LIBERTAÇÃO NAS TRILHAS DA JUSTIÇA: Estudo histórico e hermenêutico de Isaías 42,1-4

O presente trabalho tem como objetivo propor um estudo do cântico do escravo de Javé em Isaías 42,1- 4. Javé apresenta uma nova liderança, com um novo jeito de pensar e de agir para reconstruir um mundo novo baseado no direito e na solidariedade. É uma tarefa desafiadora para mim e ao mesmo tempo uma alegria em poder compartilhar com os meus amigos o conteúdo de um texto do Antigo Testamento. Afinal, o cântico do escravo de Javé é uma fonte inesgotável de sabedoria. Saciou o povo judaíta exilado a de dois mil e quinhentos anos atrás e continua jorrando água viva até em nossos dias matando a sede de todos aqueles e aquelas que lutam pela justiça. Os versos escolhidos são frutos de uma experiência de vida concreta dos exilados desacreditados por todos no cativeiro da Babilônia. No fundo é uma crítica aos falsos deuses criados pelos poderosos para justificar um sistema de opressão. A criatividade do profeta está em retomar os eventos históricos que marcaram a vida do povo exilado e atualizá-los dentro de um novo contexto histórico. Isto demonstra sua agilidade no conhecimento. Cada palavra é pensada dentro de um contexto maior envolvendo a vida e a história. O profeta é um sábio poeta, que fala de Deus como ninguém falou antes. Utiliza símbolos, imagens e metáforas que apontam para um mundo novo que ainda não existe, onde reinará o direito, a justiça e a paz. Essa mudança acontecerá a partir da missão que a liderança eleita desempenhará junto do povo oprimido e injustiçado. O líder será como o fermento na massa para a nova sociedade, baseada na igualdade e na partilha. O espírito de Javé estará agindo sobre ele para que ele não desanime da missão e que ela possa alcançar o seu objetivo. Essa nova liderança eleita por Javé agirá discretamente em silêncio entre os pobres e enfraquecidos. A missão beneficiará primeiramente às nações. Aqueles e aquelas que vivem em terras estrangeiras como migrantes. Depois contemplará de modo especial os pobres que estão correndo risco de vida, cana rachada e pavio vacilante e por fim a missão atingirá todos os povos da terra. Essa perspectiva traduz a vontade de Deus que é a salvação de toda a humanidade.(AU)

Defects in inositol 1,4,5-trisphosphate receptor expression, Ca2+ signaling, and insulin secretion in the anx7(+/−) knockout mouse

The mammalian anx7 gene codes for a Ca2+-activated GTPase, which supports Ca2+/GTP-dependent secretion events and Ca2+ channel activities in vitro and in vivo. To test whether anx7 might be involved in Ca2+ signaling in secreting pancreatic β cells, we knocked out the anx7 gene in the mouse and tested the insulin-secretory properties of the β cells. The nullizygous anx7 (−/−) phenotype is lethal at embryonic day 10 because of cerebral hemorrhage. However, the heterozygous anx7 (+/−) mouse, although expressing only low levels of ANX7 protein, is viable and fertile. The anx7 (+/−) phenotype is associated with a substantial defect in insulin secretion, although the insulin content of the islets, is 8- to 10-fold higher in the mutants than in the normal littermate control. We infer from electrophysiological studies that both glucose-stimulated secretion and voltage-dependent Ca2+ channel functions are normal. However, electrooptical recordings indicate that the (+/−) mutation has caused a change in the ability of inositol 1,4,5-trisphosphate (IP3)-generating agonists to release intracellular calcium. The principle molecular consequence of lower anx7 expression is a profound reduction in IP3 receptor expression and function in pancreatic islets. The profound increase in islets, β cell number, and size may be a means of compensating for less efficient insulin secretion by individual defective pancreatic β cells. This is a direct demonstration of a connection between glucose-activated insulin secretion and Ca2+ signaling through IP3-sensitive Ca2+ stores.

The increased level of β1,4-galactosyltransferase required for lactose biosynthesis is achieved in part by translational control

β1,4-Galactosyltransferase (β4GalT-I) participates in both glycoconjugate biosynthesis (ubiquitous activity) and lactose biosynthesis (mammary gland-specific activity). In somatic tissues, transcription of the mammalian β4GalT-I gene results in a 4.1-kb mRNA and a 3.9-kb mRNA as a consequence of initiation at two start sites separated by ≈200 bp. In the mammary gland, coincident with the increased β4GalT-I enzyme level (≈50-fold) required for lactose biosynthesis, there is a switch from the 4.1-kb start site to the preferential use of the 3.9-kb start site, which is governed by a stronger tissue-restricted promoter. The use of the 3.9-kb start site results in a β4GalT-I transcript in which the 5′- untranslated region (UTR) has been truncated from ≈175 nt to ≈28 nt. The 5′-UTR of the 4.1-kb transcript [UTR(4.1)] is predicted to contain extensive secondary structure, a feature previously shown to reduce translational efficiency of an mRNA. In contrast, the 5′-UTR of the 3.9-kb mRNA [UTR(3.9)] lacks extensive secondary structure; thus, this transcript is predicted to be more efficiently translated relative to the 4.1-kb mRNA. To test this prediction, constructs were assembled in which the respective 5′-UTRs were fused to the luciferase-coding sequence and enzyme levels were determined after translation in vitro and in vivo. The luciferase mRNA containing the truncated UTR(3.9) was translated more efficiently both in vitro (≈14-fold) and in vivo (3- to 5-fold) relative to the luciferase mRNA containing the UTR(4.1). Consequently, in addition to control at the transcriptional level, β4GalT-I enzyme levels are further augmented in the lactating mammary gland as a result of translational control.

Modulation of Ca2+ entry by polypeptides of the inositol 1,4,5-trisphosphate receptor (IP3R) that bind transient receptor potential (TRP): Evidence for roles of TRP and IP3R in store depletion-activated Ca2+ entry

Homologues of Drosophilia transient receptor potential (TRP) have been proposed to be unitary subunits of plasma membrane ion channels that are activated as a consequence of active or passive depletion of Ca2+ stores. In agreement with this hypothesis, cells expressing TRPs display novel Ca2+-permeable cation channels that can be activated by the inositol 1,4,5-trisphosphate receptor (IP3R) protein. Expression of TRPs alters cells in many ways, including up-regulation of IP3Rs not coded for by TRP genes, and proof that TRP forms channels of these and other cells is still missing. Here, we document physical interaction of TRP and IP3R by coimmunoprecipitation and glutathione S-transferase-pulldown experiments and identify two regions of IP3R, F2q and F2g, that interact with one region of TRP, C7. These interacting regions were expressed in cells with an unmodified complement of TRPs and IP3Rs to study their effect on agonist- as well as store depletion-induced Ca2+ entry and to test for a role of their respective binding partners in Ca2+ entry. C7 and an F2q-containing fragment of IP3R decreased both forms of Ca2+ entry. In contrast, F2g enhanced the two forms of Ca2+ entry. We conclude that store depletion-activated Ca2+ entry occurs through channels that have TRPs as one of their normal structural components, and that these channels are directly activated by IP3Rs. IP3Rs, therefore, have the dual role of releasing Ca2+ from stores and activating Ca2+ influx in response to either increasing IP3 or decreasing luminal Ca2+.