Obesity is a major risk factor for developing metabolic complications, such as diabetes. Regular exercise is an effective way to retain a healthy body weight and improve metabolic disorders. Recently, Boström P. et al. has characterized a novel hormone named by him as irisin, which is released by the exercising muscle and promotes energy expenditure in mice, via increased thermogenesis, a well recognized effect of regular exercise. Irisin achieves this effect by promoting the formation of mitochondria rich, brown-fat like cells (beige cells) in subcutaneous fat depots. In addition, adenoviral delivery of irisin to mice protected them against high fat diet induced diabetes II and obesity. Given its proven powerful antidiabetic properties irisin may be an effective future treatment against diabetes and obesity. In addition it is 100% conserved between human and mouse, and it is increased in the human plasma after exercise.In the present research proposal, we plan to identify the receptor of Irisin using the well established method of expression cloning. Furthermore, we will do therapeutic testing of exogenous forms of Irisin, delivered intraperitoneally as FC-contructs to mice fed a high fat diet. Given success we will have developed a powerful drug, ready for phase I clinical trial.

Mathematical abilities are important for educational and professional success. Previous research has identified nonverbal reasoning abilities as predictive of mathematical abilities, and thus a possible target of training to improve mathematical performance. However, the specificity of the relation between different forms of nonverbal reasoning (i.e. relational and logical) and different forms of mathematical abilities (i.e. arithmetic, algebra, geometry) is currently unknown. Therefore, the goal of the proposed research is to examine the specificity of the relation between nonverbal reasoning and mathematics on the behavioral and neural level, in order to identity the best predictors of mathematical abilities and the best targets of training to improve these abilities. To achieve this goal, we propose to: 1) perform a large scale behavioral study in which relational and logical nonverbal reasoning will be linked to different types of mathematical abilities (arithmetics, algebra, geometry) in adolescents; 2) use the state-of-the-art visuotopic mapping of the parietal cortex using functional MRI to make a fine-grained assessment of the commonalties and differences in neural basis of different forms of nonverbal reasoning and mathematical abilities; and 3) examine how nonverbal reasoning training changes nonverbal reasoning and mathematical performance and brain activity and structure in adolescents.

NANOSPRESSO-NL specifically addresses the current mismatch between personalized therapeutic strategies and industrial centralized large-scale manufacture of medicines. The NANOSPRESSO-NL consortium is convinced that nucleic acid therapeutics are uniquely qualified for production in local hospital pharmacies in response to the needs of the individual patient. By switching towards a fully standardised platform formulation, quality control can be centred around the production process rather than the end product, quite similar to a popular method of decentralized high-quality espresso making.