味覚修飾タンパク質ネオクリンがヒト甘味受容体を活性化する分子機構の研究

学位の種別: 課程博士審査委員会委員 : (主査)東京大学准教授 三坂 巧, 東京大学教授 佐藤 隆一郎, 東京大学特任教授 朝倉 富子, 東京大学准教授 永田 宏次, 東京大学准教授 寺田 透University of Tokyo(東京大学

New Supporting Evidence for the Overdensity of Galaxies around the Radio-Loud Quasar SDSS J0836+0054 at z =5.8

Recently, Zheng et al. (2005) found evidence for an overdensity of galaxies around a radio-loud quasar, SDSS J0836+0054, at z=5.8 (a five arcmin$^2$ region). We have examined our deep optical imaging data (B, V, r', i', z', and NB816) taken with the Suprime-Cam on the Subaru Telescope. The NB816 narrow-band filter (lambda_c = 815 nm and $\Delta\lambda = 12$ nm) is suitable for searching for Ly$\alpha$ emitters at $z\approx 5.7$. We have found a new strong Ly$\alpha$ emitter at $z \approx 5.7$ close to object B identified by Zheng et al. Further, the non detection of the nine objects selected by Zheng et al. (2005) in our B, V, and r' images provides supporting evidence that they are high-z objects.Comment: 5 pages, 1 figure, accepted for PAS

Strong Emission-Line Galaxies at Low Redshift in the Field around the Quasar SDSSp J104433.04-012502.2

We discuss observational properties of strong emission-line galaxies at low redshift found by our deep imaging survey for high-redshift Ly alpha emitters. In our surveys, we used the narrowband filter, NB816 (lambda_center=8150A with FWHM = 120A), and the intermediate-band filter, IA827 (lambda_center = 8270A with FWHM = 340A). In this survey, 62 NB816-excess (> 0.9 mag) and 21 IA827-excess (> 0.8 mag) objects were found. Among them, we found 20 NB816-excess and 4 IA827-excess Ly alpha emitter candidates. Therefore, it turns out that 42 NB816-excess and 17 IA827-excess objects are strong emission-line objects at lower redshift. Since 4 objects in the two low-z samples are common, the total number of strong low-z emitters is 55. Applying our photometric redshift technique, we identify 7 H alpha emitters at z~0.24, 20 H beta-[OIII] ones at z~0.65, and 11 [OII] ones at z~1.19. However, we cannot determine reliable photometric redshifts of the remaining 17 emitters. The distributions of their rest frame equivalent widths are consistently understood with recent studies of galaxy evolution from z~1 to z~0.Comment: 28 pages, 8 figures, PASJ, Vol. 58, No. 1, in pres

Identification and Modulation of the Key Amino Acid Residue Responsible for the pH Sensitivity of Neoculin, a Taste-Modifying Protein

Neoculin occurring in the tropical fruit of Curculigo latifolia is currently the only protein that possesses both a sweet taste and a taste-modifying activity of converting sourness into sweetness. Structurally, this protein is a heterodimer consisting of a neoculin acidic subunit (NAS) and a neoculin basic subunit (NBS). Recently, we found that a neoculin variant in which all five histidine residues are replaced with alanine elicits intense sweetness at both neutral and acidic pH but has no taste-modifying activity. To identify the critical histidine residue(s) responsible for this activity, we produced a series of His-to-Ala neoculin variants and evaluated their sweetness levels using cell-based calcium imaging and a human sensory test. Our results suggest that NBS His11 functions as a primary pH sensor for neoculin to elicit taste modification. Neoculin variants with substitutions other than His-to-Ala were further analyzed to clarify the role of the NBS position 11 in the taste-modifying activity. We found that the aromatic character of the amino acid side chain is necessary to elicit the pH-dependent sweetness. Interestingly, since the His-to-Tyr variant is a novel taste-modifying protein with alternative pH sensitivity, the position 11 in NBS can be critical to modulate the pH-dependent activity of neoculin. These findings are important for understanding the pH-sensitive functional changes in proteinaceous ligands in general and the interaction of taste receptor–taste substance in particular

Phosphodiesterase Inhibitors Suppress Lactobacillus casei Cell-Wall-Induced NF-κB and MAPK Activations and Cell Proliferation through Protein Kinase A—or Exchange Protein Activated by cAMP-Dependent Signal Pathway

