Human midbrain precursors activate the expected developmental genetic program and differentiate long-term to functional A9 dopamine neurons in vitro. Enhancement by Bcl-XL

Understanding the molecular programs of the generation of human dopaminergic neurons (DAn) from their ventral mesencephalic (VM) precursors is of key importance for basic studies, progress in cell therapy, drug screening and pharmacology in the context of Parkinson's disease. The nature of human DAn precursors in vitro is poorly understood, their properties unstable, and their availability highly limited. Here we present positive evidence that human VM precursors retaining their genuine properties and long-term capacity to generate A9 type Substantia nigra human DAn (hVM1 model cell line) can be propagated in culture. During a one month differentiation, these cells activate all key genes needed to progress from pro-neural and prodopaminergic precursors to mature and functional DAn. For the first time, we demonstrate that gene cascades are correctly activated during differentiation, resulting in the generation of mature DAn. These DAn have morphological and functional properties undistinguishable from those generated by VM primary neuronal cultures. In addition, we have found that the forced expression of Bcl-XL induces an increase in the expression of key developmental genes (MSX1, NGN2), maintenance of PITX3 expression temporal profile, and also enhances genes involved in DAn long-term function, maintenance and survival (EN1, LMX1B, NURR1 and PITX3). As a result, Bcl-XL anticipates and enhances DAn generation.

Efficiency and environmental indexes to evaluate the sustainability of mineral and organic fertilization in an irrigated melon crop

Melon is traditionally cultivated in fertigated farmlands in the center of Spain with high inputs of water and N fertilizer. Excess N can have a negative impact, from the economic point of view, since it can diminish the production and quality of the fruit, from the environmental point of view, since it is a very mobile element in the soil and can contaminate groundwater. From health point of view, nitrate can be accumulated in fruit pulp, and, in addition, groundwater is the fundamental supply source of human populations. Best management practices are particularly necessary in this region as many zones have been declared vulnerable to NO3- pollution (Directive 91/676/CEE) During successive years, a melon crop (Cucumis melo L.) was grown under field conditions applying mineral and organic fertilizers under drip irrigation. Different doses of ammonium nitrate were used as well as compost derived from the wine-distillery industry which is relevant in this area. The present study reviews the most common N efficiency indexes under the different management options with a view to maximizing yield and minimizing N loss.