Performance of children with typical development when reading and interpreting graphic-symbol sequences.

In order to understand a sequence of graphic symbols as sentences, one must not only recognize the meaning of individual symbols but also integrate their meaning together. In this study children without disabilities were asked to perform two tasks that presented sequences of graphics as stimuli but that differed in the need to treat the symbols as a sentence (i.e., with evidence of relationships among the individual symbols): a "reading" task (transpose the symbol sequence into speech), and an act-out task (demonstrate the meaning of the symbol sequences using puppets). The participants, aged 3 (n=18), 4 (n=36), 5 (n=27), and 6 (n=23) years, all succeeded on the reading task, but the younger groups were much less successful than the older groups on the act-out task. The children were more likely to pass the act-out task if they used conjugated rather than infinitive verb forms in their spoken responses on the reading task. In the younger age groups, children who used conjugated verb forms had higher receptive vocabulary scores. The findings suggest that being able to reproduce a sequence of symbols does not guarantee that the symbols are treated as a sentence. The inclusion in the study of children who were able to respond using speech, permitted observation of two types of responses (conjugated versus infinitive verb forms) that revealed different levels of understanding of graphic symbol sequences.

Ocsyn and mitochondrial-canalicular complexes in vestibular hair cells.

Ocsyn, a syntaxin-interacting protein characterized by Safieddine et al. [Safieddine, S., Ly, C.D., Wang, Y.-X., Kachar, B., Petralia, R.S., Wenthold, R.J., 2002. Ocsyn, a novel syntaxin-interacting protein enriched in the subapical region of inner hair cells. Mol. Cell. Neurosci., 20, 343-353] in the guinea pig organ of Corti was primarily identified in organelles located at the subapical region of inner hair cells. They proposed that in cochlear inner hair cells, ocsyn was involved in protein trafficking associated to recycling endosomes. Ocsyn happens to be highly homologous to syntabulin with an almost identical syntaxin-binding domain. Syntabulin is believed to attach syntaxin-containing vesicles to kinesin for their axonal transport along microtubules. The present study shows the distribution of ocsyn in guinea pig and rat vestibular hair cells using immunocytochemistry and confocal microscopy. Ocsyn was characterized by intense immunolabeled spots distributed exclusively in type I and II vestibular hair cells. The subcuticular region under the cuticular plate exhibited particularly densely packed spots. In the neck region of the sensory cells, where microtubules are abundant, there was no colocalization of ocsyn and alpha-tubulin. Ocsyn labeled spots were also present in the medial and basal hair cell regions, particularly in the supranuclear and infranuclear regions. Mitochondria are particularly numerous in these three regions (subcuticular, supranuclear and infranuclear). Double labeling of ocsyn and cytochrome c showed that ocsyn was present in the same zones that mitochondria. This, together with the great similarity of ocsyn and syntabulin, suggest that, akin to syntabulin, ocsyn is involved in addressing organelles. We propose that ocsyn is involved in the formation of the canalicular-mitochondrial complexes depicted by Spicer et al. [Spicer, S.S., Thomopoulos, G.N., Schulte, B.A., 1999. Novel membranous structures in apical and basal compartments of inner hear cells. J. Comp. Neurol., 409, 424-437].

Overproduction of BCR-ABL induces apoptosis in imatinib mesylate-resistant cell lines.

BACKGROUND: Imatinib mesylate, a BCR-ABL tyrosine kinase inhibitor, induces apoptosis in chronic myeloid leukemia cells. Resistance to imatinib is currently the most important concern of this treatment. One of the main mechanisms of this resistance is overexpression of BCR-ABL. METHODS: In the current study, the authors investigated the correlation between BCR-ABL overexpression and apoptosis in BaF/BCR-ABL and LAMA84 cell lines resistant to imatinib suddenly deprived of the inhibitor, and compared with their sensitive counterpart. RESULTS: Removal of imatinib from culture medium led to a decrease in Bcr-Abl protein expression by Day 5, which was sustained for > or = 3 weeks of imatinib deprivation. Apoptosis was observed after 3 days of imatinib deprivation in resistant lines accompanied by caspase activation, loss of membrane asymmetry (annexin V staining), and alteration of mitochondrial potential (dihexyloxacarbocyanine iodide [DiOC6]). Transient activation of the STAT5/Bcl-xL pathway and Akt kinase activity preceded these responses. CONCLUSIONS: Thus, imatinib removal led to apoptosis of BCR-ABL-overexpressing leukemic cells, a phenomenon that could be exploited to sensitize imatinib-resistant cells to the cytotoxic effect of other drugs.