Receptor activity-modifying protein-directed G protein signaling specificity for the calcitonin gene-related peptide family of receptors

The calcitonin gene-related peptide (CGRP) family of G protein- coupled receptors (GPCRs) is formed through the association of the calcitonin receptor-like receptor (CLR) and one of three receptor activity-modifying proteins (RAMPs). Binding of one of the three peptide ligands, CGRP, adrenomedullin (AM), and intermedin/adrenomedullin 2 (AM2), is well known to result in aGαs-mediated increase in cAMP. Here we used modified yeast strains that couple receptor activation to cell growth, via chimeric yeast/Gα subunits, and HEK-293 cells to characterize the effect of different RAMP and ligand combinations on this pathway. We not only demonstrate functional couplings to both Gαs and Gαq but also identify a Gαi component to CLR signaling in both yeast and HEK-293 cells, which is absent in HEK-293S cells. We show that the CGRP family of receptors displays both ligand- and RAMPdependent signaling bias among the Gαs, Gαi, and Gαq/11 pathways. The results are discussed in the context of RAMP interactions probed through molecular modeling and molecular dynamics simulations of the RAMP-GPCR-G protein complexes. This study further highlights the importance of RAMPs to CLR pharmacology and to bias in general, as well as identifying the importance of choosing an appropriate model system for the study of GPCR pharmacology.

El idioma inglés en el currículo universitario: importancia, retos y alcances

Recibido 07 de agosto de 2009 • Aceptado 14 de setiembre de 2009 • Corregido 23 de julio de 2010 La importancia de la inclusión del idioma inglés en el currículo universitario está basada en las exigencias de la globalización e intercambios de mercado, por lo que se cree necesaria la formación del idioma inglés en los estudiantes como futuros profesionales que contribuirán al desarrollo integral de la nación.

ANÁLISE DO USO DO SOLO E SUA RELAÇÃO COM O RELEVO NO MUNICÍPIO DE AGUDO, RS

O trabalho apresenta a organização espacial do uso da terra no município de Agudo-RS. Pode-se ver que a ocupação tem uma forte relação com relevo. A atividade de cultivo de arroz está em áreas de baixa declividade(menos de 5%), constituído por rampas, cultivo de tabaco realiza-se em porções de declividades intermediárias(menos de 15 %), as colinas,e a presença de árvores é concentrada em áreas de encostas (mais de 30%), morros e associações de colina. Proposta para ocupação do atual município, envolvem estudos de características físicas e ambientais.This paper presents the spatial organization of the land use in the county of Agudo-RS.  One can see that the occupation has a strong relationship with relief, thus, the activity of rice cultivation in areas consisting of low slope, the ramps (less than 5%), tabacco farming in portions of intermediate slopes, the hills (less than 15%) and the presence of trees is concentrated in areas of steep slopes, associations of hills and hillock (more than 30%). Proposition to occupation of the current council, involve studies of  physical and environmental characteristics.