Interaction of hnRNP A1 with telomere DNA G-quadruplex structures studied at the single molecule level.

G-rich telomeric DNA sequences can form G-quadruplex structures. The heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) and a shortened derivative (UP1) are active in telomere length regulation, and it has been reported that UP1 can unwind G-quadruplex structures. Here, we investigate the interaction of hnRNP A1 with G-quadruplex DNA structures containing the human telomere repeat (TTAGGG) by gel retardation assays, ensemble fluorescence energy transfer (FRET) spectroscopy, and single molecule FRET microscopy. Our biochemical experiments show that hnRNP A1 binds well to the G-quadruplex telomeric DNA. Ensemble and single molecule FRET measurements provide further insight into molecular conformation: the telomeric DNA overhang is found to be in a folded state in the absence of hnRNP A1 and to remain predominantly in a compact state when complexed with hnRNP A1. This finding is in contrast to the previously reported crystal structures of UP1-telomere DNA complexes where the DNA oligo within the protein-DNA complex is in a fully open conformation.

Joint attention on actions: acquiring verbs in ostensive and non-ostensive contexts.

Two studies of verb learning are reported. The focus of both studies was on children in their second year of life learning verbs in various pragmatic contexts. Of particular interest was the comparison of ostensive contexts--in which word and referent were simultaneously present in the child's perceptual field--to non-ostensive contexts. In a naturalistic study of 24 children at 1;3 and 1;9, it was found that mothers modelled verbs for their children most often BEFORE the referent action actually occurred. Over 60% of maternal verbs were used to refer to actions that mothers wished children to perform or that they were anticipating their performing (IMPENDING actions). Some verbs were also used to refer to current actions (ONGOING actions) or actions that had just been completed (COMPLETED actions). Children responded with comprehension most often to impending models. Impending and completed models, but not ongoing models, were correlated with children's verb vocabularies at 1;9. The second study was a lexical training study of 48 two-year-olds. Children learned to produce a novel verb best when it was modelled in the impending condition. They learned to comprehend it equally well in the impending and completed conditions. Children showed no signs of superior learning in the ostensive (ongoing) learning context. Results of the two studies are discussed in terms of the different learning processes involved in acquiring nouns and verbs, and, more broadly, in terms of a social-pragmatic view of language acquisition in which the ostensive teaching paradigm is but one of many contexts in which children learn to establish a joint attentional focus with mature language users.

Imitative learning of actions on objects by children, chimpanzees, and enculturated chimpanzees.

In this study we compared the abilities of chimpanzees and human children to imitatively learn novel actions on objects. Of particular interest were possible differences between chimpanzees raised mostly with conspecifics (mother-reared) and chimpanzees raised in a human-like cultural environment (enculturated). Subjects were thus 3 enculturated and 3 mother-reared chimpanzees, along with 8 18-month-old and 8 30-month-old human children. Each subject was tested over a 2-day period with 16 novel objects. The introduction of each object was preceded by a baseline period in which the subject's natural proclivities toward the object were determined. For 12 objects, a human experimenter demonstrated first a simple and then a complex novel action, instructing the subject in each case to "Do what I do" (chimpanzees were prepared for the task behaviorally as well). For the other 4 objects, demonstration of a single action took place on the first day and the subject's opportunity to imitate was delayed until the second day, 48 hours later. Actions that a subject produced in baseline were excluded from further analysis. For each analyzed action, the subject's behavior was scored as to whether it successfully reproduced (1) the end result of the demonstrated action, and (2) the behavioral means used by the demonstrator. Results showed that in immediate imitation the mother-reared chimpanzees were much poorer imitators than the enculturated chimpanzees and the human children, who did not differ from one another. Surprisingly, on the delay trials, the enculturated chimpanzees significantly outperformed the other 3 groups. We conclude from these results that a human-like sociocultural environment is an essential component in the development of human-like social-cognitive and imitative learning skills for chimpanzees, and perhaps for human beings as well.