GJA1 depletion causes ciliary defects by affecting Rab11 trafficking to the ciliary base.

The gap junction complex functions as a transport channel across the membrane. Among gap junction subunits, gap junction protein α1 (GJA1) is the most commonly expressed subunit. A recent study showed that GJA1 is necessary for the maintenance of motile cilia; however, the molecular mechanism and function of GJA1 in ciliogenesis remain unknown. Here, we examined the functions of GJA1 during ciliogenesis in human retinal pigment epithelium-1 and Xenopus laevis embryonic multiciliated-cells. GJA1 localizes to the motile ciliary axonemes or pericentriolar regions beneath the primary cilium. GJA1 depletion caused malformation of both the primary cilium and motile cilia. Further study revealed that GJA1 depletion affected several ciliary proteins such as BBS4, CP110, and Rab11 in the pericentriolar region and basal body. Interestingly, CP110 removal from the mother centriole was significantly reduced by GJA1 depletion. Importantly, Rab11, a key regulator during ciliogenesis, was immunoprecipitated with GJA1 and GJA1 knockdown caused the mislocalization of Rab11. These findings suggest that GJA1 regulates ciliogenesis by interacting with the Rab11-Rab8 ciliary trafficking pathway.

Estimation of saline-mixed tissue conductivity and ablation lesion size.

In radiofrequency ablation (RFA), saline infusion is beneficial for enhancing electrical conductivity, which allows more energy dissipation into target tissue, resulting in increased lesion size. Computational simulation has been a popular method to estimate lesion size from RFA treatment, but it has not been used effectively for saline-infused RFA, for lack of methods to address the conductivity properties of saline-tissue mixtures. To fill this gap, we propose a microscopic mixture model to derive the effective temperature-dependent conductivities of a saline-tissue mixture. We modeled a small block of 6% hypertonic saline-infused liver tissue as a 1 × 1 × 1 cm cube, which was divided into 64-1000 elements, with each element representing either liver tissue or saline. A 1:1 mixing of saline and liver tissue was assumed to calculate the effective conductivities at 30, 50, 70, and 90°C. Different mixing conditions (2:1 and 1:2 of saline to liver tissue) were also tested to observe the effect of mixing ratio on the resulting data. Then, the derived conductivities were applied for 3D hypertonic saline-infused RFA simulation. The results matched our previous experimental measurements within 13%. The proposed model is customizable in constructing mixtures of multiple components, and can thus be expanded to include the effects of various anatomical microstructures and materials.

Pseudo-organ boundary conditions applied to a computational fluid dynamics model of the human aorta.

In three-dimensional numerical studies of the aorta, it is difficult to apply proper boundary conditions at the end of each major aortic branch because of interactions between blood and organs. Organs and body parts were assumed to be likened to cylindrically shaped porous media, so-called pseudo-organs, and treated in the computational domain as forms of hemodynamic resistance. Permeability functions were determined from two-dimensional axisymmetric computations of each aortic branch and these functions were then used in an unsteady three-dimensional simulation of the complete aorta. Substantially accurate cardiac output (5.91 L/min) and blood distributions to the major branches were predicted.