Ontogeny of cerebral dominance: Evidence from time-sharing asymmetry in children.

Used a dual-task procedure as a measure of speech lateralization in 151 normal, right-handed, 3–12 yr old children. Ss engaged in unimanual finger tapping with and without concurrent speech. It was hypothesized that if speech is left lateralized, talking should disrupt right-hand tapping (an instance of intrahemispheric interference) more than left-hand tapping (an instance of interhemispheric interference). Results for 2 different verbal tasks show the predicted overall asymmetry but no developmental trend in degree of asymmetry. The data suggest that lateralization is as marked in young children as in older children. About 70% of the Ss showed the predicted effect; there was no significant change in incidence as a function of grade level. Analyses of verbal production indicated that the performance asymmetry could not be attributed to an asymmetrical trade-off between talking and tapping. No sex differences in performance asymmetry were found. The results contradict the traditional model of progressive lateralization but corroborate the developmental invariance frequently observed using perceptual measures of language lateralization. (46 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lateral diffusion in planar lipid bilayers

Direct measurements by fluorescence correlation spectroscopy of lateral diffusion coefficients of fluorescent lipid analogs in lipid bilaryer membranes indicate self-diffusion coefficients D greater than 10(-7) square centimeters per second for various lipid systems above their reported transition temperatures. Cholesterol in egg lecithin at mole ratio of 1 : 2 reduces D by about twofold, while retained hydrocarbon solvent can increase it by two- to threefold.     

The retinoid ligand 4-oxo-retinoic acid is a highly active modulator of positional specification

Retinoids (vitamin A and its metabolites) are suspected of regulating diverse aspects of growth, differentiation, and patterning during embryogenesis, but many questions remain about the identities and functions of the endogenous active retinoids involved. The pleiotropic effects of retinoids may be explained by the existence of complex signal transduction pathways involving diverse nuclear receptors of the retinoic acid receptor (RAR) and retinoid X receptor (RXR) families, and at least two types of cellular retinoic acid binding proteins (CRABP-I and -II). The different RARs, RXRs, and CRABPs have different expression patterns during vertebrate embryogenesis, suggesting that they each have particular functions. Another level at which fine tuning of retinoid action could occur is the metabolism of vitamin A to active metabolites, which may include all-trans-retinoic acid, all-trans-3,4-didehydroretinoic acid, 9-cis-retinoic acid, and 14-hydroxy-4,14-retroretinol. Formation of the metabolite all-trans-4-oxo-retinoic acid from retinoic acid was considered to be an inactivation pathway during growth and differentiation. We report here that, in contrast, 4-oxo-retinoic acid is a highly active metabolite which can modulate positional specification in early embryos. We also show that this retinoid binds avidly to and activates RAR beta, and that it is available in early embryos. The different activities of 4-oxo-retinoic acid and retinoic acid in modulating positional specification on the one hand, and growth and differentiation on the other, interest us in the possibility that specific retinoid ligands regulate different physiological processes in vivo.     

HIV protease inhibitory bis-benzamide cyclic ureas: a quantitative structure-activity relationship analysis

A series of N,N'-disubstituted cyclic urea 3-benzamides has been synthesized and evaluated for HIV protease inhibition and antiviral activity. Some of these benzamides have been shown to be potent inhibitors of HIV protease with Ki < 0.050 nM and IC90 < 20 nM for viral replication and, as such, may be useful in the treatment of AIDS. The synthesis and quantitative structure-activity relationship for this benzamide series will be discussed.     

Activity measurements support dimensional assessment

The Diagnostic and Statistical Manual approach to motor excess has been to treat it as a categorical variable whose presence functions as an inclusion criterion. Motor excess is thought to occur primarily during structured settings that maximize attentional demands. Activity is rarely measured as a dimensional attribute despite availability of a wide variety of suitable instruments for more than a decade (Tryon, 1985). The present study measured activity using electronic step counters in structured and unstructured school settings, commuting from home to school and back home, and at home for 2 consecutive weeks in 60 children selected from 450 children using Factor IV (hyperactivity) scores from the Conners Teacher Rating Scale to represent three levels of hyperactivity. Results indicate that (a) children rated as hyperactive are measurably more active than children rated as normally active in unstructured as well as structured situations, (b) measured activity correlates consistently and substantially with rated activity in unstructured and structured situations, and (c) a single activity factor characterizes measured activity in all situations except for class transitions during school. These results and other published findings support a quantitative (dimensional) rather than qualitative (categorical) approach to motor excess.     

