Suppressor of cytokine signaling-2: A growth hormone-inducible inhibitor of intestinal epithelial cell proliferation

AbstractBackground & Aims: Growth hormone (GH) and insulin-like growth factor-I (IGF-I) increase intestinal growth. GH is thought to act indirectly via IGF-I. In several models, including rats given total parenteral nutrition (TPN), IGF-I more potently stimulates mucosal growth than GH, even when GH induces similar circulating IGF-I levels. These studies test the hypothesis that GH induces a suppressor of cytokine signaling (SOCS), which inhibits intestinal epithelial cell (IEC) proliferation. Methods: Rats on TPN received vehicle, GH, or IGF-I. Jejunal SOCS (SOCS-1, -2, -3, and cytokine-inducible SH2-domain-containing protein [CIS]) and IGF-I messenger RNA (mRNA) were quantified. Caco-2, IEC-6 cells, and SOCS-2 null and wild-type (WT) mice were used to examine the expression and functional role of SOCS-2. Results: As reported previously, IGF-I, but not GH, prevented mucosal atrophy during TPN, although GH elevated plasma IGF-I and increased body weight. GH, but not IGF-I, induced jejunal SOCS-2 mRNA. SOCS-2 mRNA levels in GH and IGF-I-treated rats inversely correlated with mucosal weight. SOCS-2 is expressed in Caco-2 cells, and elevated SOCS-2 expression in postconfluent cells is associated with reduced proliferative rates. SOCS-2 overexpression in Caco-2 cells inhibited cell proliferation and promoted differentiation. In IEC-6 cells, GH induced SOCS-2 and reduced basal or IGF-I-induced proliferation. GH also reduced proliferative activity in isolated crypts from WT but not SOCS-2 null mice, and SOCS-2 null crypts showed enhanced proliferative responses to GH and IGF-I. SOCS-2 null mice have increased intestinal weight and length. Conclusions: SOCS-2 is a GH-inducible, novel inhibitor of intestinal epithelial cell proliferation and intestinal growth

The Hermeneutics of Antonio Candido and Angel Rama

A caracterização da crítica de Antonio Candido e Angel Rama como "sociológica", "culturalista" ou "neoarielista" tem sido usada para defini-los como grandes representantes da tradição crítica latino-americana ou, alternativamente, como precursores da agenda dos Estudos Culturais na região. No entanto, uma análise mais apurada dos fundamentos hermenêuticos de sua produção, por meio da filosofia de Gadamer, revela quadro mais complexo, que não se ajusta a essa imagem simplista. Enquanto a maior parte dos teóricos evita a incômoda distinção entre alta e baixa cultura, ou entre literatura como representação cultural e literatura como forma de arte, Candido e Rama abraçaram a tarefa de tentar encontrar os denominadores comuns que ligam esses elementos. Ao fazerem-no, desenvolveram uma abordagem crítica em que conceitos seminais de Gadamer encontram ressonância. O encontro com a tradição, em especial, de fundamental importância para o filósofo alemão, situa-se no centro da obra crítica dos dois autores. E, no entanto, os principais elementos da tradição literária latino-americana e sua conexão com modelos ocidentais não são evidentes. De forma convergente com Gadamer, os dois críticos acreditavam que a atividade crítica, embora subjetiva e profundamente impregnada de história, poderia levar a conhecimento objetivo, capaz de descortinar as intrincadas conexões entre literatura e sociedade. Partindo do princípio de que o sistema literário é constituído pela tríade "autor-obra- público", o crítico não deveria jamais tentar analisar a obra literária de forma isolada. A consolidação da tradição literária latino-americana deveria ser abordada, assim, por meio de uma atitude crítica informada pela consciência histórica, sensibilidade estética e responsabilidade social do analista. Ainda que traços específicos possam ser encontrados na obra de cada um dos autores, essa abordagem, comum aos dois, torna-se particularmente perceptível na crítica de Ruben Darío e Guimarães Rosa. Esses escritores foram saudados por sua capacidade de criar obras de arte ao mesmo tempo representativas de suas sociedades e universais, de acordo com padrões ocidentais. O conceito de "fusão de horizontes", de Gamader, ganha assim uma tradução particular no conceito de "transculturación", de Rama, ou de "super- regionalismo", de Candido. A confluência entre essas formulações e os fundamentos básicos da hermenêutica filosófica de Gamader permite-nos propor uma nova leitura da obra dos críticos latino-americanos. Como o significado e a relevância das obras literárias só podem ser compreendidos adequadamente conferindo-se a devida atenção ao contexto cultural e social específico de sua produção, a literatura só poderá assumir seu caráter latino-americano ao compartilhar das fontes da tradição ocidental. Nesse contexto, o crítico é forçado a se tornar um mediador entre dois mundos.The label of "sociologic", "culturalist" or "neoarielist" attached to the criticism of Antonio Candido and Angel Rama has usually been used to portray them whether as main representatives of the Latin American critical tradition or as forerunners of the agenda of Cultural Studies in the region. Yet a closer look to the hermeneutical foundations of their production through the lenses of Hans-Georg Gadamer’s philosophy reveals a more complex picture, which does not conform to this simplistic image. While most theorists usually eschew the uncomfortable distinction between high and low culture, or between literature as cultural representation and literature as art, Candido and Rama embraced the task of trying to find a common ground between these elements. By doing so, they developed a critical approach in which seminal concepts of Gadamer find resonance. The encounter with tradition, in particular, which is of fundamental importance to the German philosopher, lies at the heart of both critics work. Yet the main elements of the Latin American literary tradition and their connection with western models could not be taken for granted. In agreement with Gadamer, both critics believed that the practice of criticism, although subjective to a certain degree and deeply imbedded in history, might lead to an objective knowledge, which would eventually unveil the intricate connections between literature and society. Bearing in mind that the literary system is constituted by the triad "author-work-public", the critic should never intend to analyze the literary work in isolation. The consolidation of Latin American literary tradition was to be met, hence, by a critical attitude informed by historic awareness, aesthetic sensitivity and social responsibility. Although with particular traits in each author´s work, this approach was common to both. It became particularly noticeable in the critique of Ruben Darío and Guimarães Rosa, who were praised by their capacity to create works of art at the same time representative of their societies and universal, according to western standards. Gadamer's concept of "fusion of horizons" thus found a particular translation in Rama's concept of "transculturación" and Candido's "super-regionalismo". The convergence of these formulations with the main underpinnings of the philosophical hermeneutics of Gadamer allows us to propose a new reading of their work. As the meaning and the relevance of literary works can only be grasped adequately with due attention to the specific social and cultural context of their production, literature can only assume a Latin American character by partaking in the wellspring of western tradition. In this context, the critic is forced to be a mediator between two different worlds himself