Temporal dynamics of verbal object comprehension

Knowledge of the stage composition and the temporal dynamics of human cognitive operations is critical for building theories of higher mental activity. This information has been difficult to acquire, even with different combinations of techniques such as refined behavioral testing, electrical recording/interference, and metabolic imaging studies. Verbal object comprehension was studied herein in a single individual, by using three tasks (object naming, auditory word comprehension, and visual word comprehension), two languages (English and Farsi), and four techniques (stimulus manipulation, direct cortical electrical interference, electrocorticography, and a variation of the technique of direct cortical electrical interference to produce time-delimited effects, called timeslicing), in a subject in whom indwelling subdural electrode arrays had been placed for clinical purposes. Electrical interference at a pair of electrodes on the left lateral occipitotemporal gyrus interfered with naming in both languages and with comprehension in the language tested (English). The naming and comprehension deficit resulted from interference with processing of verbal object meaning. Electrocorticography indices of cortical activation at this site during naming started 250–300 msec after visual stimulus presentation. By using the timeslicing technique, which varies the onset of electrical interference relative to the behavioral task, we found that completion of processing for verbal object meaning varied from 450 to 750 msec after current onset. This variability was found to be a function of the subject’s familiarity with the objects.

The structure of the human βII-tryptase tetramer: Fo(u)r better or worse

Tryptases, the predominant serine proteinases of human mast cells, have recently been implicated as mediators in the pathogenesis of allergic and inflammatory conditions, most notably asthma. Their distinguishing features, their activity as a heparin-stabilized tetramer and resistance to most proteinaceous inhibitors, are perfectly explained by the 3-Å crystal structure of human βII-tryptase in complex with 4-amidinophenylpyruvic acid. The tetramer consists of four quasiequivalent monomers arranged in a flat frame-like structure. The active centers are directed toward a central pore whose narrow openings of approximately 40 Å × 15 Å govern the interaction with macromolecular substrates and inhibitors. The tryptase monomer exhibits the overall fold of trypsin-like serine proteinases but differs considerably in the conformation of six surface loops arranged around the active site. These loops border and shape the active site cleft to a large extent and form all contacts with neighboring monomers via two distinct interfaces. The smaller of these interfaces, which is exclusively hydrophobic, can be stabilized by the binding of heparin chains to elongated patches of positively charged residues on adjacent monomers or, alternatively, by high salt concentrations in vitro. On tetramer dissociation, the monomers are likely to undergo transformation into a zymogen-like conformation that is favored and stabilized by intramonomer interactions. The structure thus provides an improved understanding of the unique properties of the biologically active tryptase tetramer in solution and will be an incentive for the rational design of mono- and multifunctional tryptase inhibitors.