Initial-rate and product inhibition studies revealed distinctive ordered ternary complex kinetic mechanisms, substrate specificities, and metal ion preferences for the three isozymes of human nicotinamide mononucleotide adenylyl-transferase (NMNAT, EC 2.7.7.1). ATP binds before NMN with nuclear isozyme NMNAT1 and Golgi apparatus NMNAT2, but the opposite order is observed with the mitochondrial isozyme NMNAT3. Only the latter utilizes ITP efficiently in place of ATP, and while NMNH conversion to NADH by NMNAT1 and NMNAT3 occurs at similar rates, conversion by NMNAT2 is much slower. These isozymes can also be discriminated by their action on tiazofurin monophosphate (TrMP), a metabolite of the antineoplastic prodrug tiazofurin. Our finding that TrMP is only a substrate with NMNAT1 and NMNAT3 reveals for the first time an organelle selectivity in the metabolism of this important drug. In search of additional ways to discriminate these isozymes, we synthesized and tested the P1-(nicotinamide/nicotinate-riboside-5')-Pn-(adenosine-5') dinucleotides Np3AD, Np4AD, and Nap4AD. In addition to being highly effective inhibitors, these multisubstrate geometric inhibitors gave inhibition patterns that are consistent with the aforementioned isozyme differences in substrate binding order. Distinctive differences in their substrate specificity and metal ion selectivity also permitted us to quantify individual isozyme contributions to NAD+ formation in human cell extracts.

In this study, a series of tests exploring long-term verbal memory (the Short Story Test), attention (a modified version of Attentional Matrices and the Trail Making Test) and frontal functions (a modified version of the Frontal Assessment Battery) have been standardised on an Italian population of 283 children aged 5-14. Raw scores for each test have been adjusted for a series of variables (child's age, years of parents' education, handedness, gender) and transformed in equivalent scores enabling direct comparison across measures. This study was promoted by LICE (the Italian League Against Epilepsy) in order to provide Italian instruments standardised on the developmental age population and to study some of the most frequently impaired cognitive functions in epilepsy.

Background/Aims: In Alzheimer's dementia (AD), letter fluency is less impaired than category fluency. To check whether category fluency and letter fluency depend differently on semantics and attention, 53 mild AD patients were given animal and letter fluency tasks, two semantic tests (the Verbal Semantic Questionnaire and the BORB Association Match test), and two attentional tests (the Stroop Colour-Word Interference test and the Digit Cancellation test). Methods: We conducted a LISREL confirmatory factor analysis to check the extent to which category fluency and letter fluency tasks were related to semantics and attention, viewed as latent variables. Results: Both types of fluency tasks were related to the latent variable Semantics but not to the latent variable Attention. Conclusions: Our findings warn against interpreting the disproportionate impairment of AD patients on category and letter fluency as a contrast between semantics and attention.

Semantic dissociations show that biological stimuli present a further dissociation between animals and plant life. Almost all cases of greater impairment of plant life knowledge were males, suggesting a higher male familiarity with animals possibly derived from different daily activities. To verify this hypothesis, we collected familiarity ratings for normal males and females, for 288 animals, subdivided according to whether they were hunted/fished, or were used as food. The overall familiarity was almost identical between males and females. Males were more familiar with hunted animals, but for them also food animals were more familiar. There was not a consistent effect of hunting/fishing independently of the food/not food classification. The claim that males are generally more proficient with animals knowledge because most hunters/fishers are males seems rather simplistic, and the familiarity structure of the animals category is more complex. An evolution-based account is suggested for the category by sex interaction.