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91.
The interaction of acetylcholine receptor and acetylcholinesterase with lipid monolayers was followed by measuring changes in surface pressure.When injected into the subphase of a lipid monolayer, the proteins caused increases in surface pressure from 5 to 10 dynes/cm, indicating a penetration of protein into the monolayer. At pH values below the isoelectric point of the proteins the incorporation was improved. The same was observed when Ca2+ (2 mM) was added.The presence of the enzyme in the mixed film could be demonstrated by using diiso[3H]propyl fluorophosphate-labelled acetylcholinesterase as well as by measuring enzyme activity. Acetylcholine receptor was shown to be present in the mixed film by using a complex made of the receptor and α-[3H]neurotoxin. 相似文献
92.
Hervé Chneiweiss François Hirsch Lluis Montoliu Albrecht M. Müller Solveig Fenet Marion Abecassis Jennifer Merchant Bernard Baertschi Mylène Botbol-Baum James A. Houghton Mihalis Kritikos Janet Mifsud Ewa Bartnik Johannes Rath Christiane Druml Bärbel Friedrich Ana Sofia Carvalho Dirk Lanzerath Agnès Saint-Raymond 《Transgenic research》2017,26(5):709-713
In this consensus paper resulting from a meeting that involved representatives from more than 20 European partners, we recommend the foundation of an expert group (European Steering Committee) to assess the potential benefits and draw-backs of genome editing (off-targets, mosaicisms, etc.), and to design risk matrices and scenarios for a responsible use of this promising technology. In addition, this European steering committee will contribute in promoting an open debate on societal aspects prior to a translation into national and international legislation. 相似文献
93.
The pancreatic stellate cells (PSCs) have complex roles in pancreas, including tissue repair and fibrosis. PSCs surround ATP releasing exocrine cells, but little is known about purinergic receptors and their function in PSCs. Our aim was to resolve whether PSCs express the multifunctional P2X7 receptor and elucidate how it regulates PSC viability. The number of PSCs isolated from wild type (WT) mice was 50% higher than those from the Pfizer P2X7 receptor knock out (KO) mice. The P2X7 receptor protein and mRNA of all known isoforms were expressed in WT PSCs, while KO PSCs only expressed truncated versions of the receptor. In culture, the proliferation rate of the KO PSCs was significantly lower. Inclusion of apyrase reduced the proliferation rate in both WT and KO PSCs, indicating importance of endogenous ATP. Exogenous ATP had a two-sided effect. Proliferation of both WT and KO cells was stimulated with ATP in a concentration-dependent manner with a maximum effect at 100 µM. At high ATP concentration (5 mM), WT PSCs, but not the KO PSCs died. The intracellular Ca2+ signals and proliferation rate induced by micromolar ATP concentrations were inhibited by the allosteric P2X7 receptor inhibitor az10606120. The P2X7 receptor-pore inhibitor A438079 partially prevented cell death induced by millimolar ATP concentrations. This study shows that ATP and P2X7 receptors are important regulators of PSC proliferation and death, and therefore might be potential targets for treatments of pancreatic fibrosis and cancer. 相似文献
94.
Winfried Boos John S. Parkinson Urs Jenal Jörg Vogel Lotte Søgaard‐Andersen 《Molecular microbiology》2013,88(2):219-221
On November 28, 2012 Alexander (Alex) Böhm, a bacterial geneticist, died at age 41, only a few months after taking up a position as an assistant professor at the LOEWE Center for Synthetic Microbiology in Marburg, Germany. Earlier in 2012 Alex had been diagnosed with an aggressive form of thyroid cancer that left him little time to live his scientific and personal dreams. 相似文献
95.
Albrecht Piiper Danuta Stryjek-Kaminska Ralph Gebhardt Stefan Zeuzem 《Journal of cellular physiology》1996,167(1):52-59
Signal transduction of fibroblast growth factor (FGF) receptors is known to involve tyrosine phosphorylation of several substrates, including Grb2, phospholipase C-γ, and phosphatidylinositol 3-kinase, whereas the role of G-proteins in FGF receptor signaling is controversial. In the present study we investigated the role of G-proteins in FGF receptor signaling in rat pancreatic acini. Immunological analysis revealed the presence of FGF receptor and phospholipase C-γ1 in rat pancreatic acini. Both basic fibroblast growth factor (FGF-2) and guanosine 5′-(γ-O-thio)triphosphate (GTPγS) caused an increase in inositol 1,4,5-trisphosphate (1,4,5-IP3) production and amylase release. Combined stimulation of the acini with GTPγS and FGF-2 led to a decrease of these responses as compared to the effect of the single substances. When pancreatic acini were preincubated with FGF-2 (1 nM) or vehicle (water) ADP-ribosylation of the α-subunit of Gi-type G-proteins by pertussis toxin was reduced in membranes prepared from FGF-2 pretreated acini as compared to control acini, suggesting functional interaction of FGF receptors with Gi-proteins. Pretreatment of acini with pertussis toxin which inhibits Gi-type G-proteins abolished the inhibitory effect of GTPγS on FGF-induced 1,4,5-IP3 production and amylase release, whereas the stimulatory effects of FGF-2 and GTPγS on these parameters remained unchanged. In conclusion, these results show communication of FGF receptors and Gi-type G-proteins and that Gi-type G-proteins exert an inhibitory influence on FGF-induced activation of phosphoinositide-specific phospholipase C in pancreatic acinar cells. © 1996 Wiley-Liss, Inc. 相似文献
96.
