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51.
52.
Tumor cell alpha3beta1 integrin and vascular laminin-5 mediate pulmonary arrest and metastasis 下载免费PDF全文
Wang H Fu W Im JH Zhou Z Santoro SA Iyer V DiPersio CM Yu QC Quaranta V Al-Mehdi A Muschel RJ 《The Journal of cell biology》2004,164(6):935-941
Arrest of circulating tumor cells in distant organs is required for hematogenous metastasis, but the tumor cell surface molecules responsible have not been identified. Here, we show that the tumor cell alpha3beta1 integrin makes an important contribution to arrest in the lung and to early colony formation. These analyses indicated that pulmonary arrest does not occur merely due to size restriction, and raised the question of how the tumor cell alpha3beta1 integrin contacts its best-defined ligand, laminin (LN)-5, a basement membrane (BM) component. Further analyses revealed that LN-5 is available to the tumor cell in preexisting patches of exposed BM in the pulmonary vasculature. The early arrest of tumor cells in the pulmonary vasculature through interaction of alpha3beta1 integrin with LN-5 in exposed BM provides both a molecular and a structural basis for cell arrest during pulmonary metastasis. 相似文献
53.
Pseudomonas fluorescens strain GRS1, PRS9 and their cold tolerant mutants were examined for their tricalcium phosphate (TCP) solubilizing activity in NBRIP (broth) media at 10°C and 25°C. Invariably, all the cold tolerant mutants of GRS1 and PRS9 were found more efficient than their respective wild type counterparts for ‘P’ solubilization activity at 10°C as compared to 25°C. ‘P’ solubilization potential of CRM was found maximum among all the strains followed by CRPF6 and CRPF4. To the best of out knowledge, this is the first report regarding low temperature ‘P’ solubilization activity. 相似文献
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A galactose-specific adhesin was isolated from the fimbriae of an enteroaggregative Escherichia coli (EAEC) strain. The adhesin was found to be a high molecular weight aggregate of the 18-kDa monomer. The dimeric (36 kDa)
and tetrameric (76 kDa) forms appeared in sodium dodecyl sulphate polyacrylamide gel electrophoresis when a higher concentration
of the adhesin was used. The IgGAD (IgG against adhesin) obtained from the immune sera raised in rabbits against purified adhesin could detect all three forms
of the adhesin even from the crude fimbrial preparation. The IgGAD failed to recognize the adhesin in the presence of galactose, thereby suggesting the antibody-binding site and the sugar-binding
site on the adhesin might be same or overlapping. Furthermore, the IgGAD could localize the adhesin exclusively on the fimbriae as observed in immunogold electron microscopy. The aggregative adherence
of the bacteria to HEp-2 cells was reduced to 70% in the presence of the IgGAD. A glycoprotein (34 kDa) present in the membrane fraction of HEp-2 cells interacted with the purified adhesin in a galactose-specific
manner. The IgGAD could recognize the adhesin from the crude fimbrial preparation of 9 out of 10 clinical isolates of EAEC strains but failed
to identify any protein from the crude fimbrial preparation of Salmonella typhimurium (fim +ve as well as fim −ve strain), Vibrio cholerae (WO7) or Escherichia coli DH5α. 相似文献
56.
