Intramolecular energies of the cytotoxic protein CagA of Helicobacter pylori as a possible descriptor of strains' pathogenicity level.

The Helicobacter pylori cytotoxin-associated gene A (CagA) is known for causing gastroduodenal diseases, such as atrophic gastritis and peptic ulcerations. Furthermore Helicobacter pylori CagA positive strains has been reported as one of the main risk factors for gastric cancer (Parsonnet et al., 1997). Structural variations in the CagA structure can alter its affinity with the host proteins, inducing differences in the pathogenicity of H. pylori. CagA N-terminal region is characterized for be conserved among all H. pylori strains since the C-terminal region is characterized by an intrinsically disorder behavior. We generated complete structural models of CagA using different conformations of the C-terminal region for two H. pylori strains. These models contain the same EPIYA (ABC1C2) motifs but different level of pathogenicity: gastric cancer and duodenal ulcer. Using these structural models we evaluated the pathogenicity level of the H. pylori strain, based on the affinity of the interaction with SHP-2 and Grb2 receptors and on the number of interactions with the EPIYA motif. We found that the main differences in the interaction was due to the contributions of certain types of energies from each strain and not from the total energy of the molecule. Specifically, the electrostatic energy, helix dipole energy, Wander Waals clashes, torsional clash, backbone clash and cis bond energy allowed a separation between severe and mild pathology for the interaction of only CagA with SHP2.

Computational approaches for evaluating the effect of sequence variations and the intrinsically disordered C-terminal region of the Helicobacter pylori CagA protein on the interaction with tyrosine kinase Src.

The Helicobacter pylori CagA protein was the first bacterial oncoprotein to be identified as important in the development of human malignancies such as gastric cancer. It is not clear how it is able to deregulate a set of cell control mechanisms to induce carcinogenesis following translocation into human gastric epithelial cells. It is likely, however, that structural variations in the CagA sequence alter its affinity with the host proteins inducing differences in the pathogenicity of different H. pylori strains. Using the recently elucidated N-terminal 3D structure of H. pylori CagA, information on the full cagA gene sequence, and intrinsically disordered protein structure predictions methods we evaluated the interaction of different CagA variants with the kinase Src. An automated docking followed by molecular dynamics simulations were performed to explore CagA interaction modes with Src, one of its cellular partners. The computational approach let us establish that even in the presence of the same number and type of EPIYA motifs, CagA protein can reveal different spatial distributions. Based on the lowest affinity energy and higher number of interactions it was established that the principal forces governing the CagA-Src interaction are electrostatic. Results showed that EPIYA-D models presents higher affinity with some host proteins than EPIYA-C. Thus, we highlight the importance and advantage of the use of computational tools in combining chemical and biological data with bioinformatics for modeling and prediction purposes in some cases where experimental techniques present limitations.

Predominio del "cerebro triádico" de acuerdo a niveles de desempeño estratégico de un grupo de trabajadores colombianos / Predominance of "triadic brain" according to levels of strategic performance of Colombian workers group

RESUMEN Introducción: Las organizaciones poseen herramientas válidas que ayudan al reconocimiento de los neurotalentos, proporcionando elementos de selección de personal y desarrollo estratégico. Objetivo: Evaluar el predominio cerebral de un grupo de trabajadores de acuerdo a su nivel de desempeño estratégico, basado en la teoría del "cerebro tríadico". Métodos: Estudio descriptivo-evaluativo, multicéntrico, enfoque cuantitativo, diseño no experimental realizado en una muestra de 68 trabajadores, de las ciudades de Sincelejo y Rioacha; seleccionados de manera no probabilística y que desempeñan actividades en diferentes niveles estratégicos. La recogida de datos se hizo mediante el test revelador del cociente mental tríadico diseñado por Waldemar De Gregory, el análisis se hizo mediante estadígrafos descriptivos. Resultados: La mayoría de trabajadores pertenece al sexo femenino (60 por ciento), desempeñan cargos misionales (73,8 por ciento), poseen predominancia de cerebro central (46,0 por ciento), escala de medición superior. Conclusiones: El predomino de cerebro tríadico corresponde al cerebro central con un nivel superior y desarrollo de actividades de nivel estratégico misional(AU)

ABSTRACT Introduction: Organizations have valid tools that help the recognition of nurotalentos providing elements of recruitment and strategic development. Objectives: Assess brain dominance of a group of workers according to their level of strategic performance, based on the theory of "Brain triadic". Methods: Evaluative descriptive, multicenter study, quantitative approach, no experimental design; conducted on a sample of 68 workers selected probabilistically and not engaged in activities at different strategic levels. Data collection was done by the developer test triadic mental quotient (RCMT) designed by Waldemar De Gregory. Results: Most workers are female (60 percent), missionary positions (73.8 percent), central brain predominance (46.0 percent) and higher measurement scale. Conclusions: predominance of the central brain, higher level and strategic level missionary activities evidenced(AU)