Mast cells (MCs) mature locally, thus possessing tissue-dependent phenotypes for their critical roles in both protective immunity against pathogens and the development of allergy or inflammation. We previously reported that MCs highly express P2X7, a receptor for extracellular ATP, in the colon but not in the skin. The ATP-P2X7 pathway induces MC activation and consequently exacerbates the inflammation. Here, we identified the mechanisms by which P2X7 expression on MCs is reduced by fibroblasts in the skin, but not in the other tissues. The retinoic-acid-degrading enzyme Cyp26b1 is highly expressed in skin fibroblasts, and its inhibition resulted in the upregulation of P2X7 on MCs. We also noted the increased expression of P2X7 on skin MCs and consequent P2X7- and MC-dependent dermatitis (so-called retinoid dermatitis) in the presence of excessive amounts of retinoic acid. These results demonstrate a unique skin-barrier homeostatic network operating through Cyp26b1-mediated inhibition of ATP-dependent MC activation by fibroblasts.

Metal ions were determined by ESI-MS in the negative ion mode as monovalent negative ions of their aminopolycarboxylic acid (APC) complexes, e.g., [Al(cydta)](-), [Pb(Hcydta)](-), where excess amounts of the APC agents were added to sample solutions. Among several APCs studied, we chose trans-1,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid (CyDTA) as the best chelating agent because of higher stabilities and higher sensitivities of the complexes. The ionization efficiency of these metal complexes was strongly affected by the presence of matrix salts, e.g., NaCl, KNO(3), and etc. Thus, a size exclusion column (Sephadex G-10) was used for the online separation of the metal-APC complexes from other matrix salts. This method was successfully applied to the quantitative analyses for total amounts of Al, Ni, Cu, Zn, and Pb in the biological certified reference materials, olive leaves (BCR-062) and plankton (BCR-414). The detection limits of the present methods for these elements were several to several ten nanomolar levels. Moreover, this approach was extended to determine ultratraces of fluoride based on the formation of the ternary complex of aluminum, fluoride and nitrilotriacetic acid (NTA), i.e., [AlF(nta)](-). Its detection limit was 10 nM and was 2 orders of magnitude better than that of a fluoride ion selective electrode method. This method was applied to determine fluoride in tap water, river water, and green tea samples.

Cancer stem‐like cells (CSCs) induce drug resistance and recurrence of tumors when they experience DNA replication stress. However, the mechanisms underlying DNA replication stress in CSCs and its compensation remain unclear. Here, we demonstrate that upregulated c‐Myc expression induces stronger DNA replication stress in patient‐derived breast CSCs than in differentiated cancer cells. Our results suggest critical roles for mini‐chromosome maintenance protein 10 (MCM10), a firing (activating) factor of DNA replication origins, to compensate for DNA replication stress in CSCs. MCM10 expression is upregulated in CSCs and is maintained by c‐Myc. c‐Myc‐dependent collisions between RNA transcription and DNA replication machinery may occur in nuclei, thereby causing DNA replication stress. MCM10 may activate dormant replication origins close to these collisions to ensure the progression of replication. Moreover, patient‐derived breast CSCs were found to be dependent on MCM10 for their maintenance, even after enrichment for CSCs that were resistant to paclitaxel, the standard chemotherapeutic agent. Further, MCM10 depletion decreased the growth of cancer cells, but not of normal cells. Therefore, MCM10 may robustly compensate for DNA replication stress and facilitate genome duplication in cancer cells in the S‐phase, which is more pronounced in CSCs. Overall, we provide a preclinical rationale to target the c‐Myc‐MCM10 axis for preventing drug resistance and recurrence of tumors.

Structural and conformational determination of large and functional organic molecules is of great importance to understand their physical and chemical properties.Here we report on the length dependence of molecular shapes of long oligothiophene wires adsorbed on Au(111), which has been directly visualized by low-temperature scanning tunneling microscopy (STM). The controlled vacuum deposition of the oligothiophene wires from 10 to 120 nm in length has been accomplished by using an electrospray ionization technique. From the high-resolution STM images, we have observed that the oligothiophene molecules longer than around 60 nm tend to form folded (or looped) structures in order to keep compact shapes, which should reflect the molecular shapes in solution or in gas phase.