Browsing by Subject "molecular analysis"

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    ItemOpen Access
    Activating mutations of STAT5B and STAT3 in lymphomas derived from γδ-T or NK cells
    (Nature Publishing Group, 2015) Küçük, C.; Jiang, B.; Hu X.; Zhang W.; Chan J.K.C.; Xiao W.; Lack, N.; Alkan, C.; Williams J.C.; Avery, K.N.; Kavak P.; Scuto, A.; Sen, E.; Gaulard P.; Staudt L.; Iqbal J.; Zhang W.; Cornish, A.; Gong Q.; Yang Q.; Sun H.; D'Amore F.; Leppä, S.; Liu W.; Fu, K.; De Leval L.; McKeithan, T.; Chan W.C.
    Lymphomas arising from NK or γδ-T cells are very aggressive diseases and little is known regarding their pathogenesis. Here we report frequent activating mutations of STAT3 and STAT5B in NK/T-cell lymphomas (n=51), γδ-T-cell lymphomas (n=43) and their cell lines (n=9) through next generation and/or Sanger sequencing. STAT5B N642H is particularly frequent in all forms of γδ-T-cell lymphomas. STAT3 and STAT5B mutations are associated with increased phosphorylated protein and a growth advantage to transduced cell lines or normal NK cells. Growth-promoting activity of the mutants can be partially inhibited by a JAK1/2 inhibitor. Molecular modelling and surface plasmon resonance measurements of the N642H mutant indicate a marked increase in binding affinity of the phosphotyrosine-Y699 with the mutant histidine. This is associated with the prolonged persistence of the mutant phosphoSTAT5B and marked increase of binding to target sites. Our findings suggest that JAK-STAT pathway inhibition may represent a therapeutic strategy. © 2015 Macmillan Publishers Limited. All rights reserved.
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    Odour intensity learning in fruit flies
    (2009) Yarali, A.; Ehser, S.; Hapil F.Z.; Huang J.; Gerber, B.
    Animals' behaviour towards odours depends on both odour quality and odour intensity. While neuronal coding of odour quality is fairly well studied, how odour intensity is treated by olfactory systems is less clear. Here we study odour intensity processing at the behavioural level, using the fruit fly Drosophila melanogaster. We trained flies by pairing a MEDIUM intensity of an odour with electric shock, and then, at a following test phase, measured flies' conditioned avoidance of either this previously trained MEDIUM intensity or a LOWer or a HIGHer intensity. With respect to 3-octanol, n-amylacetate and 4-methylcyclohexanol, we found that conditioned avoidance is strongest when training and test intensities match, speaking for intensity-specific memories. With respect to a fourth odour, benzaldehyde, on the other hand, we found no such intensity specificity. These results form the basis for further studies of odour intensity processing at the behavioural, neuronal and molecular level. © 2009 The Royal Society.