Association of fibroblast growth factor receptor-1 with c-Src correlates with association between c-Src and cortactin.

The initiation of maximal DNA synthesis by fibroblast growth factor (FGF)-1 requires the presence of the growth factor during the entire G0 to G1 transition period of the cell cycle (Zhan, X., Hu, X., Friesel, R., and Maciag, T. (1993) J. Biol. Chem. 268, 9611-9620). During this time, the phosphorylation of several novel proteins on tyrosine residues occurs, and one of these phosphotyrosyl-containing proteins has been characterized as the murine homolog of the chicken cortactin gene (Zhan, X., Hu, X., Hampton, B., Burgess, W.H., Friesel, R., and Maciag, T. (1993) J. Biol. Chem. 268, 24427-24431), a putative substrate for v-Src. We have examined the possibility that FGF-1 employs c-Src or Src-like kinases as signaling intermediates during the mid and late G1 phase of the NIH 3T3 cell cycle using immunoprecipitation and immunoblot analysis. We have demonstrated that c-Src can associate with cortactin in a FGF-1-dependent manner. We have also demonstrated that a monoclonal antibody prepared against FGF receptor (R)-1 is able to co-precipitate Src-related proteins in lysates from FGF-1-treated NIH 3T3 cells. Furthermore, a kinase-active form of FGFR-1 expressed in a bacterial system was also able to associate with Src kinases in a manner dependent on the phosphorylation status of the FGFR-1 protein. Lastly, the Src homology (SH)-2 domain of v-Src was able to recognize a recombinant form of FGFR-1. Because (i) the association between FGFR-1 and Src-like kinases exhibits kinetics similar to those observed between the Src kinases and cortactin and (ii) the Src-SH2 domain is likely to be involved in the association with FGFR-1, we propose that the association of c-Src with activated FGF receptors may be responsible for the tyrosine phosphorylation of cortactin during the mid to late G1 phase of the cell cycle.

Resistance to antiviral inhibitors caused by the mutation S889A in the highly-conserved 885-GDTDS motif of the herpes simplex virus type 1 DNA polymerase.

Most point substitutions in the highly-conserved 885-GDTDS motif of the HSV-1 DNA polymerase inactivate polymerase elongation activity. However, in an assay system based on expression by in vitro transcription-translation, the mutant GDTDA (S889A) possessed wild-type elongation activity which was highly resistant to phosphonoacetic acid and acyclovir triphosphate, but retained sensitivity to aphidicolin.

[The cochlear implant and phonetics: an analysis of a case with the French implant Chorimac 12]. / Implant cochléaire et phonétique: une analyse de cas avec l'implant français Chorimac 12.

This paper reports on the rehabilitation following implantation of the French cochlear implant, Chorimac 12, in a 66-year-old woman. The electrical stimulation of the device should normally stimulate on a 400-6000 Hz bandwidth. However, tests that had been run after the four-month rehabilitation period indicate that there is no stimulation under 1000 Hz, 2000 Hz seems to be the best bandwidth for stimulation, and over 4000 Hz, almost nothing is audible. An "analytico-global" rehabilitation process has yielded results on vowel, consonant and sentence discrimination: pairs of vowels which offer major contrasts are best discriminated; fricatives are easier to recognize than stops; the longer a sentence is, the easier the patients can identify key words that facilitate identification; also, the more sentences carry phonetic differences, the easier it is to identify them. The results from the analysis of the phonetic material used during the rehabilitation, the new hearing impressions described by the patient and the acoustical measures from acoustic researchers allow us to quantify the restored hearing, define the acquired phonetic code and describe the level of performance reached by the patient.