Quantifying membrane permeability of amphotericin B ion channels in single living cells.

Recently, the structure-function relationships between amphotericin B (AmB) and ergosterol have been solved using synthetic techniques that require a mycosamine-mediated direct binding interaction between AmB and ergosterol to form AmB ion channels. However, studies to directly probe the AmB-induced membrane permeability changes have not been conducted. In the present work, we investigate the following fundamental question: does AmB induce concentration- and time-dependent permeability changes across ergosterol-containing membranes? Herein, we employ fluorescent dyes of known average diameter to quantify the diameters of AmB ion channels. In addition, we take a single-particle tracking approach to define the intracellular microrheology in the absence and presence of AmB ion channels. Present results show that increasing AmB concentration tends to increase the preferential accumulation of AmB ion channels in the presence of the excess membrane-embedded ergosterol. We found that AmB induces time-dependent membrane permeability; increases approaching 50% in both the velocity fluctuations and diffusion coefficients of vesicles occur on the same time scale as the efflux of potassium ions (≅30min). Furthermore, we propose a two-dimensional, semi-regular tessellation model to geometrically assess the pore size of the AmB ion channels in response to the AmB dose. This approach offers one possibility for the design of AmB ion channels with tunable aqueous pore size, which could provide an opportunity to replace damaged membrane water channels of the aquaporin family in future applications.

Effects of Exergame-Based Dual-Task Training on Executive Function and Dual-Task Performance in Community-Dwelling Older People: A Randomized-Controlled Trial.

Objective: Aging is associated with decline in executive function that may lead to reduced dual-task performance. Regular exercise has been recommended for promoting or maintaining mental and physical health in older adults, yet only a fraction of older adults exercise regularly. Exergame training may have the potential to enhance exercise adherence. Therefore, the aim of this study was to examine the effects of exergame-based dual-task training on executive function and dual-task performance in community-dwelling older adults. Materials and Methods: This was a single-blinded, randomized-controlled trial. Twenty community-dwelling older adults were recruited and randomly assigned to one of two groups. All participants completed 36 trainings, including three 60-minute sessions/week over 12 weeks. Participants in the experimental group received exergame-based dual-task training, while those in the control group received home-based multicomponent exercise training. Measures of executive function, dual-task performance, and community walking ability were assessed before and after the intervention. Results: Significant group × time interactions (P = 0.000-0.027) with large effects were found in all selected outcome measures. Compared with the control group, the experimental group improved significantly in measures of general executive function (P = 0.014), inhibitory control (P = 0.037), cognitive dual-task performance (P < 0.001), and community walking ability (P = 0.002). Enhanced general executive function was highly correlated with either improved motor dual-task performance (r = 0.674) or improved cognitive dual-task performance (r = -0.701). Conclusion: These results suggested that exergame-based dual-task training improved both executive function and dual-task performance in older people. These positive effects could be transferred to enhance community walking ability. Clinical Trial Registration number: ACTRN 12617000095369.