Bisphosphonate inhibits the expression of cyclin A2 at the transcriptional level in normal human oral keratinocytes.

Nitrogen-containing bisphosphonates (N-BPs) are the most widely used anti-resorptive agents in the treatment of bone-related diseases. N-BPs inhibit bone resorption by specifically targeting osteoclasts, bone-resorbing cells. However, soft tissue toxicity, such as oral or gastrointestinal (GI) ulcerations has frequently been reported in N-BP users, suggesting that N-BPs may also directly target cells other than osteoclasts. Previously, we reported that BPs inhibit proliferation without inducing the apoptosis of normal human oral keratinocytes (NHOKs). However, the molecular mechanisms through which N-BPs inhibit the proliferation of NHOKs are not yet fully understood. In this study, we performed gene expression profiling in N-BP-treated NHOKs and identified cyclin A2 as one of the most commonly downregulated genes. When the NHOKs were treated with N-BPs, we found that the level of cyclin A2 was suppressed in a dose- and time-dependent manner. In addition, the protein level of cyclin A2 was also significantly lower in oral epithelial cells in N-BP-treated oral mucosal tissue constructs. Cyclin A2 promoter reporter assay revealed that N-BPs inhibited the luciferase activity, indicating that the inhibition of cyclin A2 expression occurs at the transcriptional level. Furthermore, N-BPs did not alter the expression of cyclin A2 in normal human oral fibroblasts (NHOFs), suggesting that the effect of N-BPs on cyclin A2 expression may be cell-type specific. Thus, the findings of our study demonstrate that the inhibition of NHOK proliferation by N-BPs is mediated, at least in part, by the suppression of cyclin A2 expression at the transcriptional level, which may explain the underlying mechanisms of soft tissue toxicity by N-BPs

Role of the dimerized gap due to anion ordering in spin-density wave phase of (TMTSF)2_2ClO4_4 at high magnetic fields

Magnetoresistance measurements have been carried out along the highly conducting a axis in the FISDW phase of hydrogened and deuterated (TMTSF)$_2$ClO$_4$ for various cooling rates through the anion ordering temperature. With increasing the cooling rate, a) the high field phase boundary $\beta_{\rm {HI}}$, observed at 27 T in hydrogened samples for slowly cooled, is shifted towards a lower field, b) the last semimetallic SDW phase below $\beta_{\rm {HI}}$ is suppressed, and c) the FISDW insulating phase above $\beta_{\rm {HI}}$ is enhanced in both salts. The cooling rate dependence of the FISDW transition and of $\beta_{\rm {HI}}$ in both salts can be explained by taking into account the peculiar SDW nesting vector stabilized by the dimerized gap due to anion ordering.Comment: 6pages,6figures(EPS), accepted for publication in PR

Electronic structure of YbB6_{6}: Is it a Topological Insulator or not?

To resolve the controversial issue of the topological nature of the electronic structure of YbB$_{6}$, we have made a combined study using density functional theory (DFT) and angle resolved photoemission spectroscopy (ARPES). Accurate determination of the low energy band topology in DFT requires the use of modified Becke-Johnson exchange potential incorporating the spin-orbit coupling and the on-site Coulomb interaction $U$ of Yb $4f$ electrons as large as 7 eV. We have double-checked the DFT result with the more precise GW band calculation. ARPES is done with the non-polar (110) surface termination to avoid band bending and quantum well confinement that have confused ARPES spectra taken on the polar (001) surface termination. Thereby we show definitively that YbB$_{6}$ has a topologically trivial B 2$p$-Yb 5$d$ semiconductor band gap, and hence is a non-Kondo non-topological insulator (TI). In agreement with theory, ARPES shows pure divalency for Yb and a $p$-$d$ band gap of 0.3 eV, which clearly rules out both of the previous scenarios of $f$-$d$ band inversion Kondo TI and $p$-$d$ band inversion non-Kondo TI. We have also examined the pressure-dependent electronic structure of YbB$_{6}$, and found that the high pressure phase is not a Kondo TI but a \emph{p}-\emph{d} overlap semimetal.Comment: The main text is 6 pages with 4 figures, and the supplementary information contains 6 figures. 11 pages, 10 figures in total To be appeared in Phys. Rev. Lett. (Online publication is around March 16 if no delays.