Phage display is the longest-standing platform among molecular display technologies. Recent developments have extended its utility to proteins that were previously recalcitrant to phage display. The technique has played a dominant role in forming the field of synthetic binding protein engineering, where novel interfaces have been generated from libraries built using antibody fragment frameworks and also alternative scaffolds. Combinatorial methods have also been developed for the rapid analysis of binding energetics across protein interfaces. The ability to rapidly select and analyze binding interfaces, and compatibility with high-throughput methods under diverse conditions, makes it likely that the combination of phage display and synthetic combinatorial libraries will prove to be the method of choice for synthetic binding protein engineering for broad applications. 相似文献
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Harrison BA Fernández H Chandan V Schuster MW Rademacher LO Toledo C Li J Altman E 《Helicobacter》2011,16(6):459-467
Background: The outer core region of H. pylori lipopolysaccharide (LPS) contains α1,6‐glucan previously shown to contribute to colonizing efficiency of a mouse stomach. The aim of the present study was to generate monoclonal antibodies (mAbs) specific for α1,6‐glucan and characterize their binding properties and functional activity. Materials and Methods: BALB/c mice were injected intraperitoneally with 108 formalin‐fixed H. pylori O:3 0826::Kan cells 3× over 56 days to achieve significant titer. Anti‐α1,6‐glucan‐producing hybridomas were screened by indirect ELISA using purified H. pylori O:3 0826::Kan LPS. One clone, 1C4F9, was selected for further characterization. The specificities of mAbs were determined by indirect and inhibition ELISA using structurally defined H. pylori LPS and synthetic oligosaccharides, and whole‐cell indirect ELISA (WCE) of clinical isolates. They were further characterized by indirect immunofluorescent (IF) microscopy and their functional activity in vitro determined by serum bactericidal assays against wild‐type and mutant strains of H. pylori. Results: The generated anti‐α1,6‐glucan IgM, 1C4F9, has demonstrated an excellent specificity for the glucan chain containing 5 to 6 α1,6‐linked glucose residues and showed surface accessibility by IF microscopy with H. pylori cells adherent to gastric adenocarcinoma cells monolayers. Of 38 isolates from Chile, 17 strains reacted with antiglucan mAbs in WCE (OD450 ≥ 0.2). Bactericidal activity was observed against selective wild‐type and mutant H. pylori strains exhibiting OD450 values of ≥0.45 in WCE. Conclusions: Anti‐α1,6‐glucan mAbs could have potential application in typing and surveillance of H. pylori isolates as well as offer insights into structural requirements for the development of LPS‐based vaccine against H. pylori infections. 相似文献
59.
Frank Butty Marta Wierzbicka Erik Verschueren Peter Vanhee Haiming Huang Andreas Ernst Nisa Dar Igor Stagljar Luis Serrano Sachdev S Sidhu Gary D Bader Philip M Kim 《Molecular systems biology》2011,7(1)
Modular protein interaction domains form the building blocks of eukaryotic signaling pathways. Many of them, known as peptide recognition domains, mediate protein interactions by recognizing short, linear amino acid stretches on the surface of their cognate partners with high specificity. Residues in these stretches are usually assumed to contribute independently to binding, which has led to a simplified understanding of protein interactions. Conversely, we observe in large binding peptide data sets that different residue positions display highly significant correlations for many domains in three distinct families (PDZ, SH3 and WW). These correlation patterns reveal a widespread occurrence of multiple binding specificities and give novel structural insights into protein interactions. For example, we predict a new binding mode of PDZ domains and structurally rationalize it for DLG1 PDZ1. We show that multiple specificity more accurately predicts protein interactions and experimentally validate some of the predictions for the human proteins DLG1 and SCRIB. Overall, our results reveal a rich specificity landscape in peptide recognition domains, suggesting new ways of encoding specificity in protein interaction networks. 相似文献
60.
Geetha S Singh V Ram MS Ilavazhagan G Banerjee PK Sawhney RC 《Molecular and cellular biochemistry》2005,278(1-2):101-109
The present study reports the immunomodulatory effects of seabuckthorn (Hippophae rhamnoides L.) leaf extract on cellular and humoral immune response by studying delayed-type hypersensitivity response, IL-2, IL-4 and
γ-IFN levels and antibody titres in chromium-induced immunosuppressed animals. Oral feeding of chromium (30 mg/kg bw) significantly
inhibited antibody production and S-RBC induced delayed-type hypersensitivity response. Administration of leaf extract (100
mg/kg bw) along with chromium significantly inhibited chromium-induced immunosuppression. To understand the immunomodulatory
mechanism of leaf extract, in vitro studies were carried out using rat lymphocytes. Addition of chromium resulted in a significant decrease in lymphocyte size
and increased ROS generation. The leaf extract of seabuckthorn significantly inhibited chromium-induced reactive oxygen species
(ROS) generation and maintained the cell size identical to that of control cells. Chromium treatment markedly inhibited the
mitochondrial transmembrane potential by larger lymphocytes in particular, while the leaf extract restored the same significantly.
Chromium also inhibited significantly concanavalin A (ConA) induced IL-2, IL-4 and γ-IFN production in rat lymphocytes. The
leaf extract (100 μg/ml) alone stimulated IL-2 and γ-IFN production even in the absence of ConA and also inhibited chromium-induced
decline in IL-2 and γ-IFN production but it did not change IL-4 production. These observations suggest that the leaf extract
of seabuckthorn has significant immunomodulatory activity and specifically activates the cell-mediated immune response. (Mol
Cell Biochem 278: 101–109, 2005) 相似文献