Transcranial magnetic stimulation as a translational biomarker for AMPA receptor modulation

TAK-653 is a novel alpha -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-positive allosteric modulator being developed as a potential therapeutic for major depressive disorder (MDD). Currently, there are no translational biomarkers that evaluate physiological responses to the activation of glutamatergic brain circuits available. Here, we tested whether noninvasive neurostimulation, specifically single-pulse or paired-pulse motor cortex transcranial magnetic stimulation (spTMS and ppTMS, respectively), coupled with measures of evoked motor response captures the pharmacodynamic effects of TAK-653 in rats and healthy humans. In the rat study, five escalating TAK-653 doses (0.1-50mg/kg) or vehicle were administered to 31 adult male rats, while measures of cortical excitability were obtained by spTMS coupled with mechanomyography. Twenty additional rats were used to measure brain and plasma TAK-653 concentrations. The human study was conducted in 24 healthy volunteers (23 males, 1 female) to assess the impact on cortical excitability of 0.5 and 6mg TAK-653 compared with placebo, measured by spTMS and ppTMS coupled with electromyography in a double-blind crossover design. Plasma TAK-653 levels were also measured. TAK-653 increased both the mechanomyographic response to spTMS in rats and the amplitude of motor-evoked potentials in humans at doses yielding similar plasma concentrations. TAK-653 did not affect resting motor threshold or paired-pulse responses in humans. This is the first report of a translational functional biomarker for AMPA receptor potentiation and indicates that TMS may be a useful translational platform to assess the pharmacodynamic profile of glutamate receptor modulators.Stress-related psychiatric disorders across the life spa

Avaliação da incidência de antracnose, do desempenho e estado nutricional de variedades de mangueira, para cultivo orgânico, na região centro-norte do Estado de São Paulo.

A mudança do perfil do consumidor, aliada aos riscos da contaminação por agrotóxicos, tem levado à busca de alternativas ecologicamente apropriadas para produção de frutas. Os objetivos deste trabalho foram avaliar a incidência de antracnose, o desempenho e estado nutricional de variedades de mangueira conduzidas organicamente na região de Pindorama-SP. Foram utilizadas 17 variedades de mangueira. O experimento foi instalado em delineamento experimental em blocos completos ao acaso, com 17 tratamentos (variedades) e seis repetições. Foi avaliada a severidade de antracnose nas folhas, através de uma escala diagramática, atribuindo-se notas aos sintomas. Foram avaliados o crescimento e o desenvolvimento (altura da planta, perímetro do tronco e da copa) e o estado nutricional, mediante análise foliar, das diferentes variedades utilizadas. Através dos resultados obtidos, podem-se considerar como muito suscetíveis à antracnose as variedades Bourbon, Rocha e Rosa; e resistentes, as variedades IAC 111, Alfa, Beta e Parvin; as variedades de manga apresentaram o mesmo padrão de crescimento; as maiores alturas da planta corresponderam aos maiores diâmetros do tronco e da copa; a variedade Parvin apresentou o melhor desempenho dentre as variedades estudadas, com relação à resistência à antracnose, altura e diâmetro do caule e da copa, podendo ser recomendada ao cultivo orgânico. As variedades Omega e Alfa também apresentaram bom crescimento, podendo ser indicadas para esse cultivo, pelo menos nessa fase inicial; as variedades Surpresa e Rosa não apresentaram bom desempenho, no campo, em relação às demais, não devendo ser recomendadas para o cultivo orgânico, principalmente a variedade Rosa, bastante suscetível à antracnose. As concentrações de N, P e K foram elevadas na fase vegetativa das plantas, comparadas à baixa concentração de Ca; houve carência de Boro em todas as variedades estudadas. A manga Rosa, provavelmente, sofreu toxicidade ao excesso de manganês, ocasionando diminuição em seu desenvolvimento

Susceptibility to prosocial and antisocial influence in adolescence

INTRODUCTION: Adolescents are particularly susceptible to social influence and previous studies have shown that this susceptibility decreases with age. The current study used a cross-sectional experimental paradigm to investigate the effect of age and puberty on susceptibility to both prosocial and antisocial influence. METHODS: Participants (N = 520) aged 11-18 from London and Cambridge (United Kingdom) rated how likely they would be to engage in a prosocial (e.g. "help a classmate with their work") or antisocial (e.g. "make fun of a classmate") act. They were then shown the average rating (in fact fictitious) that other adolescents had given to the same question, and were then asked to rate the same behaviour again. RESULTS: Both prosocial and antisocial influence decreased linearly with age, with younger adolescents being more socially influenced when other adolescents' ratings were more prosocial and less antisocial than their own initial rating. Both antisocial and prosocial influence significantly decreased across puberty for boys but not girls (independent of age). CONCLUSIONS: These findings suggest that social influence declines with increasing maturity across adolescence. However, the exact relationship between social influence and maturity is dependent on the nature of the social influence and gender. Understanding when adolescents are most susceptible to different types of social influence, and how this might influence their social behaviour, has important implications for understanding adolescent social development