Neonatal umbilical cord blood transplantation halts skeletal disease progression in the murine model of MPS-I

Umbilical cord blood (UCB) is a promising source of stem cells to use in early haematopoietic stem cell transplantation (HSCT) approaches for several genetic diseases that can be diagnosed at birth. Mucopolysaccharidosis type I (MPS-I) is a progressive multi-system disorder caused by deficiency of lysosomal enzyme α-L-iduronidase, and patients treated with allogeneic HSCT at the onset have improved outcome, suggesting to administer such therapy as early as possible. Given that the best characterized MPS-I murine model is an immunocompetent mouse, we here developed a transplantation system based on murine UCB. With the final aim of testing the therapeutic efficacy of UCB in MPS-I mice transplanted at birth, we first defined the features of murine UCB cells and demonstrated that they are capable of multi-lineage haematopoietic repopulation of myeloablated adult mice similarly to bone marrow cells. We then assessed the effectiveness of murine UCB cells transplantation in busulfan-conditioned newborn MPS-I mice. Twenty weeks after treatment, iduronidase activity was increased in visceral organs of MPS-I animals, glycosaminoglycans storage was reduced, and skeletal phenotype was ameliorated. This study explores a potential therapy for MPS-I at a very early stage in life and represents a novel model to test UCB-based transplantation approaches for various diseases

Large-Eddy Simulation of Turbulent Flames in Syn-Gas Fuel-Air Mixtures

Combustion characteristics of synthetic gaseous fuels (H2 and CO mixture) have been investigated in laminar and turbulent flow congurations with special emphasis on flame structure and propagation characteristics of CO-rich and H2-rich premixed flames. Two reduced CO H2 mechanisms (10-step and 5-step) are first investigated and it is shown that the 10-step mechanism is quite accurate over a wide range of equivalence ratios and with and without CO2 dilution. The 10-step mechanism is then used for both laminar and turbulent premixed flame calculations of both CO-rich and H2-rich mixtures. The effect of a single isolated vortex interacting with a laminar flame and of a pair of counter rotating vortices with a turbulent premixed \ud flame front are investigated for different turbulence levels. It is shown that H2 reaction zone is much thinner than the CO reaction zone, and that they do not overlap physically. Under certain conditions, the H2 reaction rate contours can become broken even when the CO reaction rate contours remains contiguous. Flame structure and propagation (burning) speed are substantially different depending upon the syn-gas (COH2) composition. Flame-vortex interaction creates large-scale flame wrinkling, the scale of which also depends on the initial fuel composition. Flame-vortex interactions also causes local enhancement and dissipation of vorticity depending on the local baroclinic torque and dilatation effects

Synthetic biology to access and expand nature's chemical diversity

Bacterial genomes encode the biosynthetic potential to produce hundreds of thousands of complex molecules with diverse applications, from medicine to agriculture and materials. Accessing these natural products promises to reinvigorate drug discovery pipelines and provide novel routes to synthesize complex chemicals. The pathways leading to the production of these molecules often comprise dozens of genes spanning large areas of the genome and are controlled by complex regulatory networks with some of the most interesting molecules being produced by non-model organisms. In this Review, we discuss how advances in synthetic biology — including novel DNA construction technologies, the use of genetic parts for the precise control of expression and for synthetic regulatory circuits — and multiplexed genome engineering can be used to optimize the design and synthesis of pathways that produce natural products