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Background/Aim: Glycosphingolipids are known to be involved in bone metabolism. However, their roles and regulatory mechanisms in osteoblast proliferation are largely unknown. In this study, we examined the effects of inhibitors of glucosylceramide synthase (GCS), which is responsible for the generation of all glycosphingolipids, on osteoblast proliferation. Materials and Methods: We analyzed the expression of glycosphingolipids and cell growth in MC3T3-E1 mouse osteoblast cells treated with the GCS inhibitors miglustat, D-PDMP and D-PPMP. We also conducted microarray analysis and RNA interference to identify genes involved in cell growth regulated by GCS. Results: Glycosphingolipids GD1a and Gb4 expressed in MC3T3-E1 cells, were suppressed by GCS inhibitors. Furthermore, the proliferation of MC3T3-E1 cells was suppressed by the inhibitors. Using microarray analysis, we predicted nine genes (Fndc1, Acta2, Igfbp5, Cox6a2, Cth, Mymk, Angptl6, Mab21l2, and Igsf10) suppressed by all three inhibitors. Furthermore, partial silencing of Angptl6 by RNA interference reduced MC3T3-E1 cell growth. Conclusion: These results show that GCS regulates proliferation through Angptl6 in osteoblasts.

A semi-Lagrangian-type advection scheme, the constrained profile interpolation (CIP) method, is adopted to obtain a numerical solution of a drift–diffusion equation of photo-generated charge carriers in negatively biased, high-resistivity semiconductor detector materials. Transient current waveforms of high-resistivity CdZnTe measured by a time-of-flight (TOF) technique under different bias voltages and various laser excitation intensities, are theoretically reproduced from the temporal evolution of the charge distribution and corresponding internal electric-field evolution, which are derived from the solution of the drift–diffusion equation, in combination with Poisson’s equation. The temporal evolution of the charge distribution and internal electric-field distribution obtained by the present theoretical technique agree very well with those obtained by a Monte Carlo (MC) simulation, an independent numerical technique. We demonstrate the validity of the present numerical technique by reproducing the excitation-intensity dependence of experimental TOF current waveforms measured in a CdZnTe crystal.

Gangliosides are widely expressed in almost all tissues and cells and are also considered to be essential in the development and maintenance of various organs and tissues. However, little is known about their roles in bone metabolism. In this study, we investigated the effects of genetic deletion of ganglioside D3 (GD3) synthase, which is responsible for the generation of all b-series gangliosides, on bone metabolism. Although b-series gangliosides were not expressed in osteoblasts, these gangliosides were expressed in pre-osteoclasts. However, the expression of these gangliosides was decreased after induction of osteoclastogenesis by receptor activator of nuclear factor kappa-B ligand (RANKL). Three-dimensional micro-computed tomography (3D-&mu, CT) analysis revealed that femoral cancellous bone mass in GD3 synthase-knockout (GD3S KO) mice was higher than that in wild type (WT) mice at the age of 40 weeks, although there were no differences in that between GD3S KO and WT mice at 15 weeks old. Whereas bone formation parameters (osteoblast numbers/bone surface and osteoblast surface/bone surface) in GD3S KO mice did not differ from WT mice, bone resorption parameters (osteoclast numbers/bone surface and osteoclast surface/bone surface) in GD3S KO mice became significantly lower than those in WT mice at 40 weeks of age. Collectively, this study demonstrates that deletion of GD3 synthase attenuates bone loss that emerges with aging.

In the spring of 2012, a year after the Fukushima Daiichi nuclear disaster, radiocesium-contaminated Japanese cedar pollen may have caused internal exposure to the general population by inhalation. To determine if pollen had been contaminated through uptake of radiocesium by Japanese cedars and was therefore contributing to inhalation doses, the authors measured radiocesium and Japanese cedar pollen adhered to masks worn by 68 human subjects residing in eastern Japan, including Fukushima prefecture, for 8 wk in the spring of 2012. The maximum cumulative Cs and Cs radioactivities on masks worn by an individual were 21 ± 0.36 Bq and 15 ± 0.22 Bq, respectively, and the estimated effective dose during the 8 wk was 0.494 μSv. The average estimated effective dose during the 8 wk was 0.149 μSv in Fukushima prefecture and 0.015 μSv in other prefectures, including Tokyo metropolitan. The correlation between radiocesium activity and the Japanese cedar pollen count was moderate. However, imaging-plate and light microscopy observations showed that the main source of radiocesium adhered to masks was fugitive dust.