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Both the Linear Phenotypic Selection Index (LPSI) and the Restrictive Linear Phenotypic Selection Index (RLPSI) have been widely used to select parents and progenies, but the effect of economic weights on the selection parameters (the expected genetic gain, response to selection, and the correlation between the indices and genetic merits) have not been investigated in detail. Here, we (i) assessed combinations of 2304 economic weights using four traits (maturity, plant height, grain yield and grain protein content) recorded under four organically (low nitrogen) and five conventionally (high nitrogen) managed environments, (ii) compared single-trait and multi-trait selection indices (LPSI vs. RLPSI by imposing restrictions to the expected genetic gain of either yield or grain protein content), and (iii) selected a subset of about 10% spring wheat cultivars that performed very well under organic and/or conventional management systems. The multi-trait selection indices, with and without imposing restrictions, were superior to single trait selection. However, the selection parameters differed quite a lot depending on the economic weights, which suggests the need for optimizing the weights. Twenty-two of the 196 cultivars that showed superior performance under organic and/or conventional management systems were consistently selected using all five of the selected economic weights, and at least two of the selection scenarios. The selected cultivars belonged to the Canada Western Red Spring (16 cultivars), the Canada Northern Hard Red (3), and the Canada Prairie Spring Red (3), and required 83–93 days to maturity, were 72–100 cm tall, and produced from 4.0 to 6.2 t ha⁻¹ grain yield with 14.6–17.7% GPC. The selected cultivars would be highly useful, not only as potential trait donors for breeding under an organic management system, but also for other studies, including nitrogen use efficiency. Full article

Si306, a pyrazolo[3,4-d]pyrimidine derivative recently identified as promising anticancer agent, has shown favorable in vitro and in vivo activity profile against neuroblastoma (NB) models by acting as a competitive inhibitor of c-Src tyrosine kinase. Nevertheless, Si306 antitumor activity is associated with sub-optimal aqueous solubility, which might hinder its further development. Drug delivery systems were here developed with the aim to overcome this limitation, obtaining suitable formulations for more efficacious in vivo use. Si306 was encapsulated in pegylated stealth liposomes, undecorated or decorated with a monoclonal antibody able to specifically recognize and bind to the disialoganglioside GD2 expressed by NB cells (LP[Si306] and GD2-LP[Si306], respectively). Both liposomes possessed excellent morphological and physio-chemical properties, maintained over a period of two weeks. Compared to LP[Si306], GD2-LP[Si306] showed in vitro specific cellular targeting and increased cytotoxic activity against NB cell lines. After intravenous injection in healthy mice, pharmacokinetic profiles showed increased plasma exposure of Si306 when delivered by both liposomal formulations, compared to that obtained when Si306 was administered as free form. In vivo tumor homing and cytotoxic effectiveness of both liposomal formulations were finally tested in an orthotopic animal model of NB. Si306 tumor uptake resulted significantly higher when encapsulated in GD2-LP, compared to Si306, either free or encapsulated into untargeted LP. This, in turn, led to a significant increase in survival of mice treated with GD2-LP[Si306]. These results demonstrate a promising antitumor efficacy of Si306 encapsulated into GD2-targeted liposomes, supporting further therapeutic developments in pre-clinical trials and in the clinic for NB. Full article