Generation of a High Number of Healthy Erythroid Cells from Gene-Edited Pyruvate Kinase Deficiency Patient-Specific Induced Pluripotent Stem Cells

Pyruvate kinase deficiency (PKD) is a rare erythroid metabolic disease caused by mutations in the PKLR gene. Erythrocytes from PKD patients show an energetic imbalance causing chronic non-spherocytic hemolytic anemia, as pyruvate kinase defects impair ATP production in erythrocytes. We generated PKD induced pluripotent stem cells (PKDiPSCs) from peripheral blood mononuclear cells (PB-MNCs) of PKD patients by non-integrative Sendai viral vectors. PKDiPSCs were gene edited to integrate a partial codon-optimized R-type pyruvate kinase cDNA in the second intron of the PKLR gene by TALEN-mediated homologous recombination (HR). Notably, we found allele specificity of HR led by the presence of a single-nucleotide polymorphism. High numbers of erythroid cells derived from gene-edited PKDiPSCs showed correction of the energetic imbalance, providing an approach to correct metabolic erythroid diseases and demonstrating the practicality of this approach to generate the large cell numbers required for comprehensive biochemical and metabolic erythroid analyses.info:eu-repo/semantics/publishedVersio

Infrastructures and tools for multiagent systems for the new generation of distributed systems

In order for multiagent systems to be included in real domains (media and Internet, logistics, e-commerce, and health care), infrastructures and tools for multiagent systems should provide efficiency, scalability, security, management, monitoring, and other features related to building real applications. Thus, infrastructures and tools that support multiagent systems are needed, especially those that promote the adoption of agent-based systems by designers and programmers in both academia and industry. This special issue is a selection of contributions whose preliminary versions were presented at the ITMAS 2010 workshop, which was held in conjunction with the International Conference on Autonomous Agents and Multi-agent SystemsGarcía-Fornes, A.; Hübner, JF.; Omicini, A.; Rodríguez-Aguilar, JA.; Botti Navarro, VJ. (2011). Infrastructures and tools for multiagent systems for the new generation of distributed systems. Engineering Applications of Artificial Intelligence. 24(7):1095-1097. doi:10.1016/j.engappai.2011.06.012S1095109724