ylurea, was synthesized and found to be an effective growth promoter in sheep, mice, and rats. In sheep it gave over a 6-week growth period at 15 and 60 ppm in the diet an economically and statistically significant growth response.United States adopted name (USAN).We thank Dr T.J. Bentley, D.J. France, and Dr L.D. Spicer for synthesis and structural elucidation work, Dr M.W. Bullock and G.W. Cox for metabolism studies, Drs J. Harter, D. Ingle, J.M. Pensack and L. Wozniak and their associates for biological data, and Drs D.J. Thoennes and M.L. Thomson for spectral data and interpretations.  相似文献   

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Like most positive-strand RNA viruses, hepatitis C virus (HCV) forms a membrane-associated replication complex consisting of replicating RNA, viral and host proteins anchored to altered cell membranes. We used a combination of qualitative and quantitative electron microscopy (EM), immuno-EM, and the 3D reconstruction of serial EM sections to analyze the host cell membrane alterations induced by HCV. Three different types of membrane alteration were observed: vesicles in clusters (ViCs), contiguous vesicles (CVs), and double-membrane vesicles (DMVs). The main ultrastructural change observed early in infection was the formation of a network of CVs surrounding the lipid droplets. Later stages in the infectious cycle were characterized by a large increase in the number of DMVs, which may be derived from the CVs. These DMVs are thought to constitute the membranous structures harboring the viral replication complexes in which viral replication is firmly and permanently established and to protect the virus against double-stranded RNA-triggered host antiviral responses.  相似文献   

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G Asato  R D Wilbur 《Experientia》1979,35(11):1458-1459
The title compound, a metabolite of 4,5,6,7-tetrahydrobenzo[b]thien-4-ylurea, was synthesized and found to be an effective growth promoter in sheep, mice, and rats. In sheep it gave over a 6-week growth period at 15 and 60 ppm in the diet an economically and statistically significant growth response.  相似文献   

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Ribavirin, a broad spectrum antiviral agent, in conjunction with interferon forms the current standard of treatment for hepatitis C virus (HCV) infection in humans. While ribavirin alone fails to induce a significant antiviral response, in combination with interferon, ribavirin dramatically improves the long-term outcome of therapy. The predominant mechanism(s) of ribavirin action against HCV, are yet to be established. In this review, we examine the current status of our understanding of the metabolism, pharmacokinetics and mechanisms of the antiviral activity of ribavirin against HCV, all of which are central to the rational identification of improved treatment protocols. Received 30 September 2005; received after revision 20 November 2005; accepted 7 December 2005  相似文献   

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Résumé L'acide oxamyl-hydroxamique, l'acide salicylhydroxamique et l'acétoxyoxamide inhibent la reproduction du bactériophage T4 dans l'Escherichia coli B. L'activité de chacun de ces composés était plus grande que celle de l'hydroxyurée dans le même système d'essai. De ce fait, une évaluation plus poussée de ces 3 agents ainsi que d'autres acides hydroxamiques dans une série de systèmes d'essai sur les virus paraît clairement indiquée.  相似文献   

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Abnormalities of platelet functions have been linked to reelin-impaired neuronal disorders. However, little attention has been given to understanding the interplay between reelin and platelet. In this study, reelin was found to present in the human platelets and megakaryocyte-like leukemic cells. Reelin-binding assays revealed that extracellular reelin can interact with platelets through the receptor belonging to the low density lipoprotein receptor gene family. The reelin-to-platelet interactions enhance platelet spreading on fibrinogen concomitant with the augmentation of lamellipodia formation and F-actin bundling. In contrast, reelin has no effect on integrin αIIbβ3 activation and agonist-induced platelet aggregation. Molecular analysis revealed that the up-regulation of Rac1 activity and the inhibition of protein kinase C δ-Thr505 phosphorylation are important for reelin-mediated enhancement of platelet spreading on fibrinogen. These findings demonstrate for the first time that reelin is present in platelets and the reelin-to-platelet interactions play a novel role in platelet signaling and functions.  相似文献   

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The production of virions by Chinese hamster kidney cells infected with SV 40 DNA is increased 10 to 100 fold by mitomycin C treatment. This observation has been confirmed for different cell clones. The optimum concentration of mitomycin C has been determined.  相似文献   

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Traumatic brain injury (TBI) initiates molecular and cellular pathologies that underlie post-injury morbidities, including hippocampus-related memory decline and epileptogenesis. Non-coding small RNAs are master regulators of gene expression with the potential to affect multiple molecular pathways. To evaluate whether hippocampal gene expression networks are chronically regulated by microRNAs after TBI, we sampled the dentate gyrus of rats with severe TBI induced by lateral fluid-percussion injury 3 months earlier. Ingenuity pathway analysis revealed 30 upregulated miR-124-3p targets, suggesting that miR-124-3p is downregulated post-TBI (z-score?=?? 5.146, p?<?0.05). Droplet digital polymerase chain reaction (ddPCR) and in situ hybridization confirmed the chronic downregulation of miR-124-3p (p?<?0.05). Quantitative PCR analysis of two targets, Plp2 and Stat3, indicated that their upregulation correlated with the miR-124-3p downregulation (r?=?? 0.647, p?<?0.05; r?=?? 0.629, p?<?0.05, respectively). Immunohistochemical staining of STAT3 confirmed the increased protein expression. STRING analysis showed that 9 of the 30 miR-124-3p targets belonged to a STAT3 network. Reactome analysis and data mining connected the targets especially to inflammation and signal transduction. L1000CDS2 software revealed drugs (e.g., importazole, trichostatin A, and IKK-16) that could reverse the observed molecular changes. The translational value of our data was emphasized by in situ hybridization showing chronic post-traumatic downregulation of miR-124-3p in the dentate gyrus of TBI patients. Analysis of another brain injury model, status epilepticus, highlighted the fact that chronic downregulation of miR-124 is a common phenomenon after brain injury. Together, our findings indicate that miR-124-3p is a chronic modulator of molecular networks relevant to post-injury hippocampal pathologies in experimental models and in humans.  相似文献   

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