Intrinsic and acquired resistance to chemotherapy is the fundamental reason for treatment failure for many cancer patients. The identification of molecular mechanisms involved in drug resistance or sensitization is imperative. Here we report that tribbles homologue 2 (TRIB2) ablates forkhead box O activation and disrupts the p53/MDM2 regulatory axis, conferring resistance to various chemotherapeutics. TRIB2 suppression is exerted via direct interaction with AKT a key signalling protein in cell proliferation, survival and metabolism pathways. Ectopic or intrinsic high expression of TRIB2 induces drug resistance by promoting phospho-AKT (at Ser473) via its COP1 domain. TRIB2 expression is significantly increased in tumour tissues from patients correlating with an increased phosphorylation of AKT, FOXO3a, MDM2 and an impaired therapeutic response. This culminates in an extremely poor clinical outcome. Our study reveals a novel regulatory mechanism underlying drug resistance and suggests that TRIB2 functions as a regulatory component of the PI3K network, activating AKT in cancer cells.

O objetivo deste trabalho foi avaliar a diversidade de plantas invasoras, em sistemas agroflorestais com cafeeiros (Coffea arabica L.) e em cafezal a pleno sol, sob manejo orgânico e convencional. Foram avaliados 20 tratamentos no delineamento de blocos ao acaso, em parcelas subdivididas no tempo, com três repetições. Os tratamentos corresponderam à combinação entre sistemas agroflorestais e quatro níveis de manejo, baseados na intensidade das práticas e aplicação de insumos: alto e médio convencional, médio e baixo orgânico. Em julho de 2002 e setembro de 2005 foi realizado o levantamento de plantas invasoras. Determinaram-se a riqueza, abundância, diversidade e eqüitabilidade. Observou-se redução nos valores médios de riqueza, abundância, diversidade e eqüitabilidade, em que os menores valores foram encontrados no tratamento com manejo alto convencional. Houve redução na freqüência das trepadeiras, ciperáceas e espécies de folhas estreitas (má cobertura), e aumento das espécies de folhas largas (boa cobertura) e gramíneas. Nas duas épocas, os maiores percentuais de pontos com solo descoberto foram encontrados no tratamento alto convencional, e os menores percentuais foram encontrados em todos os tratamentos com manejo médio e baixo orgânico, e em três dos sete tratamentos com manejo médio convencional. Tais resultados demonstram que onde há aplicação freqüente de herbicida, a presença de árvores não evita exposição do solo.

No abstract

The growth of diamond films in metastable condition occurs in two steps: nucleation and growth of crystals. Studies have shown that the nucleation process is the most critical step and essential to optimize the properties of the diamond, but its understanding is still very limited. Furthermore, the nucleation process is directly related to the pretreatment applied to the surface of the substrate: cleaning the surface and seeding. When the substrate is silicon, it is cleaned with acetone and scratching with diamond particles dispersed in a suitable solvent followed by ultrasonic agitation (nucleation rate = 109part/cm2). However, research has demonstrated that the use of diamond nanoparticles (ND) prepared with the use of a powerful ultrasound (750W) provides nucleation density much higher (1012part/cm2) compared to that processed with larger size particles. This work demonstrates that diamond films prepared with ND different solutions exhibit differences in relation to diamond films prepared using diamond particle dispersed in an organic solvent. Morphological analysis and the quality of the films were evaluated by Scanning Electron Microscopy, Optical Perfilometry and Raman Scattering Spectroscopy.