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31.
Ludovica Riera Elena Lasorsa Chiara Ambrogio Nadia Surrenti Claudia Voena Roberto Chiarle 《The Journal of biological chemistry》2010,285(34):26441-26450
Most anaplastic large cell lymphomas (ALCL) express oncogenic fusion proteins derived from chromosomal translocations or inversions of the anaplastic lymphoma kinase (ALK) gene. Frequently ALCL carry the t(2;5) translocation, which fuses the ALK gene to the nucleophosmin (NPM1) gene. The transforming activity mediated by NPM-ALK fusion induces different pathways that control proliferation and survival of lymphoma cells. Grb2 is an adaptor protein thought to play an important role in ALK-mediated transformation, but its interaction with NPM-ALK, as well as its function in regulating ALCL signaling pathways and cell growth, has never been elucidated. Here we show that active NPM-ALK, but not a kinase-dead mutant, bound and induced Grb2 phosphorylation in tyrosine 160. An intact SH3 domain at the C terminus of Grb2 was required for Tyr160 phosphorylation. Furthermore, Grb2 did not bind to a single region but rather to different regions of NPM-ALK, mainly Tyr152–156, Tyr567, and a proline-rich region, Pro415–417. Finally, shRNA knockdown experiments showed that Grb2 regulates primarily the NPM-ALK-mediated phosphorylation of SHP2 and plays a key role in ALCL cell growth. 相似文献
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ESCs Require PRC2 to Direct the Successful Reprogramming of Differentiated Cells toward Pluripotency
Carlos F. Pereira Francesco M. Piccolo Tomomi Tsubouchi Stephan Sauer Natalie K. Ryan Ludovica Bruno David Landeira Joana Santos Ana Banito Jesus Gil Haruhiko Koseki Matthias Merkenschlager Amanda G. Fisher 《Cell Stem Cell》2010,6(6):547-556
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34.
Segat L Bevilacqua D Boniotto M Arraes LC de Souza PR de Lima Filho JL Crovella S 《Immunogenetics》2006,58(5-6):471-473
In our study, we identified a polymorphism (C-607A) in the promoter region of the IL-18 gene that shows different frequencies between human immunodeficiency virus (HIV)-1-infected children and healthy controls in a pediatric Brazilian population. The presence of the −607 C allele correlates to HIV-1 infection and confers an increased risk of infection in subjects carrying the single nucleotide polymorphism. 相似文献
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Montanucci L Laayouni H Dall'Olio GM Bertranpetit J 《Molecular biology and evolution》2011,28(1):813-823
N-glycosylation is one of the most important forms of protein modification, serving key biological functions in multicellular organisms. N-glycans at the cell surface mediate the interaction between cells and the surrounding matrix and may act as pathogen receptors, making the genes responsible for their synthesis good candidates to show signatures of adaptation to different pathogen environments. Here, we study the forces that shaped the evolution of the genes involved in the synthesis of the N-glycans during the divergence of primates within the framework of their functional network. We have found that, despite their function of producing glycan repertoires capable of evading rapidly evolving pathogens, genes involved in the synthesis of the glycans are highly conserved, and no signals of positive selection have been detected within the time of divergence of primates. This suggests strong functional constraints as the main force driving their evolution. We studied the strength of the purifying selection acting on the genes in relation to the network structure considering the position of each gene along the pathway, its connectivity, and the rates of evolution in neighboring genes. We found a strong and highly significant negative correlation between the strength of purifying selection and the connectivity of each gene, indicating that genes encoding for highly connected enzymes evolve slower and thus are subject to stronger selective constraints. This result confirms that network topology does shape the evolution of the genes and that the connectivity within metabolic pathways and networks plays a major role in constraining evolutionary rates. 相似文献
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Alessandro Musenga Mario Amore Roberto Mandrioli Ernst Kenndler Ludovica de Martino Maria Augusta Raggi 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2009,877(11-12):1126-1132
A method based on capillary electrophoresis has been developed for the analysis of the novel antidepressant drug duloxetine in human plasma. The method makes use of laser-induced fluorescence detection after derivatisation of the analyte with 5-(4,6-dichlorotriazinyl)aminofluorescein at pH 11. A single step liquid/liquid extraction procedure with a mixture of hexane/2-propanol allows the sample clean-up with extraction yields always ≥84% and interference removal. The electrophoretic separation is achieved using uncoated fused silica capillaries (60.0 cm effective length, 75.0 cm total length, 50 μm internal diameter) and a background electrolyte composed of borate buffer (40 mM, pH 10.3), tetrabutylammonium bromide (10 mM), and acetone (10%, v/v). The applied voltage is 20 kV; the samples are injected by pressure (50 mbar × 8 s). The method has been fully validated in terms of linearity range (2.5–150 ng mL?1), LOD and LOQ (1.0 and 2.5 ng mL?1, respectively), precision (R.S.D. < 6.7%) and accuracy (recovery >78%). Application to samples obtained from patients under treatment with duloxetine gave good results. The method represents the first application of capillary electrophoresis to the analysis of duloxetine in human plasma. 相似文献
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Ludovica Morera Geoffray Labar Giorgio Ortar Didier M. Lambert 《Bioorganic & medicinal chemistry》2012,20(21):6260-6275
A series of (1H-benzo[d][1,2,3]triazol-1-yl)(4-benzylpiperazin-1-yl)methanones and of (1H-benzo[d][1,2,3]triazol-1-yl)(4-phenylpiperazin-1-yl)methanones has been prepared and tested on human fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL). In the benzylpiperazinyl series, compound 29 (ML30) exhibited an IC50 value of 0.54 nM on MAGL, combined with a 1000-fold selectivity versus FAAH, while compounds 11 and 16 acted as potent dual FAAH-MAGL inhibitors (IC50 <10 nM). In the phenylpiperazinyl series, compounds 37, 38, 42, and 43 displayed IC50 values against MAGL in the nanomolar range, whilst being between one and two orders of magnitude less potent on the FAAH, while compounds 31 and 32 were potent FAAH inhibitors (IC50 <20 nM) and over 12-fold selective versus MAGL. The key structural determinants driving the structure–activity relationships were explored by the minimization of the inhibitors inside the active site of both enzymes. 相似文献
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Capozzi O Purgato S Verdun di Cantogno L Grosso E Ciccone R Zuffardi O Della Valle G Rocchi M 《Chromosoma》2008,117(4):339-344
It has been hypothesized that human clinical neocentromeres and evolutionary novel centromeres (ENC) represent two faces of the same phenomenon. However, there are only two reports of loci harboring both a novel centromere and a clinical neocentromere. We suggest that only the tip of the iceberg has been scratched because most neocentromerization events have a very low chance of being observed. In support of this view, we report here on a neocentromere at 9q33.1 that emerged in a ring chromosome of about 12 Mb. The ring was produced by a balanced rearrangement that was fortuitously discovered because of its malsegregation in the propositus. Chromatin-immunoprecipitation-on-chip experiments using anti-centromere protein (CENP)-A and anti-CENP-C antibodies strongly indicated that a novel centromeric domain was present in the ring, in a chromosomal domain where an ENC emerged in the ancestor to Old World monkeys. 相似文献