Resistance to nucleoside analog reverse transcriptase inhibitors mediated by human immunodeficiency virus type 1 p6 protein.

Resistance of human immunodeficiency virus type 1 (HIV-1) to antiretroviral agents results from target gene mutation within the pol gene, which encodes the viral protease, reverse transcriptase (RT), and integrase. We speculated that mutations in genes other that the drug target could lead to drug resistance. For this purpose, the p1-p6(gag)-p6(pol) region of HIV-1, placed immediately upstream of pol, was analyzed. This region has the potential to alter Pol through frameshift regulation (p1), through improved packaging of viral enzymes (p6(Gag)), or by changes in activation of the viral protease (p6(Pol)). Duplication of the proline-rich p6(Gag) PTAP motif, necessary for late viral cycle activities, was identified in plasma virus from 47 of 222 (21.2%) patients treated with nucleoside analog RT inhibitor (NRTI) antiretroviral therapy but was identified very rarely from drug-naïve individuals. Molecular clones carrying a 3-amino-acid duplication, APPAPP (transframe duplication SPTSPT in p6(Pol)), displayed a delay in protein maturation; however, they packaged a 34% excess of RT and exhibited a marked competitive growth advantage in the presence of NRTIs. This phenotype is reminiscent of the inoculum effect described in bacteriology, where a larger input, or a greater infectivity of an organism with a wild-type antimicrobial target, leads to escape from drug pressure and a higher MIC in vitro. Though the mechanism by which the PTAP region participates in viral maturation is not known, duplication of this proline-rich motif could improve assembly and packaging at membrane locations, resulting in the observed phenotype of increased infectivity and drug resistance.

Risk assessment of herbicide mixtures in a large European lake

Lake Geneva is one of the largest European lakes with a surface area of 580 km2. Its catchment area covers 7400 km2, of which approximately 20% is arable land. Monitoring campaigns have been carried out in 2004 and 2005 to determine the contamination of the lake by pesticides. The results highlight the widespread presence of herbicides in water, the measured concentrations for most substances remaining constant in 2004 and 2005. However, for some individual herbicides the concentrations increased drastically (e.g., the herbicide foramsulfuron). We assessed the environmental risk of the herbicides detected in the lake using water quality criteria recently determined for the Swiss environmental protection agency. Furthermore, we assessed the risk of herbicide mixtures, grouped based upon their mode of action. Generally, the risk estimated for all single substances is low, except for some sulfonylurea compounds. For these substances, the measured concentrations are higher than the predicted no-effect concentration. Impact on the flora of the lake can therefore not be excluded. When mixtures of pesticides with similar mode of action are taken into account, the risk remains lower than the mixture water quality criteria for all groups, but can reach as high as one third of this quality criteria. A further step would therefore be to assess the risk of the total pesticide mixture, including similar and dissimilar modes of action

Avaliação de desempenho e Motivação:O impacto das Recompensas na Motivação e obtenção de Melhorias de Desempenho O Caso da Transcor SV, S.A.

A realização do presente estudo tem por intuito analisar o impacto das recompensas na motivação e obtenção de melhorias de desempenho. O estudo de caso inerente a este documento recaiu sobre uma empresa de transportes rodoviários de passageiros de Cabo Verde, a “Transcor SV, S.A.”. Os resultados acusaram que neste contexto organizacional, os trabalhadores do escritório e os controladores atribuem um impacto positivo às recompensas na motivação e obtenção de melhorias de desempenho, tendo sido apurado que para além das recompensas deve-se ter em linha de conta outras medidas para promover efectivamente a motivação. Verificou-se que qualquer quantia monetária utilizada para recompensar o bom desempenho é significativa para causar a motivação para melhores desempenhos. Existindo uma grande confiança por parte dos trabalhadores em relação à gestão, a recompensa atribuída (num contexto em que os resultados relativos ao desempenho acorreram de uma avaliação de desempenho justa) fomenta a motivação. Este estudo também demonstrou que as recompensas aumentam a motivação extrínseca e que, nos casos em que o trabalhador é avesso a desafios, consegue diminuir a motivação intrínseca, quando o contexto em que o trabalhador encontra-se inserido é desfavorável (não foi contemplado na atribuição da recompensa).

[Chicago] 18/8 -32

Kirje 18.8.1932