Bernard Barlaam Sabina Cosulich Martina Fitzek Hervé Germain Stephen Green Lyndsey L. Hanson Craig S. Harris Urs Hancox Kevin Hudson Christine Lambert-van der Brempt Maryannick Lamorlette Françoise Magnien Gilles Ouvry Ken Page Linette Ruston Lara Ward Bénédicte Delouvrié 《Bioorganic & medicinal chemistry letters》2017,27(13):3030-3035
We report the discovery of a novel aminopyrazine series of PI3Kα inhibitors, designed by hybridizing two known scaffolds of PI3K inhibitors. We describe the progress achieved from the first compounds plagued with poor general kinase selectivity to compounds showing high selectivity for PI3Kα over PI3Kβ and excellent general kinase selectivity. This effort culminated with the identification of compound 5 displaying high potency and selectivity, and suitable physiochemical and pharmacokinetic properties for oral administration. In vivo, compound 5 showed good inhibition of tumour growth (86% tumour growth inhibition at 50 mg/kg twice daily orally) in the MCF7 xenograft model in mice. 相似文献
97.
Ole A. Andreassen Rahul S. Desikan Yunpeng Wang Wesley K. Thompson Andrew J. Schork Verena Zuber Nadezhda T. Doncheva Eva Ellinghaus Mario Albrecht Morten Mattingsdal Andre Franke Benedicte A. Lie Ian G. Mills P?l Aukrust Linda K. McEvoy Srdjan Djurovic Tom H. Karlsen Anders M. Dale 《PloS one》2015,10(5)
98.
M. Rosa Pinol Urs Kägi Claus W. Heizmann Brigitte Vogel Jean-Marc Séquier Werner Haas Willi Hunziker 《Journal of neurochemistry》1990,54(6):1827-1833
Many processes in the CNS depend on calcium. The calcium signal is transduced into an intracellular response via Ca2(+)-binding proteins, including calbindin D-28K. In many laboratories, polyclonal antibodies against chicken intestinal calbindin D-28K have been used to study its localization in the brain (normal and degenerated) of various species, including humans, but some of these antisera cross-reacted with other proteins, including calretinin. We purified recombinant rat brain calbindin D-28K to raise antisera in rabbits and purified a recombinant rat-chicken calbindin D-28K hybrid protein to immunize mice for the generation of monoclonal antibodies. These antisera were highly specific for calbindin D-28K, as demonstrated by two-dimensional Western blotting analysis. Immunohistochemical analyses combined with in situ hybridization studies demonstrated that calbindin D-28K in the Purkinje cells of the cerebellum is independent of vitamin D. The antibodies described here will be important tools for studying the regulation of expression of calbindin D-28K and its biological function in the brain and in the PNS. 相似文献
99.
Mabit H Nakano MY Prank U Saam B Döhner K Sodeik B Greber UF 《Journal of virology》2002,76(19):9962-9971
Capsids and the enclosed DNA of adenoviruses, including the species C viruses adenovirus type 2 (Ad2) and Ad5, and herpesviruses, such as herpes simplex virus type 1 (HSV-1), are targeted to the nuclei of epithelial, endothelial, fibroblastic, and neuronal cells. Cytoplasmic transport of fluorophore-tagged Ad2 and immunologically detected HSV-1 capsids required intact microtubules and the microtubule-dependent minus-end-directed motor complex dynein-dynactin. A recent study with epithelial cells suggested that Ad5 was transported to the nucleus and expressed its genes independently of a microtubule network. To clarify the mechanisms by which Ad2 and, as an independent control, HSV-1 were targeted to the nucleus, we treated epithelial cells with nocodazole (NOC) to depolymerize microtubules and measured viral gene expression at different times and multiplicities of infections. Our results indicate that in NOC-treated cells, viral transgene expression was significantly reduced at up to 48 h postinfection (p.i.). A quantitative analysis of subcellular capsid localization indicated that NOC blocked the nuclear targeting of Ad2 and also HSV-1 by more than 90% at up to 7 h p.i. About 10% of the incoming Texas Red-coupled Ad2 (Ad2-TR) was enriched at the nucleus in microtubule-depleted cells at 5 h p.i. This result is consistent with earlier observations that Ad2-TR capsids move randomly in NOC-treated cells at less than 0.1 micro m/s and over distances of less than 5 micro m, characteristic of Brownian motion. We conclude that fluorophore-tagged Ad2 and HSV-1 particles are infectious and that microtubules play a prominent role in efficient nuclear targeting during entry and gene expression of species C Ads and HSV-1. 相似文献
100.
Schwander M Leu M Stumm M Dorchies OM Ruegg UT Schittny J Müller U 《Developmental cell》2003,4(5):673-685
The mechanisms that regulate the formation of multinucleated muscle fibers from mononucleated myoblasts are not well understood. We show here that extracellular matrix (ECM) receptors of the beta1 integrin family regulate myoblast fusion. beta1-deficient myoblasts adhere to each other, but plasma membrane breakdown is defective. The integrin-associated tetraspanin CD9 that regulates cell fusion is no longer expressed at the cell surface of beta1-deficient myoblasts, suggesting that beta1 integrins regulate the formation of a protein complex important for fusion. Subsequent to fusion, beta1 integrins are required for the assembly of sarcomeres. Other ECM receptors such as the dystrophin glycoprotein complex are still expressed but cannot compensate for the loss of beta1 integrins, providing evidence that different ECM receptors have nonredundant functions in skeletal muscle fibers. 相似文献