Environmental Effects on Cognitive Performance in a 6 to 14 Month-Old Child Population.

The use of the A not B task with delays is presented as an instrument for the evaluation of cognitive performance depending on the prefrontal dorsolateral cerebral cortex. This task was admnistered to 250 children from 6 to 14 months old, from different socio-economical rearing environments (as classified by the Instituto Nacional de Estadística y Censo, INDEC). Results showed an impact of environmental variables on child performance: as a group children from homes providing unsatisfied basic needs homes were less efficient than those who were reared in homes in which their basic needs were satisfied

Migration of Th1 Lymphocytes Is Regulated by CD152 (CTLA-4)-Mediated Signaling via PI3 Kinase-Dependent Akt Activation

Efficient adaptive immune responses require the localization of T lymphocytes in secondary lymphoid organs and inflamed tissues. To achieve correct localization of T lymphocytes, the migration of these cells is initiated and directed by adhesion molecules and chemokines. It has recently been shown that the inhibitory surface molecule CD152 (CTLA-4) initiates Th cell migration, but the molecular mechanism underlying this effect remains to be elucidated. Using CD4 T lymphocytes derived from OVA-specific TCR transgenic CD152-deficient and CD152-competent mice, we demonstrate that chemokine-triggered signal transduction is differentially regulated by CD152 via phosphoinositide 3-kinase (PI3K)-dependent activation of protein kinase B (PKB/Akt). In the presence of CD152 signaling, the chemoattractant CCL4 selectively induces the full activation of Akt via phosphorylation at threonine 308 and serine 473 in pro-inflammatory Th lymphocytes expressing the cognate chemokine receptor CCR5. Akt signals lead to cytoskeleton rearrangements, which are indispensable for migration. Therefore, this novel Akt-modulating function of CD152 signals affecting T cell migration demonstrates that boosting CD152 or its down-stream signal transduction could aid therapies aimed at sensitizing T lymphocytes for optimal migration, thus contributing to a precise and effective immune response

Quantitative Modeling of GRK-Mediated β2AR Regulation

We developed a unified model of the GRK-mediated β2 adrenergic receptor (β2AR) regulation that simultaneously accounts for six different biochemical measurements of the system obtained over a wide range of agonist concentrations. Using a single deterministic model we accounted for (1) GRK phosphorylation in response to various full and partial agonists; (2) dephosphorylation of the GRK site on the β2AR; (3) β2AR internalization; (4) recycling of the β2AR post isoproterenol treatment; (5) β2AR desensitization; and (6) β2AR resensitization. Simulations of our model show that plasma membrane dephosphorylation and recycling of the phosphorylated receptor are necessary to adequately account for the measured dephosphorylation kinetics. We further used the model to predict the consequences of (1) modifying rates such as GRK phosphorylation of the receptor, arrestin binding and dissociation from the receptor, and receptor dephosphorylation that should reflect effects of knockdowns and overexpressions of these components; and (2) varying concentration and frequency of agonist stimulation “seen” by the β2AR to better mimic hormonal, neurophysiological and pharmacological stimulations of the β2AR. Exploring the consequences of rapid pulsatile agonist stimulation, we found that although resensitization was rapid, the β2AR system retained the memory of the previous stimuli and desensitized faster and much more strongly in response to subsequent stimuli. The latent memory that we predict is due to slower membrane dephosphorylation, which allows for progressive accumulation of phosphorylated receptor on the surface. This primes the receptor for faster arrestin binding on subsequent agonist activation leading to a greater extent of desensitization. In summary, the model is unique in accounting for the behavior of the β2AR system across multiple types of biochemical measurements using a single set of experimentally constrained parameters. It also provides insight into how the signaling machinery can retain memory of prior stimulation long after near complete resensitization has been achieved

G protein–coupled receptor kinase 2 (GRK2) modulation and cell cycle progression

Cell cycle progression requires changes in the activity or levels of a variety of key signaling proteins. G protein–coupled receptor kinase 2 (GRK2) plays a central role in G protein–coupled receptor regulation. Recent research is uncovering its involvement in additional cellular functions, but the potential role of GRK2 in the cell cycle has not been addressed. We report that GRK2 protein levels are transiently down-regulated during the G2/M transition by a mechanism involving CDK2-mediated phosphorylation of GRK2 at Serine670, which triggers binding to the prolyl-isomerase Pin1 and subsequent degradation. Prevention of GRK2 phosphorylation at S670 impedes normal GRK2 down-regulation and markedly delays cell cycle progression. Interestingly, we find that endogenous GRK2 down-regulation is prevented on activation of the G2/M checkpoint by doxorubicin and that stabilized GRK2 levels in such conditions inversely correlate with the p53 response and the induction of apoptosis, suggesting that GRK2 participates in the regulatory network controlling cell cycle arrest and survival in such conditions

Learning Vague Knowledge from Socially Generated Content in an Enterprise Framework

Part 7: First Mining Humanistic Data Workshop (MHDW 2012)International audienceThe advent and wide proliferation of Social Web in the recent years has promoted the concept of social interaction as an important influencing factor of the way enterprises and organizations conduct business. Among the fields influenced is that of Enterprise Knowledge Management, where adoption of social computing approaches aims at increasing and maintaining at high levels the active participation of users in the organization’s knowledge management activities. An important challenge towards this is the achievement of the right balance between informalities of socially generated data and the required formality of enterprise knowledge. In this context, we focus on the problem of mining vague knowledge from social content generated within an enterprise framework and we propose a learning framework based on microblogging and fuzzy ontologies

An easy-to-use, operator-independent, clinical model to predict the left vs. right ventricular outflow tract origin of ventricular arrhythmias

Cardiolog

Predictors of Zero X-Ray Ablation for Supraventricular Tachycardias in a Nationwide Multicenter Experience

BACKGROUND: This multicenter, prospective study evaluated the determinants of zero-fluoroscopy (ZFL) ablation of supraventricular tachycardias.METHODS AND RESULTS: Four hundred thirty patients (215 male, 55.4 +/- 22.1 years) with indication to electrophysiological study or ablation of supraventricular tachycardias were enrolled. All participating physicians agreed to follow the as low as reasonably achievable policy. A procedure was defined as ZFL when no fluoroscopy was used. The total fluoroscopy time inversely correlated to the number of procedures previously performed by each operator since study start (r=-0.112; P=0.02). Two hundred eighty-nine procedures (67.2%) were ZFL; multivariable analysis identified as predictors of ZFL: procedure after the 30th for each operator, compared with procedures up to the ninth (P=0.011; hazard ratio, 3.49; 95% confidence interval [ CI], 1.79-6.80); the type of arrhythmia (P=0.031; electrophysiological study and atrioventricular nodal reentry tachycardia ablation having the highest probability of ZFL; hazard ratio, 6.87; 95% CI, 2.08-22.7 and hazard ratio, 2.02; 95% CI, 1.04-3.91, respectively); the operator's (P=0.002) and patient's age (P=0.009). Among operators, achievement of ZFL varied from 0% to 100%; 8 (22.8%) operators achieved ZFL in <25% of their procedures; 17 (48.6%) operators achieved ZFL in >75% of their procedures. The probability of ZFL increased by 2.8% (hazard ratio, 0.98; 95% CI, 0.97-0.99) as patient's age decreased by 1 year. Acute procedural success was obtained in all cases.CONCLUSIONS: The use of 3-dimensional mapping system completely avoided the use of fluoroscopy in most cases, with very low fluoroscopy time in the remaining and high safety and effectiveness profiles. Achievement of ZFL was predicted by the type of arrhythmia, operator's experience, and patient's ag