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Kinoshita, S.

Publications and source records attributed to Kinoshita, S..

3 recordsLinked to original sources

Orthogonal linear separation analysis: an approach to decompose the complex effect of a perturbagen

Drugs have multiple, not single, effects. Decomposition of drug effects into basic components helps us to understand the pharmacological properties of a drug and contributes to drug discovery. We have extended factor analysis and developed a novel profile data analysis method, orthogonal linear separation analysis (OLSA). OLSA contracted 11,911 genes to 118 factors from transcriptome data of MCF7 cells treated with 318 compounds in Connectivity Map. Ontology of the main genes constituting the factors detected significant enrichment of the ontology in 65 of 118 factors and similar results were obtained in two other data sets. One factor discriminated two Hsp90 inhibitors, geldanamycin and radicicol, while clustering analysis could not. Doxorubicin was estimated to inhibit Na+/K+ ATPase, one of the suggested mechanisms of doxorubicin-induced cardiotoxicity. Based on the factor including PI3K/AKT/mTORC1 inhibition activity, 5 compounds were predicted to be novel autophagy inducers, and other analysis including western blotting revealed that 4 of the 5 actually induced autophagy. These findings indicate the potential of OLSA to decompose the effects of a drug and identify its basic components. (<175 words)

bioinformatics

Is reading automatic? Are the ERP correlates of masked priming really lexical?

Humans have an almost unbounded ability to adapt their behaviour to perform different tasks. In the laboratory, this flexibility is sometimes viewed as a nuisance factor that prevents access to the underlying cognitive mechanisms of interest. For example, in order to study \"automatic\" lexical processing, psycholinguists have used masked priming or evoked potentials to measure \"automatic\" lexical processing. However, the pattern of masked priming can be radically altered by changing the task. In lexical decision, priming is observed for words but not for nonwords, yet in a same-different matching task, priming is observed for same responses but not for different responses, regardless of whether the target is a word or a nonword (Norris & Kinoshita, 2008). Here we show that evoked potentials are equally sensitive to the nature of required decision, with the neural activity normally associated with lexical processing being seen for both words and nonwords on same trials, and for neither on different trials. (150)

neuroscience

Designed hybrids facilitate efficient generation of high-resolution linkage maps

In sequencing eukaryotic genomes, linkage maps are indispensable for building scaffolds with which to assemble and/or to validate chromosomes. However, current approaches to construct linkage maps are limited by marker density and cost-effectiveness, especially for wild organisms. We have now devised a new strategy based on artificially generated hybrid organisms to acquire ultra high-density genomic markers at lower cost and build highly accurate linkage maps. Using this method, linkage maps and draft sequences for two species of pufferfish were obtained simultaneously. We anticipate that the method will accelerate genomic analysis of sexually reproducing organisms.

genomics