ENTENDENDO O ATIVISMO JUDICIAL A PARTIR DA DOUTRINA DO ACTIVE AVOIDANCE

Embora se reconheça que os modelos jurídicos que empregam o denominado “civil law” sejam identificados pelo emprego da lei e as suas codificações como fonte primária do Direito, em contraponto com o “common law” tendo o costume jurisprudencial como essa fonte, as raízes de ambos os sistemas jurídicos são comuns. Indiscutível que o Brasil busca aproximação com esse sistema, positivando a cultura dos precedentes. Não apenas isso, o Ativismo Judicial tem sua gênese no modelo jurídico de controle de constitucionalidade praticado pela Suprema Corte dos Estados Unidos da América, no sistema de “common law”, que vem sendo replicado em todos os países do “civil law”, inclusive, no Brasil. O Ativismo Judicial foi concebido nos Estados Unidos para solucionar os casos difíceis de dúvida constitucional. No Brasil, replica-se essa metodologia, mas sem a sistematização metodológica desenvolvida na cultura jurisprudencial da Suprema Corte dos Estados Unidos, que favorece muita confusão a respeito da sua natureza jurídica. Portanto, só é possível entender o Ativismo Judicial e a cultura dos precedentes investigando sua origem no sistema de “common law” norte-americano

Low intrinsic efficacy for G protein activation can explain the improved side-effect profile of new opioid agonists

Biased agonism at G protein–coupled receptors describes the phenomenon whereby some drugs can activate some downstream signaling activities to the relative exclusion of others. Descriptions of biased agonism focusing on the differential engagement of G proteins versus β-arrestins are commonly limited by the small response windows obtained in pathways that are not amplified or are less effectively coupled to receptor engagement, such as β-arrestin recruitment. At the μ-opioid receptor (MOR), G protein–biased ligands have been proposed to induce less constipation and respiratory depressant side effects than opioids commonly used to treat pain. However, it is unclear whether these improved safety profiles are due to a reduction in β-arrestin–mediated signaling or, alternatively, to their low intrinsic efficacy in all signaling pathways. Here, we systematically evaluated the most recent and promising MOR-biased ligands and assessed their pharmacological profile against existing opioid analgesics in assays not confounded by limited signal windows. We found that oliceridine, PZM21, and SR-17018 had low intrinsic efficacy. We also demonstrated a strong correlation between measures of efficacy for receptor activation, G protein coupling, and β-arrestin recruitment for all tested ligands. By measuring the antinociceptive and respiratory depressant effects of these ligands, we showed that the low intrinsic efficacy of opioid ligands can explain an improved side effect profile. Our results suggest a possible alternative mechanism underlying the improved therapeutic windows described for new opioid ligands, which should be taken into account for future descriptions of ligand action at this important therapeutic target

Evolution of model proteins on a foldability landscape

We model the evolution of simple lattice proteins as a random walk in a fitness landscape, where the fitness represents the ability of the protein to fold. At higher selective pressure, the evolutionary trajectories are confined to neutral networks where the native structure is conserved and the dynamics are non self-averaging and nonexponential. The optimizability of the corresponding native structure has a strong effect on the size of these neutral networks and thus on the nature of the evolutionary process. Proteins 29:461–466, 1997. © 1997 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38527/1/6_ftp.pd

Arqueologia e história indígena no Pantanal

O artigo apresenta uma síntese dos dados arqueológicos sobre o Pantanal e o seu entorno, principalmente em Mato Grosso e Mato Grosso do Sul. Elaborado com base na noção de arqueologia como história indígena de longa duração, o artigo considera as trajetórias de estabelecimento e consolidação territorial da ocupação indígena regional, os processos de formação da configuração etnográfica encontrada pelos europeus e os impactos do colonialismo. O principal objetivo consiste em mostrar que a diversidade cultural característica do cenário etnográfico pantaneiro está associada à dinâmica histórica e cultural da ocupação indígena desde períodos anteriores à chegada dos conquistadores e colonizadores de origem europeia.The article presents an overview of the archaeological data on the Pantanal and its surrounding areas, mainly in Mato Grosso and Mato Grosso do Sul. Prepared based on the notion of archeology as long term indigenous history, the article considers the trajectories of territorial establishment and consolidation of the regional indigenous occupation, the formation processes of ethnographic setting found by Europeans and the impact of colonialism. The main objective is to show that cultural diversity characteristic of the Pantanal ethnographic scenario is associated with historical and cultural dynamics of indigenous occupation from periods prior to the arrival of the conquistadors and settlers of European origin