In order to separate the cognitive processes associated with phonological encoding and the use of a visual word form lexicon in reading, it is desirable to compare the processing of words presented in a visually familiar form with words in a visually unfamiliar form. Japanese Kana orthography offers this possibility. Two phonologically equivalent but visually dissimilar syllabaries allow the writing of, for example, foreign loanwords in two ways, only one of which is visually familiar. Familiarly written words, unfamiliarly written words, and pseudowords were presented in both Kana syllabaries (yielding six conditions in total) to participants during an fMRI measurement with a silent articulation task (Experiment 1) and a phonological lexical decision task (Experiment 2) using an event-related design. Consistent over two experimental tasks, the three different stimulus types (familiar, unfamiliar, and pseudoword) were found to activate selectively different brain regions previously associated with phonological encoding and word retrieval or meaning. Compatible with the predictions of the dual-route model for reading, pseudowords and visually unfamiliar words, which have to be read using phonological assembly, caused an increase in brain activity in left inferior frontal regions (BA 44/47), as compared to visually familiar words. Visually familiar and unfamiliar words were found to activate a range of areas associated with lexico-semantic processing more strongly than pseudowords, such as the left and right temporo-parietal region (BA 39/40), a region in the left middle/inferior temporal gyrus (BA 20/21), and the posterior cingulate (BA 31).
Although the action of insulin-like growth factor-I (IGF-I) on bone formation has been extensively investigated, the effect of the factor on bone resorption is little known. We first examined the effect of IGF-I on bone resorption by preexistent osteoclasts by using unfractionated bone cells cultured on dentin slices. IGF-I had a dose-related effect of stimulating bone resorption by preexistent osteoclasts, whereas IGF-II did not. When IGF-I was added to cultures of bone cells after preexistent osteoclasts had degenerated on the dentin slices, IGF-I increased the number of osteoclastic multinucleate cells (MNCs) with tartrate-resistant acid phosphatase activity. Moreover, IGF-I augmented the area of pits produced by newly formed osteoclasts. These results suggest that IGF-I directly or indirectly stimulates osteoclast recruitment and activation. Therefore, we next examined the direct effect of IGF-I on osteoclastic MNC formation by using hemopoietic blast cells. In the presence of 1,25-dihydroxyvitamin D3, IGF-I, like granulocyte-macrophage colony-stimulating factor (GM-CSF), dose-dependently increased the number of TRAP-positive MNCs. This stimulatory effect of IGF-I was additive with that of GM-CSF. Both IGF-I and GM-CSF supported the survival of the blast cells, indicating that IGF-I as well as GM-CSF are supporting factors for osteoclast differentiation. In addition, the blast cells possessed high affinity binding sites for IGF-I, with a Kd of 0.8 nM. These data, thus, indicate that IGF-I stimulates osteoclastic bone resorption through its direct or indirect action of supporting the generation and activation of osteoclasts.
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