Herein, we investigate the impact of metabolic stress as a result of inefficient feeding utilizing a novel perfusion bioreactor and a mathematical model to achieve bioprocess improvement. Methodology/Principal Findings: To characterize nutritional requirements, the expansion of undifferentiated murine ESCs (mESCs) encapsulated in hydrogels was performed in batch and perfusion cultures using bioreactors. Despite sufficient nutrient and growth factor provision, the accumulation of inhibitory metabolites resulted in the unscheduled differentiation of mESCs and a decline in their cell numbers in the

batch cultures. Nutlin-3 price In contrast, perfusion cultures maintained metabolite concentration below toxic levels, resulting in the robust expansion ( bigger than 16-fold) of high quality ‘naive’ mESCs within 4 days. A multi-scale mathematical model describing population segregated growth kinetics, metabolism and the expression of selected pluripotency (stemness) genes was implemented to maximize information from available experimental data. A global sensitivity analysis (GSA) was employed that identified significant (6/29) model parameters and enabled model validation. Predicting

the preferential propagation of undifferentiated ESCs in perfusion culture conditions demonstrates synchrony between theory and experiment. Conclusions/Significance: The limitations of batch culture highlight the importance of cellular metabolism in maintaining pluripotency, which necessitates the design of suitable ESC bioprocesses. We propose a novel investigational framework that integrates Selleckchem LB-100 a novel perfusion culture platform (controlled metabolic conditions) with mathematical modeling (information maximization) to enhance ESC bioprocess

productivity and facilitate bioprocess optimization.”
“The purpose of the study was to describe a pedigree with NEFL E396K mutation associated with a novel dominant intermediate Charcot-Marie-Tooth disease (DI-CMT) phenotype. The pedigree comprised four patients over two generations, aged between 35 and 59 years, who have been serially evaluated since Selleckchem HDAC inhibitor 1993. Their clinical picture was characterized by pes cavus, sensorimotor neuropathy and spastic gait. Both older patients showed ascending leg weakness to involve pelvic musculature. CMT neuropathy score ranged from 14 to 26 (moderate to severe disease). Electrophysiology showed uniform nerve conduction slowing in the intermediate range, both in distal and proximal nerve segments. Multimodal evoked potential and blink reflex studies revealed abnormalities indicative of central sensorimotor pathway dysfunction. On imaging studies of lower-limb musculature, there was massive atrophy of intrinsic foot muscles and to a lesser degree of calves and thighs predominating in muscles innervated by tibial and sciatic nerves.