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“To investigate the frequency of isocitrate dehydrogenase 1 (IDH1) and 2 (IDH2) mutations in pediatric acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL), we sequenced these genes in diagnostic samples from 515 patients BIBW2992 order (227 AMLs and 288 ALLs). Somatic IDH1/IDH2 mutations were rare in ALL (N = 1), but were more common in AML, occurring in 3.5% (IDH1 N-3 and IDH2 N-5), with the frequency higher in AMLs with a normal karyotype (9.8%). The identified IDH1 mutations occurred in codon 132 resulting in replacement of arginine with either cysteine (N = 3) or histidine (N = 1). By contrast, mutations in IDH2 did not
affect the homologous residue but instead altered codon 140, resulting in replacement of arginine with either glutamine (N = 4) or tryptophan (N = 1). Structural modeling of IDH2 suggested
that codon 140 mutations selleck disrupt the enzyme’s ability to bind its substrate isocitrate. Accordingly, recombinant IDH2 R140Q/W were unable to carry out the decarboxylation of isocitrate to a-ketoglutarate (alpha-KG), but instead gained the neomorphic activity to reduce alpha-KG to R(-)-2-hydroxyglutarete (2-HG). Analysis of primary leukemic blasts confirmed high levels of 2-HG in AMLs with IDH1/IDH2 mutations. Interestingly, 3/5 AMLs with IDH2 mutations had FLT3-activating mutations, raising the possibility that these mutations cooperate in leukemogenesis. Leukemia (2011) 25, 1570-1577; doi: 10.1038/leu.2011.133; published online 7 June 2011″
“We investigated brain activity in 3-5-year-old preschoolers as they listened to connected speech stimuli in Japanese (first language), English
(second language), and Chinese (a rarely exposed, foreign language) using near-infrared spectroscopy. Unlike the younger preschoolers who had been exposed to English for almost 1 year, brain activity in the bilateral frontal regions of the older preschoolers who had been exposed to English for almost 2 years was higher for Japanese and English speech stimuli than for Chinese. This tendency seemed to be similar to that observed in adults who had learned English for some years. These results indicate that exposure to a second language affects brain activity to language stimuli among preschoolers. (c) 2012 Elsevier Ireland Ltd and the Japan Methamphetamine Neuroscience Society. All rights reserved.”
“The size of a protein is an important factor for understanding the sequence-structure relationship, and it affects both the amino acid composition and the residue burial of proteins. However, it is usually measured as the number of amino acids, although these effects would result from the reduction of surface regions relative to the volume of core regions in larger proteins. In addition, although these two effects are dependent on each other, they have been studied separately.