Bioenergetic Changes during Differentiation of Human Embryonic Stem Cells along the Hepatic Lineage.

Mitochondrial dysfunction has been demonstrated to result in premature aging due to its effects on stem cells. Nevertheless, a full understanding of the role of mitochondrial bioenergetics through differentiation is still lacking. Here we show the bioenergetics profile of human stem cells of embryonic origin differentiating along the hepatic lineage. Our study reveals especially the transition between hepatic specification and hepatic maturation as dependent on mitochondrial respiration and demonstrates that even though differentiating cells are primarily dependent on glycolysis until induction of hepatocyte maturation, oxidative phosphorylation is essential at all stages of differentiation

Peeling fingers in an elastic Hele-Shaw channel

Using experiments and a depth-averaged numerical model, we study instabilities of two-phase flows in a Hele-Shaw channel with an elastic upper boundary and a non-uniform cross-section prescribed by initial collapse. Experimentally, we find increasingly complex and unsteady modes of air-finger propagation as the dimensionless bubble speed, Ca, and level of collapse are increased, including pointed fingers, indented fingers and the feathered modes first identified by Cuttle et al.(J. Fluid Mech., vol. 886, 2020, A20). By introducing a measure of the viscous contribution to finger propagation, we identify a Ca threshold beyond which viscous forces are superseded by elastic effects. Quantitative prediction of this transition between 'viscous' and 'elastic' reopening regimes across levels of collapse establishes the fidelity of the numerical model. In the viscous regime, we recover the non-monotonic dependence on Ca of the finger pressure, which is characteristic of benchtop models of airway reopening. To explore the elastic regime numerically, we extend the depth-averaged model introduced by Fontana et al. (J. Fluid Mech., vol. 916, 2021, A27) to include an artificial disjoining pressure which prevents the unphysical self-intersection of the interface. Using time simulations, we capture for the first time the majority of experimental finger dynamics, including feathered modes. We show that these disordered states continually evolve, with no evidence of convergence to steady or periodic states. We find that the steady bifurcation structure satisfactorily predicts the bubble pressure as a function of Ca, but that it does not provide sufficient information to predict the transition to unsteady dynamics which appears strongly nonlinear.Comment: 28 pages, 15 figure

Fluctuations in viscous fingering

Our experiments on viscous (Saffman-Taylor) fingering in Hele-Shaw channels reveal finger width fluctuations that were not observed in previous experiments, which had lower aspect ratios and higher capillary numbers Ca. These fluctuations intermittently narrow the finger from its expected width. The magnitude of these fluctuations is described by a power law, Ca^{-0.64}, which holds for all aspect ratios studied up to the onset of tip instabilities. Further, for large aspect ratios, the mean finger width exhibits a maximum as Ca is decreased instead of the predicted monotonic increase.Comment: Revised introduction, smoothed transitions in paper body, and added a few additional minor results. (Figures unchanged.) 4 pages, 3 figures. Submitted to PRE Rapi

Effect of therapeutic plasma exchange on immunoglobulins in myasthenia gravis

An integrated understanding of therapeutic plasma exchange (TPE) effects on immunoglobulins, autoantibodies, and natural or acquired (vaccine) protective antibodies in patients with autoimmune myasthenia gravis (MG) is lacking. Prior studies measured TPE effects in healthy volunteers or heterogeneous autoimmune diseases populations. We prospectively profiled plasma IgA, IgM, IgG, IgG subclasses (IgG1-4), acetylcholine receptor autoantibodies (AChR+), and protective antibodies in patients with AChR+ MG receiving TPE for an exacerbation. TPE was performed according to institutional practice and patients were profiled for up to 12 weeks. Ten patients were enrolled (median age=72.9 years; baseline MG-Composite=21; median TPE treatments=6 during their first course) and all improved. The maximum decrease in all immunoglobulins, including AChR autoantibodies, was achieved on the final day of the first TPE course (approximately 60–70% reduction). Three weeks post-TPE mean AChR autoantibody, total IgG, IgG1 and IgG2 titers were below the reference range and had not recovered to within 20% of baseline, whereas other measured immunoglobulins approached baseline values. We did not generally observe an “overshoot” of immunoglobulins above pre-TPE levels or accelerated recovery of pathologic AChR autoantibodies. Protective antibody profiles showed similar patterns as other IgGs and were detectable at levels associated with protection from infection. A slow return to baseline for IgGs (except IgG3) was observed, and we did not observe any obvious effect of concomitant medications on this recovery. Collectively, these findings enhance our understanding of the immunological effects of TPE and further supports the concept of rapid immunoglobulin depletion for the treatment of patients with MG

Inspiratory muscle training reduces blood lactate concentration during volitional hyperpnoea

Although reduced blood lactate concentrations ([lac−]B) have been observed during whole-body exercise following inspiratory muscle training (IMT), it remains unknown whether the inspiratory muscles are the source of at least part of this reduction. To investigate this, we tested the hypothesis that IMT would attenuate the increase in [lac−]B caused by mimicking, at rest, the breathing pattern observed during high-intensity exercise. Twenty-two physically active males were matched for 85% maximal exercise minute ventilation (V˙Emax) and divided equally into an IMT or a control group. Prior to and following a 6 week intervention, participants performed 10 min of volitional hyperpnoea at the breathing pattern commensurate with 85% V˙Emax