Specific strains of Lactobacillus have been found to be beneficial in treating some types of diarrhea and vaginosis. However, a high mortality rate results from underlying immunosuppressive conditions in patients with Lactobacillus casei bacteremia. Cyclic AMP (cAMP) is a small second messenger molecule that mediates signal transduction. The onset and progression of inflammatory responses are sensitive to changes in steady-state cAMP levels. L. casei cell wall extract (LCWE) develops arteritis in mice through Toll-like receptor-2 signaling. The purpose of this study was to investigate whether intracellular cAMP affects LCWE-induced pathological signaling. LCWE was shown to induce phosphorylation of the nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways and cell proliferation in mice fibroblast cells. Theophylline and phosphodiesterase inhibitor increased intracellular cAMP and inhibited LCWE-induced cell proliferation as well as phosphorylation of NF-κB and MAPK. Protein kinase A inhibitor H89 prevented cAMP-induced MAPK inhibition, but not cAMP-induced NF-κB inhibition. An exchange protein activated by cAMP (Epac) agonist inhibited NF-κB activation but not MAPK activation. These results indicate that an increase in intracellular cAMP prevents LCWE induction of pathological signaling pathways dependent on PKA and Epac signaling

A survey of NB921 dropouts in the Subaru Deep Field

In order to search for high-redshift galaxies beyond $z = 6.6$ in the Subaru Deep Field, we have investigated NB921-dropout galaxies where NB921 is the narrowband filter centered at 919.6 nm with FWHM of 13.2 nm for the Suprime-Cam on the Subaru Telescope. There are no secure NB921-dropout candidates brighter than $z^\prime = 25.5$. Based on this result, we discuss the UV luminosity function of star-forming galaxies at $z > 6.6$.Comment: 10 pages, 5 figures, PASJ, Vol.57, No.5, in pres

Survey of Period Variations of Superhumps in SU UMa-Type Dwarf Novae

We systematically surveyed period variations of superhumps in SU UMa-type dwarf novae based on newly obtained data and past publications. In many systems, the evolution of superhump period are found to be composed of three distinct stages: early evolutionary stage with a longer superhump period, middle stage with systematically varying periods, final stage with a shorter, stable superhump period. During the middle stage, many systems with superhump periods less than 0.08 d show positive period derivatives. Contrary to the earlier claim, we found no clear evidence for variation of period derivatives between superoutburst of the same object. We present an interpretation that the lengthening of the superhump period is a result of outward propagation of the eccentricity wave and is limited by the radius near the tidal truncation. We interpret that late stage superhumps are rejuvenized excitation of 3:1 resonance when the superhumps in the outer disk is effectively quenched. Many of WZ Sge-type dwarf novae showed long-enduring superhumps during the post-superoutburst stage having periods longer than those during the main superoutburst. The period derivatives in WZ Sge-type dwarf novae are found to be strongly correlated with the fractional superhump excess, or consequently, mass ratio. WZ Sge-type dwarf novae with a long-lasting rebrightening or with multiple rebrightenings tend to have smaller period derivatives and are excellent candidate for the systems around or after the period minimum of evolution of cataclysmic variables (abridged).Comment: 239 pages, 225 figures, PASJ accepte

Spatiotemporal dynamics of single cell stiffness in the early developing ascidian chordate embryo

During the developmental processes of embryos, cells undergo massive deformation and division that are regulated by mechanical cues. However, little is known about how embryonic cells change their mechanical properties during different cleavage stages. Here, using atomic force microscopy, we investigated the stiffness of cells in ascidian embryos from the fertilised egg to the stage before gastrulation. In both animal and vegetal hemispheres, we observed a Rho kinase (ROCK)-independent cell stiffening that the cell stiffness exhibited a remarkable increase at the timing of cell division where cortical actin filaments were organized. Furthermore, in the vegetal hemisphere, we observed another mechanical behaviour, i.e., a ROCK-associated cell stiffening, which was retained even after cell division or occurred without division and propagated sequentially toward adjacent cells, displaying a characteristic cell-to-cell mechanical variation. The results indicate that the mechanical properties of embryonic cells are regulated at the single cell level in different germ layers. Fujii et al. investigate the stiffness of cells in ascidian embryos from the fertilised egg to the stage before gastrulation. They find two types of cell stiffening, occurring during cell division and in the interphase, the latter of which is associated with the Rho kinase pathway. They conclude that the mechanical properties of early embryonic cells are regulated specifically at the single cell level