Bone morphogenetic protein 4 (BMP4) has potential as an anticancer agent. Recent studies have suggested that BMP4 inhibits the survival of cancer stem cells (CSCs) of neural and colon cancers. Here, ...we showed that BMP4 paracrinically inhibited tumor angiogenesis via the induction of Thrombospondin-1 (TSP1), and consequently suppressed tumor growth in vivo. Although HeLa (human cervical cancer), HCI-H460-LNM35 (highly metastatic human lung cancer) and B16 (murine melanoma) cells did not respond to the BMP4 treatment in vitro, the growth of xeno- and allografts of these cells was suppressed via reductions in tumor angiogenesis after intraperitoneal treatment with BMP4. When we assessed the mRNA expression of major angiogenesis-related factors in grafted tumors, we found that the expression of TSP1 was significantly upregulated by BMP4 administration. We then confirmed that BMP4 was less effective in suppressing the tumor growth of TSP1-knockdown cancer cells. Furthermore, we found that BMP4 reduced vascular endothelial growth factor (VEGF) expression in vivo in a TSP1-dependent manner, which indicates that BMP4 interfered with the stabilization of tumor angiogenesis. In conclusion, the BMP4/TSP1 loop paracrinically suppressed tumor angiogenesis in the tumor microenvironment, which subsequently reduced the growth of tumors. BMP4 may become an antitumor agent and open a new field of antiangiogenic therapy.
Through numerical simulations, it is predicted that the gravitational waves (GWs) reflect the characteristics of the core-collapse supernova (CCSN) explosion mechanism. There are multiple GW ...excitation processes that occur inside a star before its explosion, and it is suggested that the GWs originating from the CCSN have a mode for each excitation process in terms of time-frequency representation. Therefore, we propose an application of the Hilbert-Huang transform (HHT), which is a high-resolution time-frequency analysis method, to analyze these GW modes for theoretically probing and increasing our understanding of the explosion mechanism. The HHT defines frequency as a function of time, and is not bound by the trade-off between time and frequency resolutions. In this study, we analyze a gravitational waveform obtained from a three-dimensional general-relativistic CCSN model that showed a vigorous activity of the standing-accretion-shock-instability (SASI). We succeed in extracting the SASI induced GWs with high resolution on a time-frequency representation using the HHT and we examine their instantaneous frequencies.
Summary
The regenerating gene (Reg) was isolated originally as a gene specifically over‐expressed in regenerating pancreatic islets and constitute a growth factor family. Reg gene product (Reg) is ...important in the pathophysiology of various human inflammatory diseases. Recently, the possible involvement of human REG in the regeneration of salivary ductal epithelial cells of patients with primary Sjögren's syndrome (SS) was reported. However, the expression of the REG family genes in minor salivary glands (MSG) and the occurrence of anti‐REG Iα autoantibodies in SS patients were obscured. In this study, we examined the expression of REG family genes in the MSG of SS and screened anti‐REG Iα autoantibodies in SS. The mRNA levels of REG family genes in MSG were quantified using real‐time reverse transcription–polymerase chain reaction (RT–PCR) and REG Iα expression in the MSG was analysed by immunohistochemistry. The mRNA level of REG Iα in the MSG of SS patients was significantly higher than that of control. REG Iα protein was expressed highly in SS ductal epithelial cells. Anti‐REG Iα autoantibodies in the sera were found in 11% of SS. All the MSG in the anti‐REG Iα autoantibody‐positive group showed REG Iα expression, whereas only 40% showed REG Iα expression in the anti‐REG Iα autoantibody‐negative group. The anti‐REG Iα autoantibody‐positive group showed significantly lower saliva secretion and a higher ratio of grade 4 (by Rubin–Holt) in sialography. These data suggest strongly that autoimmunity to REG Iα might play a role in the degeneration of MSG ductal epithelial cells in primary SS.
