2 resultados para Ayrer, Jean-Christophe (16..-16..) -- Portraits

em Biblioteca Digital da Produção Intelectual da Universidade de São Paulo


Relevância:

100.00% 100.00%

Publicador:

Resumo:

This meta-analysis of land-cover transformations of the past 10-15 years in tropical forest-agriculture frontiers world-wide shows that swidden agriculture decreases in landscapes with access to local, national and international markets that encourage cattle production and cash cropping, including biofuels. Conservation policies and practices also accelerate changes in swidden by restricting forest clearing and encouraging commercial agriculture. However, swidden remains important in many frontier areas where farmers have unequal or insecure access to investment and market opportunities, or where multi-functionality of land uses has been preserved as a strategy to adapt to current ecological, economic and political circumstances. In some areas swidden remains important simply because intensification is not a viable choice, for example when population densities and/or food market demands are low. The transformation of swidden landscapes into more intensive land uses has generally increased household incomes, but has also led to negative effects on the social and human capital of local communities to varying degrees. From an environmental perspective, the transition from swidden to other land uses often contributes to permanent deforestation, loss of biodiversity, increased weed pressure, declines in soil fertility, and accelerated soil erosion. Our prognosis is that, despite the global trend towards land use intensification, in many areas swidden will remain part of rural landscapes as the safety component of diversified systems, particularly in response to risks and uncertainties associated with more intensive land use systems. (C) 2011 Elsevier Ltd. All rights reserved.

Relevância:

50.00% 50.00%

Publicador:

Resumo:

The recent discovery that peroxisome proliferator-activated receptor gamma (PPAR gamma) targeted anti-diabetic drugs function by inhibiting Cdk5-mediated phosphorylation of the receptor has provided a new viewpoint to evaluate and perhaps develop improved insulin-sensitizing agents. Herein we report the development of a novel thiazolidinedione that retains similar anti-diabetic efficacy as rosiglitazone in mice yet does not elicit weight gain or edema, common side effects associated with full PPAR gamma activation. Further characterization of this compound shows GQ-16 to be an effective inhibitor of Cdk5-mediated phosphorylation of PPAR gamma. The structure of GQ-16 bound to PPAR gamma demonstrates that the compound utilizes a binding mode distinct from other reported PPAR gamma ligands, although it does share some structural features with other partial agonists, such as MRL-24 and PA-082, that have similarly been reported to dissociate insulin sensitization from weight gain. Hydrogen/deuterium exchange studies reveal that GQ-16 strongly stabilizes the beta-sheet region of the receptor, presumably explaining the compound's efficacy in inhibiting Cdk5-mediated phosphorylation of Ser-273. Molecular dynamics simulations suggest that the partial agonist activity of GQ-16 results from the compound's weak ability to stabilize helix 12 in its active conformation. Our results suggest that the emerging model, whereby "ideal" PPAR gamma-based therapeutics stabilize the beta-sheet/Ser-273 region and inhibit Cdk5-mediated phosphorylation while minimally invoking adipogenesis and classical agonism, is indeed a valid framework to develop improved PPAR gamma modulators that retain antidiabetic actions while minimizing untoward effects.