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61.
The inhibitory effect of calmodulin on the assembly of mature and immature rat brain microtubules was compared with that of the two major structural domains of this protein, the COOH-terminal fragment (amino acids 78-148) and the NH2-terminal fragment (amino acids 1-77), to determine the calmodulin structural domain responsible for the inhibitory effect on microtubule assembly. Microtubules prepared during the early stages of brain development, i.e., during intensive neurite outgrowth, are more sensitive to inhibition by the Ca2(+)-calmodulin complex than those obtained from adult brain. Significant inhibition of immature microtubule assembly was observed with both fragments in the absence of Ca2+, but the effects were more important when Ca2+ was present. With adult brain microtubules, the two fragments remained without effect on assembly in the absence of Ca2+, whereas some inhibition was seen in its presence but only with the COOH-terminal polypeptide. Under all these conditions, the COOH-terminal fragment was always more active than the NH2-terminal fragment on microtubule polymerization, albeit to a lesser extent than native calmodulin. 相似文献
62.
N. Jacobs Roland Greimers Alessandra Mazzoni Mohamed Trebak Nicole Schaaf-Lafontaine Jacques Boniver Michel P. Moutschen 《Cancer immunology, immunotherapy : CII》1996,42(6):369-375
In this study we have specifically investigated the participation of T cells in the cytotoxic activity of peripheral blood
lymphocytes (PBL) activated by interleukin-2 (IL-2, 50 U/ml) alone or in combination with an anti-CD3 mAb (BMA030, 10 ng/ml,
IgG2a). Purified CD3+ T cells, incubated in the presence of the anti-CD3 mAb for 4 days, mediated a cytotoxic activity against HL60 and U937 tumor
cell lines. Several findings suggested the involvement of a redirected-cytotoxicity phenomenon, since the lytic process was
restricted to target cell lines bearing the high-affinity Fcγ receptor (FcγRI) and T lymphocytes stimulated by IL-2 alone
did not lyse these cell lines. Furthermore, anti-CD3 mAb F(ab′)2, anti-CD3 IgG1 (UCHT1), phytohemagglutinin or staphylococcal enterotoxin A did not induce a similar cytotoxic activity in
T lymphocytes. The cytotoxic process occurred in the presence of a very low level of anti-CD3 antibodies (in the nanomolar
range). The cytotoxic activity of T cells stimulated by IL-2 or by IL-2 + BMA030, against OVCAR-3 cells (MOv18+ ovarian tumor cell line), was also compared in the presence of a bispecific antibody (OC/TR, anti-CD3 × MOv18). The stimulation
by IL-2 + BMA030 induced approximately a twofold higher cytotoxic activity than IL-2-activated T cells. This could be related
to the state of activation of effector cells stimulated by IL-2 + BMA030, since the phenotypic analysis showed an increased
proportion of T cells expressing several activation/differentiation markers (CD25, HLA-DR, CD45R0, adhesion molecules). These
findings could be applied to the design of therapeutic protocols using anti-CD3 ×antitumoral bispecific antibodies.
Received: 6 December 1995 / Accepted: 4 June 1996 相似文献
63.
Rolf Frischknecht Christian Bauer Christof Bucher Linda Ager-Wick Ellingsen Lukas Gutzwiller Britta Heimbach René Itten Xun Liao Evangelos Panos Stephan Pfister Tobias Schmidt Valentin Stahel Philippe Stolz Peter Toggweiler Karin Treyer Jacques Villeneuve Andreas Wade Marcel Weil 《The International Journal of Life Cycle Assessment》2018,23(8):1716-1721
64.
Danny Burg Dmitri V Filippov Ralph Hermanns Gijs A van der Marel Jacques H van Boom Gerard J Mulder 《Bioorganic & medicinal chemistry》2002,10(1):195-205
Elevated levels of glutathione-S-transferase (GST) isoenzymes are found in many tumor cells and are thought to play a role in the onset of multidrug resistance (MDR). To evaluate the contribution of GST to this process, inhibitors are needed. Glutathione (GSH) conjugates, although good GST inhibitors, cannot be used in vivo, because they are eliminated rapidly. In this paper, we describe the synthesis of a series of novel peptidomimetic glutathione analogues that are stabilized against peptidase mediated breakdown. The peptide bonds in GSH were replaced by isosteres, such as the 'reduced' amide (which was prepared using a novel method), N-methylamide, urethane, and methylene linkages. The in vitro evaluation of the compounds focuses on GST inhibition and stability towards gamma-glutamyl-transpeptidase (gammaGT), the main enzyme involved in GSH breakdown. The compounds were conjugated to the model electrophile ethacrynic acid (EA) to resemble GS-EA, an efficient GST inhibitor. All novel GSH-analogues were shown to inhibit rat liver cytosolic GSTs. Furthermore, peptidomimetic changes of the gamma-glutamyl-cysteine amide bond greatly improved stability towards gammaGT. These compounds may therefore be useful in the design of novel in vivo applicable GST inhibitors. 相似文献
65.
Culture conditions differentially affect the translation of individual Escherichia coli mRNAs. 总被引:4,自引:0,他引:4
Our aim is to investigate whether changes in growth conditions can differentially affect the initiation of translation from individual Escherichia coli mRNAs that are not subjected to specific translational control. As a model system, we have constructed a series of point-mutated lacZ genes which differ in their Shine-Dalgarno (SD) sequence, their initiator codon, or the secondary structure around these elements. Alterations in growth conditions produced large (up to 8-fold) changes in the relative expression from these genes, which, we argue, stem from changes in their relative efficiencies of translation initiation. In particular, compared to genes bearing mutations outside the SD or initiator codon, genes mutated in these elements experience a significant decrease in their expression when cells are grown in minimal rather than rich medium; at 42 degrees C rather than 37 degrees C; or under amino acid starvation. We discuss the mechanisms underlying these effects, and evocate their possible generality. 相似文献
66.
