Falcipains, Plasmodium falciparum Cysteine Proteases as Key Drug Targets Against Malaria

There is a high demand for new drugs against malaria, which takes millions of lives annually. The abuse of classical antimalarials from the late 1940's to the early 1980's has bred resistant parasites, which led to the use of more potent drugs that ended up by refueling the resistance cycle. An example is chloroquine, once highly effective but now virtually useless against malaria. Structure-based rational drug design relies on high-resolution target structures to allow for screening of selective ligands/inhibitors. For the past two decades, and especially after the unveiling of the Plasmodium falciparum genome in 2002, enzymes of this lethal malaria parasite species have been increasingly attracting the attention of Medicinal Chemists worldwide as promising drug targets. There is particular emphasis on proteases having key roles on the degradation of host's hemoglobin within the food vacuole of blood-stage parasites, as these depend on such process for their survival. Among such enzymes, Plasmepsins (aspartic proteases) and, especially, Falcipains (cysteine proteases) are highly promising antimalarial drug targets. The present review will focus on the computational approaches made so far towards the unraveling of the structure, function and inhibition of Falcipains that, by virtue of their quite specific features, are excellent targets for highly selective inhibitors

Ações de saúde mental no Programa Saúde da Família: confluências e dissonâncias das práticas com os princípios das reformas psiquiátrica e sanitária Mental health care in the Family Health Program: consensus and dissent in practices and principles under the psychiatric reform and health reform in Brazil

Em um grande número de Reformas Psiquiátricas que se sedimentam sobre os pressupostos básicos da não-institucionalização dos pacientes psiquiátricos e da consolidação de bases territoriais do cuidado em saúde mental, a ênfase é atribuída a uma rede de cuidados que contemple a rede de atenção primária. No Brasil, a Reforma Psiquiátrica Brasileira nasce no bojo da Reforma Sanitária, guardando em comum princípios que reorientariam o modelo de atenção. Neste artigo, discutiremos as articulações entre esses dois movimentos por intermédio das práticas concretas do cuidado de saúde mental no Programa Saúde da Família (PSF), tomando como base um estudo etnográfico com quatro equipes de saúde da família, em que priorizamos a narrativa dos trabalhadores de saúde. Analisaremos, dessas práticas, discrepâncias entre o proposto normativo e o instituído, fatores dificultadores e conquistas da operacionalização das ações e limites da confrontação e potencialidades da transversalidade de campos epistemológicos particulares como a clínica ampliada da saúde mental e do PSF. Moveremos nossa discussão com base em conceitos como modelo psicossocial do cuidado, integralidade da atenção, participação social, territorialidade, ações coletivas, entre outros.<br>In many psychiatric reforms based on the principles of deinstitutionalization of psychiatric patients and the consolidation of territorial systems for mental health care, the emphasis is on a mental health care system that includes the primary care network. In Brazil, the Psychiatric Reform emerged within the country's overall Health Reform, with which it shares common principles for reorienting the model of care. The current article discusses the links between these two movements through actual mental health care practices within the Family Health Program (FHP), based on an ethnographic study with four family health teams, in which the authors prioritize health workers' narratives. The article analyzes these practices, the discrepancies between guidelines and practice, obstacles and advances in the operationalization of activities, and limits to the comparison and potentialities for cross-cutting application of particular epistemological fields like expanded clinical mental health practice and the FHP. The discussion is based on such concepts as the psychosocial care model, comprehensive care, social participation, territoriality, and collective actions

Genetic variation in growth traits and yield of rubber trees (Hevea brasiliensis) growing in the Brazilian state of São Paulo

Analysis of variance and covariance was preformed on growth traits (stem girth, bark thickness, total height gain and rubber yield) of 22 open-pollinated progenies of the rubber tree Hevea brasiliensis from an Asian Hevea collection introduced to Agronomic Institute (Instituto Agronômico, Campinas, São Paulo, Brazil; IAC) in 1952. This progeny trial was replicated at three sites in São Paulo state and it was found that at three years from sowing there was statistically significant variation for girth, bark thickness, height and rubber yield. An individual test sites, values of individual plant heritability for girth ranged from h= 0.36 to h= 0.89 whereas values for heritability for progeny means ranged from h= 0.77 to h= 0.87. These moderate and high heritabilities suggest that a combination of progeny and within-progeny selection would be effective at increasing girth in this population at individual sites. Across sites, values of individual-plant heritability for girth ranged from h= 0.36 to h= 0.47, whereas values for heritability of progeny means girth ranged from h= 0.77 to h= 0.87. There were high positive genetic correlations between increased girth and bark thickness suggesting that breeding aimed at increasing girth would also increase bark thickness and possibly height