Quantum Nucleation in a Ferromagnetic Film Placed in a Magnetic Field at an Arbitrary Angle

We study the quantum nucleation in a thin ferromagnetic film placed in a magnetic field at an arbitrary angle. The dependence of the quantum nucleation and the temperature of the crossover from thermal to quantum regime on the direction and the strength of the applied field are presented. It is found that the maximal value of the rate and that of the crossover temperature are obtained at a some angle with the magnetic field, not in the direction of the applied field opposite to the initial easy axis.Comment: 15 pages, RevTex, 3 PostScript figures. To appear in Phys. Rev.

Action of Retinoids on Embryonic and Early Postnatal Testis Development

The current study investigates the hypothesis that retinoids have a role in embryonic testis development. The action of retinoids on testis development and the expression of retinoic acid receptors (RARα, RARβ, RARγ) were examined. In embryonic day 13 (E13; plug date 5 E0) testis organ cultures an RAR-selective agonist and alltrans retinoic acid completely inhibited seminiferous cord formation. In contrast, an RARα-selective antagonist had no effect. RT-PCR demonstrated that RARα messenger RNA (mRNA) was expressed at all developmental time points evaluated, which included embryonic day 14 (E14) through postnatal day 30 (P30). Expression of RARβ mRNA was present at E15 through P2, whereas RARγ mRNA was expressed at E18 through P2. Cellular localization of receptors by immunohistochemistry indicated that RARα was localized to the interstitium at E18 and to the seminiferous cords by P0. RARβ and RARγ were detected in both interstitium and cords at E16 and by E18 were mainly expressed in the cords. At P0 RARβ and RARγ were localized to the germ cell populations. To examine retinoid actions, the growth of P0 testis cultures were investigated. Interestingly, retinol and retinoic acid did not inhibit growth of P0 testis cultures but did inhibit the action of growth stimulators. Retinoic acid inhibited FSH, EGF, and 10% calf serum stimulated growth in P0 testis cultures. The hypothesis tested was that the inhibitory effects of retinoids on P0 testis growth may be mediated through the growth inhibitor, transforming growth factor-b (TGFβ). The action of retinoids on TGFβ mRNA expression was examined in P0 testis cultures. Retinoic acid stimulated TGFβ3 mRNA expression within 24 h and increased expression of TGFβ1 and TGFβ2 after 72 h. Retinol increased expression of TGFβ1 and TGFβ2 but not TGFβ3 after 72 h of treatment. These observations indicate that retinoic acid can influence seminiferous cord formation and testis growth. The inhibitory actions of retinoids may in part be mediated through increased expression of TGFβ isoforms

Irreversible proliferation of magnetic moments at cleaved surfaces of the topological Kondo insulator SmB6

The compound SmB$_6$ is the best established realization of a topological Kondo insulator, in which a topological insulator state is obtained through Kondo coherence. Recent studies have found evidence that the surface of SmB$_6$ hosts ferromagnetic domains, creating an intrinsic platform for unidirectional ballistic transport at the domain boundaries. Here, surface-sensitive X-ray absorption (XAS) and bulk-sensitive resonant inelastic X-ray scattering (RIXS) spectra are measured at the Sm N$_{4,5}$-edge, and used to evaluate electronic symmetries, excitations and temperature dependence near the surface of cleaved samples. The XAS data show that the density of large-moment atomic multiplet states on a cleaved surface grows irreversibly over time, to a degree that likely exceeds a related change that has recently been observed in the surface 4f orbital occupation