Claudia Demarta‐Gatsi Anna Rivkin Vincenzo Di Bartolo Roger Peronet Shuai Ding Pierre‐Henri Commere Franois Guillonneau Jacques Bellalou Sbastien Brûl Paula Abou Karam Sidney R. Cohen Thibault Lagache Chris J. Janse Neta Regev‐Rudzki Salaheddine Mcheri 《Cellular microbiology》2019,21(7)
Protozoan pathogens secrete nanosized particles called extracellular vesicles (EVs) to facilitate their survival and chronic infection. Here, we show the inhibition by Plasmodium berghei NK65 blood stage‐derived EVs of the proliferative response of CD4+ T cells in response to antigen presentation. Importantly, these results were confirmed in vivo by the capacity of EVs to diminish the ovalbumin‐specific delayed type hypersensitivity response. We identified two proteins associated with EVs, the histamine releasing factor (HRF) and the elongation factor 1α (EF‐1α) that were found to have immunosuppressive activities. Interestingly, in contrast to WT parasites, EVs from genetically HRF‐ and EF‐1α‐deficient parasites failed to inhibit T cell responses in vitro and in vivo. At the level of T cells, we demonstrated that EVs from WT parasites dephosphorylate key molecules (PLCγ1, Akt, and ERK) of the T cell receptor signalling cascade. Remarkably, immunisation with EF‐1α alone or in combination with HRF conferred a long‐lasting antiparasite protection and immune memory. In conclusion, we identified a new mechanism by which P. berghei‐derived EVs exert their immunosuppressive functions by altering T cell responses. The identification of two highly conserved immune suppressive factors offers new conceptual strategies to overcome EV‐mediated immune suppression in malaria‐infected individuals. 相似文献
67.
68.
Valérian Meline Wesley Delage Chrystelle Brin Camille Li-Marchetti Daniel Sochard Matthieu Arlat Céline Rousseau Armelle Darrasse Martial Briand Guillaume Lebreton Perrine Portier Marion Fischer-Le Saux Karine Durand Marie-Agnès Jacques Etienne Belin Tristan Boureau 《Molecular Plant Pathology》2019,20(1):33-50
Cases of emergence of novel plant-pathogenic strains are regularly reported that reduce the yields of crops and trees. However, the molecular mechanisms underlying such emergence are still poorly understood. The acquisition by environmental non-pathogenic strains of novel virulence genes by horizontal gene transfer has been suggested as a driver for the emergence of novel pathogenic strains. In this study, we tested such an hypothesis by transferring a plasmid encoding the type 3 secretion system (T3SS) and four associated type 3 secreted proteins (T3SPs) to the non-pathogenic strains of Xanthomonas CFBP 7698 and CFBP 7700, which lack genes encoding T3SS and any previously known T3SPs. The resulting strains were phenotyped on Nicotiana benthamiana using chlorophyll fluorescence imaging and image analysis. Wild-type, non-pathogenic strains induced a hypersensitive response (HR)-like necrosis, whereas strains complemented with T3SS and T3SPs suppressed this response. Such suppression depends on a functional T3SS. Amongst the T3SPs encoded on the plasmid, Hpa2, Hpa1 and, to a lesser extent, XopF1 collectively participate in suppression. Monitoring of the population sizes in planta showed that the sole acquisition of a functional T3SS by non-pathogenic strains impairs growth inside leaf tissues. These results provide functional evidence that the acquisition via horizontal gene transfer of a T3SS and four T3SPs by environmental non-pathogenic strains is not sufficient to make strains pathogenic. In the absence of a canonical effector, the sole acquisition of a T3SS seems to be counter-selective, and further acquisition of type 3 effectors is probably needed to allow the emergence of novel pathogenic strains. 相似文献
69.
70.
Momath Lo Abdou K.D. Diaw Diariatou Gningue‐Sall Mehmet A. Oturan Mohamed M. Chehimi Jean‐Jacques Aaron 《Luminescence》2019,34(5):489-499
To develop conducting organic polymers (COPs) as luminescent sensors for determination of toxic heavy metals, a new benzene sulfonic acid‐doped polypyrrole (PPy‐BSA) thin film was electrochemically prepared by cyclic voltammetry (CV) on flexible indium tin oxide (ITO) electrode in aqueous solution. PPy‐BSA film was characterized by FTIR spectrometry, X‐ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM). The optical properties of PPy‐BSA were investigated by ultraviolet (UV)‐visible absorption and fluorescence spectrometry in dimethylsulfoxide (DMSO) diluted solutions. PPy‐BSA fluorescence spectra were strongly quenched upon increasing copper(II) ion (Cu2+) and lead(II) ion (Pb2+) concentrations in aqueous medium, and linear Stern–Volmer relationships were obtained, which indicated the existence of a main dynamic fluorescence quenching mechanism. BSA‐PPy sensor showed a high sensitivity for detection of both metallic ions, Cu2+ and Pb2+, with very low limit of detection values of 3.1 and 18.0 nM, respectively. The proposed quenching‐fluorimetric sensor might be applied to the determination of traces of toxic heavy metallic ions in water samples. 相似文献