Lexical and conceptual representation in beginning and proficient bilinguals

Two hypotheses about the association between the equivalent words in a bilingual's two languages are considered. The word association hypothesis proposes that a direct association is established between words in the two languages. During second-language acquisition, that association is used to understand and produce words in the second language by retrieving a word in the first language. The concept mediation hypothesis proposes that the only connection between the two languages is via an underlying, amodal conceptual system, one to which pictured objects also have access. The hypotheses make different predictions about the time to name pictures in the second language relative to the time to translate first-language words into the second language. Two experiments are reported, one with proficient Chinese-English bilinguals and the second with nonfluent English-French bilinguals (American high school students). Subjects read words aloud, named pictures, and translated words; one Chinese-English group categorized pictures and words. The results were consistent with the concept mediation hypothesis and contradicted predictions of the word association hypothesis. There was no evidence for a direct association between words in the two languages in either bilingual group. © 1984 Academic Press, Inc.link_to_subscribed_fulltex

Chemical synthesis of the novel Ca2+ messenger NAADP.

The first total chemical synthesis of nicotinamide adenine dinucleotide phosphate (beta-NADP, 2) as a single isomer was achieved. This was subsequently converted into the important second messenger nicotinic acid adenine dinucleotide phosphate (p-NAADP) 1 and the identity of this material confirmed by biological evaluation. This flexible synthetic route offers new opportunities for the generation of NAADP 1 analogues that cannot be generated directly from NADP 2 or mainly enzymatic methods

Chemical synthesis of the second messenger nicotinic acid adenine dinucleotide phosphate by total synthesis of nicotinamide adenine dinucleotide phosphate.

Signaling dinucleotides: The first single-isomer synthesis of nicotinamide adenine dinucleotide phosphate (NADP) is reported. Installation and maintenance of sensitive phosphate and pyridinium functionalities were key to success. Significantly, conversion of NADP into the important mammalian second messenger NAADP was achieved. The graph shows the biological evaluation of the activity of the release of Ca2+ ions, which confirms the identity of NAADP

Convergent synthesis and unexpected Ca(2+)-mobilizing activity of 8-substituted analogues of cyclic ADP-carbocyclic-ribose, a stable mimic of the Ca(2+)-mobilizing second messenger cyclic ADP-ribose.

Cyclic ADP-carbocyclic-ribose (cADPcR, 2) is a biologically and chemically stable equivalent of cyclic ADP-ribose (cADPR, 1), a Ca(2+)-mobilizing second messenger. In this study, a series of 8-substituted analogues of cADPcR, namely the 8-chloro analogue 6 (8-Cl-cADPcR), the 8-azido analogue 7 (8-N(3)-cADPcR), the 8-amino analogue 8 (8-NH(2)-cADPcR), and the 8-phenylthio analogue 9 (8-SPh-cADPcR), were designed as effective pharmacological tools for studies on cADPR-modulated Ca(2+) signaling pathways. These target compounds were synthesized by a convergent route via 8-Cl-cADPcR bisacetonide (14) as the common intermediate, in which a method for forming the intramolecular pyrophosphate linkage by activation of the phenylthiophosphate type substrate 15 with AgNO(3) to produce 14 was used as the key step. The carbocyclic analogues were tested for activity in the sea urchin egg homogenate system. Compounds were assessed for their calcium-mobilizing effects and their ability to cross-desensitize with calcium release induced by a normally maximal concentration of cADPR, as well as cADPR antagonism of cADPR-evoked calcium release. While cADPcR was 3-4 times more potent than cADPR, the 8-substituted analogues were less efficacious, with 8-SPh-cADPcR largely acting as a competitive antagonist. Most surprisingly, given that 8-N(3)-cADPR and 8-NH(2)-cADPR are known as potent antagonists, 8-N(3)-cADPcR and 8-NH(2)-cADPcR were full agonists, but ca. 80 and 2 times less potent than cADPR, respectively. These data contribute to developing structure-activity relationships for the interaction of cADPR with its receptor

Cell-permeant small-molecule modulators of NAADP-mediated Ca2+ release.

Nicotinic acid adenine dinucleotide phosphate (NAADP, 1) is the most potent intracellular Ca2+ mobilizing agent in important mammalian cells and tissues, yet the identity of the NAADP receptor is elusive. Significantly, the coenzyme NADP is completely inactive in this respect. Current studies are restricted by the paucity of any chemical probes beyond NAADP itself, and importantly, none is cell permeant. We report simple nicotinic acid-derived pyridinium analogs as low molecular weight compounds that (1) inhibit Ca2+ release via the NAADP receptor (IC50 approximately 15 microM - 1 mM), (2) compete with NAADP binding, (3) cross the cell membrane of sea urchin eggs to inhibit NAADP-evoked Ca2+ release, and (4) selectively ablate NAADP-dependent Ca2+ oscillations induced by the external gastric peptide hormone agonist cholecystokinin (CCK) in murine pancreatic acinar cells