Identification of six novel autophosphorylation sites on fibroblast growth factor receptor 1 and elucidation of their importance in receptor activation and signal transduction

Fibroblast growth factor receptor (FGFR) activation leads to receptor autophosphorylation and increased tyrosine phosphorylation of several intra cellular proteins. We have previously shown that autophosphorylated tyrosine 766 in FGFR1 serves as a binding site for one of the SH2 domains of phospholipase Cy and couples FGFR1 to phosphatidylinositol hydrolysis in several cell types. In this report, we describe the identification of six additional autophosphorylation sites (Y-463, Y-583, Y-585, Y-653, Y-654 and Y-730) on FGFR1. We demonstrate that autophosphorylation on tyrosines 653 and 654 is important for activation of tyrosine kinase activity of FGFR1 and is therefore essential for FGFR1-mediated biological responses. In contrast, autophosphorylation of the remaining four tyrosines is dispensable for FGFR1-mediated mitogen-activated protein kinase activation and mitogenic signaling in L-6 cells as well as neuronal differentiation of PC12 cells. Interestingly, both the wild-type and a mutant FGFR1 (FGFR1-4F) are able to phosphorylate Shc and an unidentified Grb2-associated phosphoprotein of 90 kDa (pp90). Binding of the Grb2/Sos complex to phosphorylated Shc and pp90 may therefore be the key link between FGFR1 and the Ras signaling pathway, mito-genesis, and neuronal differentiation.     

Social reforms and the future of school practice: Implications for American psychology.

Social reforms in American education are setting the stage for a paradigm shift in our nation's schools. The convergence of education and health care reform and the movement in the human services arena toward service integration models provide an unprecedented opportunity to redefine psychological services related to schools for the next century. Whereas school psychological services historically have been linked to changes in special education legislation, social reforms in education and health care that emphasize educational achievement and whole-child development offer promise for expanding and enhancing the roles of psychologists whose practices relate to schools and children. This article explores the foundations for change and highlights critical areas in which psychological practice in the schools may develop in the 1990s and beyond. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The regulation of drugs and medicines in horse racing in the United States. The Association of Racing Commissioners International Uniform Classification of Foreign Substances Guidelines

It is proposed that both polar and radical reactions should be considered when discussing radical ion reactivity. The fact that only the polar reactivity has dominated previous discussions is pointed out. It is argued that if the configuration mixing model is applicable for the estimation of radical cation-nucleophile (or cation-nucleophile) combination reaction barriers, the theory should also explain the reactivity of the proton toward anionic nucleophiles. The model severely overestimates reaction barriers for the latter reactions. The discussion is centered around the following hypothesis: In the absence of severe steric effects, the reactivity of radical ions, especially evident in the reactions with radicals (for example very few radical cations react with dioxygen at measurable rates), is dominated by the degree of coupling between charge and radical centers. Evidence from the literature supporting the hypothesis is presented for a number of different classes of radical ion reactions. Further work to test the validity of the hypothesis is proposed for many of the reaction types. Triarylmethyl radicals and carbenium ions are suggested as models to which the radical and polar reactivities of 9,10-diarylanthracene radical cations may be compared. It is concluded that the radical cation/carbenium ion comparison (for the reaction with acetate ion) would show similar reactivities while the radical cation/free radical comparison (for the reaction with dioxygen) would fail, since no reaction at all would be observed with the radical cation while the free radical reacts rapidly.     

The frequency of disfluencies during phonatory transitions in stuttered and nonstuttered speech

The AA. investigated the frequency of antibodies against Toxoplasma gondii in 426 women with repeated abortions, perinatal mortality and malformed newborns. They showed on the whole a low incidence even if they demonstrated a high incidence (77.7%) of antibodies in women with malformed newborns. The meaning of the observations are briefly discussed.     

Pharmacokinetics and metabolic disposition of 14C-metronidazole-derived radioactivity in rat after intravenous and intravaginal administration

Urinary metabolites and the pharmacokinetics of radioactivity derived from 14C-metronidazole (14C-MTZ) were determined after intravenous (iv) or intravaginal (ivg) administration of 10 mg/kg to adult rats. Following iv or ivg administration, the disappearance of 14C from blood followed the kinetics of a two-compartment open-system model. The blood half-lives of 14C during the beta-phase were 10.9 +/- 1.6 and 13.6 +/- 4.2 hr, after iv and ivg administration, respectively. After ivg application, the MTZ-derived radioactivity was detected in tail blood at 5 min, peaked at 1 hr, declined rapidly to 6 hr and more slowly thereafter. The vaginal absorption half-life of 14C-MTZ was 0.28 +/- 0.09 hr. About 12% of the administered dose remained in the vagina after 1 hr and 1.5% after 24 hr. At 24 hr, the tissue distribution and concentration of 14C were similar in iv and ivg dosed rats, the highest 14C concentration being present in the kidneys and lowest in the fat. The percentages of the dose excreted in 24 hr in the urine and feces were 58 and 15 after iv administration, compared to 37 and 40 after the ivg route, respectively. Unchanged 14C-MTZ and five of its metabolites were detected in the urine irrespective of the route of administration. The results show that metronidazole is rapidly absorbed through the vaginal mucosa of the rat and the metabolism and excretion of this chemotherapeutic agent are influenced by the route of administration.