Advancing schizophrenia drug discovery : optimizing rodent models to bridge the translational gap

Although our knowledge of the pathophysiology of schizophrenia has increased, treatments for this devastating illness remain inadequate. Here, we critically assess rodent models and behavioural end points used in schizophrenia drug discovery and discuss why these have not led to improved treatments. We provide a perspective on how new models, based on recent advances in the understanding of the genetics and neural circuitry underlying schizophrenia, can bridge the translational gap and lead to the development of more effective drugs. We conclude that previous serendipitous approaches should be replaced with rational strategies for drug discovery in integrated preclinical and clinical programmes. Validation of drug targets in disease-based models that are integrated with translationally relevant end point assessments will reduce the current attrition rate in schizophrenia drug discovery and ultimately lead to therapies that tackle the disease process

Tooth Bleaching Increases Dentinal Protease Activity

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Hydrogen peroxide is an oxidative agent commonly used for dental bleaching procedures. The structural and biochemical responses of enamel, dentin, and pulp tissues to the in vivo bleaching of human (n = 20) premolars were investigated in this study. Atomic force microscopy (AFM) was used to observe enamel nanostructure. The chemical composition of enamel and dentin was analyzed by infrared spectroscopy (FTIR). The enzymatic activities of dental cathepsin B and matrix metalloproteinases (MMPs) were monitored with fluorogenic substrates. The amount of collagen in dentin was measured by emission of collagen autofluorescence with confocal fluorescence microscopy. The presence of Reactive Oxygen Species (ROS) in the pulp was evaluated with a fluorogenic 2',7'-dichlorodihydrofluorescein diacetate (DCFDA) probe. Vital bleaching of teeth significantly altered all tested parameters: AFM images revealed a corrosion of surface enamel nanostructure; FTIR analysis showed a loss of carbonate and proteins from enamel and dentin, along with an increase in the proteolytic activity of cathepsin-B and MMPs; and there was a reduction in the autofluorescence of collagen and an increase in both cathepsin-B activity and ROS in pulp tissues. Together, these results indicate that 35% hydrogen peroxide used in clinical bleaching protocols dramatically alters the structural and biochemical properties of dental hard and soft pulp tissue.922187192Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)NIDCR [DE 015306]Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)NIDCR [DE 015306

Pair suppression caused by mosaic-twist defects in superconducting Sr<inf>2</inf>RuO<inf>4</inf> thin-films prepared using pulsed laser deposition

Sr2RuO4 is a prototypical unconventional superconductor, but the superconducting symmetries of the bulk and surface states in single crystals remains controversial. Solving this problem is impeded by the challenge of producing thin-films of Sr2RuO4 free of defects and impurities which annihilate the superconductivity. Here, we report the reliable growth of superconducting Sr2RuO4 thin-films by pulsed laser deposition and identify the universal material properties that are destructive to the superconducting state. We demonstrate that careful control of the starting material is essential to achieve superconductivity as well as the use of a single crystal target of Sr3Ru2O7. By systematically varying the Sr2RuO4 film thickness, we identify mosaic twist as the key in-plane defect that suppresses superconductivity. These results are central to the development of our understanding of unconventional superconductivity

Análises técnicas e econômicas no sistema de integração lavoura-pecuária submetido à adubação nitrogenada

Sustentabilidade agropecuária, redução nos custos de produção e agregação de valor ao sistema agrícola são alcançadas pelo uso das áreas durante todo o ano em sistemas integrados ou consorciados de produção. Este trabalho teve como objetivos determinar a matriz de coeficientes técnicos e estimar e avaliar o custo operacional total (COT) e os indicadores de lucratividade (IL) do consórcio do milho com duas espécies do gênero Brachiaria (B. brizantha cv, MG-5 e B. ruziziensis), submetidas a doses de N (0, 100, 200, 300 e 400 kg ha-1 ano-1) em cobertura, utilizando-se como fonte a ureia, e do feijoeiro de inverno em sucessão, na Integração Lavoura-Pecuária (ILP) em sistema plantio direto (SPD), no ano agrícola de 2008/2009, em condições irrigadas no Cerrado. O experimento foi instalado em delineamento experimental em blocos casualizados, com quatro repetições, em esquema fatorial 2 x 5. Os insumos foram os componentes que mais oneraram o custo de produção do milho e feijão na ILP estudada. O COT aumentou de forma diretamente proporcional às doses de N em cobertura. Para todos os tratamentos os índices de lucratividade (IL) foram positivos, indicando a viabilidade da modalidade. O tratamento que apresentou melhores desempenhos técnico e econômico foi o milho em consórcio com B. brizantha, adubados com 100 kg ha-1ano-1 de N e feijão em sucessão