In monsoon Asia, optical satellite remote sensing for rice paddy phenology suffers from atmospheric contaminations mainly due to frequent cloud cover. We evaluated the quality of satellite remote ...sensing of paddy phenology: (1) through continuous in situ observations of a paddy field in Japan for 1.5 years, we investigated phenological signals in the reflectance spectrum of the paddy field; (2) we tested daily satellite data taken by Terra/Aqua MODIS (MOD09 and L1B products) with regard to the agreement with the in situ data and the influence of cloud contamination. As a result, the in situ spectral characteristics evidently indicated some phenological changes in the rice paddy field, such as irrigation start, padding, heading, harvest and ploughing. The Enhanced Vegetation Index (EVI) was the best vegetation index in terms of agreement with the in situ data. More than 65% of MODIS observations were contaminated with clouds in this region. However, the combined use of Terra and Aqua decreased the rate of cloud contamination of the daily data to 43%. In conclusion, the most robust dataset for monitoring rice paddy phenology in monsoon Asia would be daily EVI derived from a combination of Terra/MODIS and Aqua/MODIS.
The reflectance-based vicarious calibration approach has been applied to the Advanced spaceborne Thermal emission and reflection radiometer (ASTER) that is on the Terra platform. The results from ...three separate groups operating at the same sites at the same time are presented. The three groups show good agreement between each other, with differences between the groups being smaller than 4% in all bands ranging from 0.6 to 2.2 mum and with larger differences being seen at shorter wavelengths and beyond 2.2 mum. comparisons between the groups and to the ASTER sensor are best at 1.66 mum (band 4), with differences between each group being less than 0.5% and all of the groups agreeing with ASTER to better than 5%. Differences in the visible and near infrared (VNIR) are larger, particularly prior to August 2002 when an update to the calibration processing was performed. These differences exceed 10% in some bands. In addition, the vicarious results appear to show a different trend than the onboard calibration for the VNIR indicating a possible problem with the onboard calibrator for bands 1-3.
This work investigated the effect of oxide in Ni-zirconia cermets on the carbon deposition behavior in internal reforming SOFCs. Within 800-1000 deg C, carbon deposition was found to decrease with ...increasing temperature on Ni/ScSZ cermet anodes at a low oxygen/carbon ratio (O/C=0.03) during anodic oxidation of methane. On the contrary, an opposite trend was observed on Ni/YSZ under the same conditions, consisting with the temperature dependence of carbon deposition predicted by a thermodynamic equilibrium calculation. Results of temperature-programmed-reduction (TPR) of NiO mixed with YSZ or ScSZ indicated that interaction of Ni with ScSZ is stronger than that with YSZ. The stronger interaction was corroborated by observed tendency of inhibiting Ni agglomeration by both BET specific surface area analysis and SEM observation. It was also found that the dependence of CO2 production rate monitored by GC on current density showed a similar dependence trend of the equilibrium CO2 content on O/C ratio. A model in which H2Oad enrichment effects on Ni surface by anodic current depend on the interaction between Ni and the oxide in Ni cermet was proposed to explain the different carbon deposition behaviors between Ni/YSZ and Ni/ScSZ cermets.
Osteoblasts play essential roles in bone formation and regeneration, while they have low proliferation potential. Recently we established a procedure to directly convert human fibroblasts into ...osteoblasts (dOBs). Transduction of Runx2 (R), Osterix (X), Oct3/4 (O) and L-myc (L) genes followed by culturing under osteogenic conditions induced normal human fibroblasts to express osteoblast-specific genes and produce calcified bone matrix both in vitro and in vivo Intriguingly, a combination of only two factors, Oct3/4 and L-myc, significantly induced osteoblast-like phenotype in fibroblasts, but the mechanisms underlying the direct conversion remains to be unveiled.
We examined which Oct family genes and Myc family genes are capable of inducing osteoblast-like phenotypic conversion.
As result Oct3/4, Oct6 and Oct9, among other Oct family members, had the capability, while N-myc was the most effective Myc family gene. The Oct9 plus N-myc was the best combination to induce direct conversion of human fibroblasts into osteoblast-like cells.
The present findings may greatly contribute to the elucidation of the roles of the Oct and Myc proteins in osteoblast direct reprogramming. The results may also lead to establishment of novel regenerative therapy for various bone resorption diseases.
•Introducing L-myc in a combination with either Oct3/4, Oct6 or Oct9 enables the conversion of fibroblasts to osteoblasts.•A combination of L-myc with Oct3/4 or Oct9 can induce the cells to a phenotype closer to normal osteoblasts.•N-myc was considered the most appropriate Myc family gene for induction of osteoblast-like phenotype in fibroblasts.•The combination of Oct9 plus N-myc has the strongest capability of inducing osteoblast-like phenotype.
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