Mechanism of anion selectivity and stoichiometry of the Na+/I- symporter (NIS)

I(-) uptake in the thyroid, the first step in thyroid hormone biosynthesis, is mediated by the Na(+)/I(-) symporter (NIS) with an electrogenic 2Na(+):1I(-) stoichiometry. We have obtained mechanistic information on NIS by characterizing the congenital I(-) transport defect-causing NIS mutant G93R. This mutant is targeted to the plasma membrane but is inactive. Substitutions at position 93 show that the longer the side chain of the neutral residue at this position, the higher the K(m) for the anion substrates. Unlike WT NIS, which mediates symport of Na(+) and the environmental pollutant perchlorate electroneutrally, G93T/N/Q/E/D NIS, strikingly, do it electrogenically with a 21 stoichiometry. Furthermore, G93E/Q NIS discriminate between anion substrates, a discovery with potential clinical relevance. A 3D homology model of NIS based on the structure of the bacterial Na(+)/galactose transporter identifies G93 as a critical player in the mechanism of the transporter: the changes from an outwardly to an inwardly open conformation during the transport cycle use G93 as a pivo

Experimental Conversations: Sign Language Studies with Chimpanzees

Sign language studies of chimpanzees are a tool for studying the continuity between human behavior and behavior of other animals and between verbal behavior and other intelligent behavior. Cross-fostered chimpanzees paralleled children in their acquisition and use of signs and phrases. These procedures occurred under rigorous and systematic record keeping and experimental paradigms. The study of Wh-questions and the use of remote videotaping (RVT) are examples of experimental procedures. These revealed chimpanzee-to-chimpanzee signing and private signing. Face-to-face interactions between the chimpanzees and an interlocutor who presented various systematic probes is another experimental procedure. The chimpanzees adjusted to the interlocutor with revisions, new signs, or no response when appropriate. The hallmark of the sign language studies is that caregivers treated the chimpanzees as conversational partners socially motivated rather than experimental subjects bribed or forced into participation. These findings confirm continuity with differences of degree among species