Sweeteners interacting with the transmembrane domain of the human sweet-taste receptor induce sweet-taste synergisms in binary mixtures

Sweet enhancing effect of neohesperidin dihydrochalcone (NHDC) or cyclamate has been reported to be synergistic in human sensory tests. However, little is known about whether these synergisms are caused by the mechanism mediated by the human sweet-taste receptor. Here, we examined the sweetness intensity of sweet tastant mixtures by measuring the responses of cultured cells stably expressing the human sweet-taste receptor. The results showed that the cell response to sucrose was synergistically potentiated by the addition of NHDC or cyclamate. Moreover, a point mutation in the transmembrane domain of hT1R3 almost completely eliminated the enhancing effects of NHDC and cyclamate. These results suggest that ligand–receptor interactions in the transmembrane domain of hT1R3 are necessary for NHDC and cyclamate to elicit the synergistic potentiation of the receptor activation. Our results may provide the foundation of a molecular basis for receptor-based synergisms of sweet tastes in mixtures of diverse sweet substances.     

Effect of friction stir processing on microstructure of laser clad cobalt-based alloy

(The microstructural refinement of cobalt-based alloy (Stellite No. 6) by laser cladding and friction stir processing (FSP) was studied. A nanometer-sized microstructure consisting of fine carbide (particle size: 100–200 nm) and a grain (grain size: 150–250 nm) was successfully fabricated by the FSP on the laser clad cobalt-based alloy. The nanostructured cobalt-based alloy (Stellite No. 6) had an extremely high hardness of about 750 HV.     

Preparation and mesostructure control of highly ordered zirconia particles having crystalline walls

Mesostructured zirconia particles having monoclinic-type crystalline walls were prepared using a low-temperature crystallization technique. Crystalline zirconia particles with highly-ordered mesostructures were obtained through the sol–gel process of zirconium sulfate tetrahydrate at 333 K in the presence of molecular self-assemblies of cetyltrimethylammonium bromide (CTAB) or mixtures of CTAB and anionic molecules such as sodium dodecyl sulfate and sodium p-toluenesulfonate. Variations in the molar ratios of CTAB and the chemical species of anionic molecules led to the variations in the periods of highly-ordered zirconia having crystalline walls. Calcination of the mesostructured zirconia particles prepared using templates consisting solely of CTAB yielded crystalline mesoporous zirconia particles.     

Nickel‐Catalyzed Suzuki–Miyaura Coupling of a Tertiary Iodocyclopropane with Wide Boronic Acid Substrate Scope: Coupling Reaction Outcome Depends on Radical Species Stability

We describe a nickel‐catalyzed Suzuki–Miyaura arylation of a tertiary iodocyclopropane with arylboronic acids; this is an efficient and convergent strategy for providing various enantioenriched arylcyclopropanes with a quaternary stereogenic center. This is the first metal‐catalyzed coupling between a tertiary alkyl electrophile and a wide range of aromatics, including heteroaromatics. We found that the outcome of the Ni‐catalyzed coupling with halides as electrophiles was dependent on the stability of the radical species formed during the reaction. The use of tert‐butyl alcohol (t‐BuOH) as the reaction solvent was very effective, because of its stability under the radical‐generating reaction conditions.

     

Gene Expression over Time during Cell Transformation Due to Non-Genotoxic Carcinogen Treatment of Bhas 42 Cells

The Bhas 42 cell transformation assay (Bhas 42 CTA) is the first Organization for Economic Cooperation and Development (OECD)-certificated method used as a specific tool for the detection of the cell-transformation potential of tumor-promoting compounds, including non-genotoxic carcinogens (NGTxCs), as separate from genotoxic carcinogens. This assay offers the great advantage of enabling the phenotypic detection of oncotransformation. A key benefit of using the Bhas 42 CTA in the study of the cell-transformation mechanisms of tumor-promoting compounds, including non-genotoxic carcinogens, is that the cell-transformation potential of the chemical can be detected directly without treatment with a tumor-initiating compound since Bhas 42 cell line was established by transfecting the v-Ha-ras gene into a mouse fibroblast cloned cell line. Here, we analyzed the gene expression over time, using DNA microarrays, in Bhas 42 cells treated with the tumor-promoting compound 12-O-tetradecanoylphorbol-13-acetate (TPA), and NGTxC, with a total of three repeat experiments. This is the first paper to report on gene expression over time during the process of cell transformation with only a tumor-promoting compound. Pathways that were activated or inactivated during the process of cell transformation in the Bhas 42 cells treated with TPA were related not only directly to RAS but also to various pathways in the hallmarks of cancer.