Comparison of anion gap and strong ion gap as predictors of unmeasured strong ion concentration in plasma and serum from horses

OBJECTIVE: To compare the accuracy of anion gap (AG) and strong ion gap (SIG) for predicting unmeasured strong ion concentration in plasma and serum from horses. ANIMALS: 6 well-trained Standardbred horses undergoing high-intensity exercise (experimental study) and 78 horses and ponies that underwent i.v. administration of lactic acid or endotoxin, and endurance, submaximal, or high-intensity exercise. PROCEDURE: Anion gap was calculated as AG = (Na+ + K+) - (Cl- + HCO3-), and SIG was calculated, using the simplified strong ion model, whereby SIG (mEq/L) = 2.24 x total protein (g/dl)/(1 + 10(6.65-pH)) - AG. The relation between AG or SIG and plasma lactate concentration was evaluated, using linear regression analysis. RESULTS: Linear relations between plasma lactate concentration and AG and SIG were strong for the experimental study (r2 = 0.960 and 0.966, respectively) and the published studies (r2 = 0.914 and 0.925, respectively). The following relations were derived: AG = 1.00 x plasma lactate + 10.5; SIG = 0.99 x plasma lactate + 2.8. An AG > 15 mEq/L indicated an increased unmeasured anion concentration, whereas a SIG < -2 mEq/L indicated an increased unmeasured strong anion concentration. CONCLUSIONS AND CLINICAL RELEVANCE: Anion gap and SIG can be used to predict plasma lactate concentration in horses. AG is accurate and clinically useful for estimating unmeasured strong ion concentration in horses with total protein concentrations within or slightly outside reference range, whereas SIG is more accurate in horses with markedly abnormal total protein concentrations and those of various ages and with various concentrations of albumin, globulin, and phosphate.     

Self-efficacy beliefs and change in cognitive performance: MacArthur studies on Successful Aging.

Data from a cohort of relatively high functioning, older men and women were used to test the hypothesis that stronger self-efficacy beliefs predict better maintenance of cognitive performance. Structural equation modeling revealed that stronger baseline instrumental efficacy beliefs predicted better verbal memory performance at follow-up among men but not among women, controlling for baseline verbal memory score and sociodemographic and health status characteristics. For both men and women there were no significant associations between either type of self-efficacy beliefs and measures of nonverbal memory, abstraction, or spatial ability. Consistent with previous research showing relationships between baseline cognitive performance and change in self-efficacy beliefs, better abstraction ability was also predictive of increases in instrumental efficacy beliefs among the men. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

From famine to feast: the role of methylglyoxal production in Escherichia coli

Intestinal epithelial cell differentiation is closely regulated during normal cell renewal, maturation, and malignant transformation. Since tyrosine phosphorylation influences differentiation in other cell types and has been reported to vary between crypt cells to differentiated villus tip cells, we investigated the influence of tyrosine phosphorylation in colonocyte differentiation, by using human colonic Caco-2 cells as a model and expression of the brush border enzymes alkaline phosphatase (AKP) and dipeptidyl peptidase (DPDD) as differentiation markers. We studied three tyrosine kinase inhibitors with different modes of action and specificities, viz., genistein, erbstatin analog (EA), and tyrphostin, and the tyrosine phosphatase inhibitor sodium orthovanadate. AKP- and DPDD-specific activities were assayed in protein-matched cell lysates by synthetic substrate digestion. We also correlated the effects of these agents on brush border enzyme activity with tyrosine phosphorylation of phosphoproteins by Western blotting. Genistein (5-75 mg/ml) dose-dependently stimulated AKP and DPDD with a maximal stimulation at 75 mg/ml by 158.6+/- 17.5% and 228.6+/-37.1% of control values, respectively (n=12, P<0.001). The inactive analog genistin had no effect. Tyrphostin (25 mM) similarly stimulated AKP and DPDD by 138. 6+/-6.6% and 131.8+/-1.5% of control values (n=12, P<0.001). Unexpectedly, EA (0.1-10 mM) had the opposite effect, inhibiting AKP- and DPDD-specific activity significantly at 10 mM with a maximal 14.8+/-6.4% and 26.5+/-2.5% of control values (n=12, each P<0.001). Sodium orthovanadate had a discordant effect on these two differentiation markers. Orthovanadate dose-dependently increased AKP to a maximal 188.5+/-16.1% of basal activity at 1.5 mM but decreased DPDD activity at 1.5 mM to 47.2+/-3.8% (n=9, P<0.001 each). The effects of each agent were preserved when proliferation was blocked with mitomycin C, suggesting that the modulation of phenotype by these agents was independent of any effects of proliferation. The tyrosine phosphorylation of several phosphoprotein bands was affected differently by these agents. In particular, the tyrosine phosphorylation of one 70-kDa to 71-kDa band was increased by genistein and tyrophostin but deceased by EA. The different effects of these modulators of tyrosine kinase activity raise the possibility that at least two independent enzymes or pathways regulating tyrosine phosphorylation modulate intestinal epithelial differentiation. Furthermore, tyrosine phosphorylation of the 70-kDa to 71-kDa phosphoprotein may be important in the intracellular signaling by which intestinal epithelial cell differentiation is controlled.