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.

Social companies as an innovative and sustainable way of solving social problems. A case study from Spain.

In the current context of economic crisis, there is an increasing need for new approaches for solving social problems without relying upon public resources. With this regard, social entrepreneurship has been arising as an important solution to develop social innovations and address social needs. Social entrepreneurs found new ventures that aim at solving social problems. The main purpose of this research is to identify the general profile of the social entrepreneurs and the main features of social companies, such as geographic scope, profit or non-profit approach, collaborative networks, decision making structure, and typologies of customers that benefit from their social actions.

Characterising social media users by gender and place of residence

Characterising users through demographic attributes is a necessary step before conducting opinion surveys from information published by such users in social media. In this paper, we describe, compare and evaluate different techniques for the identification of the attributes "gender"' and "place of residence" by mining the metadata associated to the users, the content published and shared by themselves, and their friendship networks. The results obtained show that the social network is a valuable source of information for obtaining the sociodemographic attributes of single users.