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Biomedical subjects

S Nunomura

Publications and source records attributed to S Nunomura.

At least 19 recordsLinked to original sources

Self-diffusion in a liquid complex plasma.

Self-diffusion has been experimentally studied in a two-dimensional underdamped liquid complex (dusty) plasma. It was found that the self-diffusion coefficient D increases linearly with the temperature T: D/omega(E)a2 = (0.019 +/- 0.007)(T/T(m) - 1), where T(m), omega(E), and a are the melting temperature, the Einstein frequency, and the mean particle separation, respectively. No superdiffusion was observed, whereas a subdiffusion occurred at temperatures close to melting.

Journal Article↗

Heat transfer in a two-dimensional crystalline complex (dusty) plasma.

Heating and heat transfer were studied in a two-dimensional crystalline complex plasma at the kinetic level. The lattice was formed of microspheres levitated in a plasma sheath. One half of the crystal was heated anisotropically to obtain higher kinetic temperatures in one direction and heat conduction was observed in real time. It was found that the longitudinal phonons conduct heat better than the transverse. The thermometric conductivity coefficient was measured to be 53 mm2/s for longitudinal heating and 30 mm2/s for transverse heating. Heat decay lengths and energy exchange times between the temperature components were determined.

Journal Article↗

Wave spectra in solid and liquid complex (dusty) plasmas.

Spectra of longitudinal and transverse waves were obtained experimentally in liquid and solid two-dimensional complex (dusty) plasmas at different kinetic temperatures. As the temperature increased and the phase state of the plasma changed from solid to liquid, the phonon spectra of both longitudinal and transverse modes broadened (especially at high wave numbers), indicating increased damping. The transverse mode disappeared and a thermal (compressional) mode appeared.

Journal Article↗

Common and distinct signalling cascades in the production of tumour necrosis factor-alpha and interleukin-13 induced by lipopolysaccharide in RBL-2H3 cells.

BACKGROUND: Activation of mast cells by lipopolysaccharide (LPS) results in the production of TNF-alpha and IL-13. TNF-alpha and IL-13 are key mediators in the development of neutrophilic and allergic inflammation, respectively. LPS-induced TNF-alpha and IL-13 production in mast cells has been reported to be mediated by Toll-like receptor 4 (TLR4) signalling, but differences in signal transduction mechanisms leading to the production of these cytokines are not clearly defined. OBJECTIVE: We investigated the molecular mechanisms responsible for LPS-induced TNF-alpha and IL-13 production in mast cells. METHODS: TNF-alpha and IL-13 production by LPS was assessed by transfecting RBL-2H3 cells with dominant-negative (DN) expression vectors. RESULTS: Transfection of RBL-2H3 cells with plasmids encoding DN mutants of myeloid differentiation protein (MyD88) and TNFR-associated factor (TRAF6) inhibited both LPS-induced TNF-alpha and IL-13 production. IkappaBalpha-DN inhibited LPS-induced production of TNF-alpha, but not IL-13. We also found that inhibition of p38 kinase suppressed both TNF-alpha and IL-13 induction by LPS, and inhibition of JNK reduced IL-13 production, but not TNF-alpha. Furthermore, we found that protein kinase R (PKR) was activated by LPS in these cells. Treatment with 2-aminopurine, a PKR inhibitor, attenuated LPS-induced nuclear factor-kappaB activation and TNF-alpha production, whereas inhibition of PKR had little effect on IL-13 production. CONCLUSION: These findings indicate that the production of TNF-alpha and IL-13 by LPS required TLR4/MyD88/TRAF6 signalling as a common pathway of mast cell-mediated inflammation. We furthermore found that TNF-alpha and IL-13 production were differentially regulated by signalling cascades through PKR and mitogen-activated protein kinases downstream of TRAF6 in mast cells.

Adaptor Proteins, Signal Transducing↗

Polarization of wave modes in a two-dimensional hexagonal lattice using a complex (dusty) plasma.

Wave spectra corresponding to the random particle motion in a monolayer Yukawa crystal were studied for various directions of propagation. It was found that there are two wave modes with a polarization alternating between the longitudinal and transverse. In the long-wavelength regime, the modes became purely longitudinal and transverse as was known before. In the short-wavelength regime the spectra strongly depended on the wavelength and the direction of propagation. The results obtained from the experiment, theory, and simulation agreed well with each other.

Journal Article↗

Nonlinear longitudinal waves in a two-dimensional screened Coulomb crystal.

Nonlinear interactions of longitudinal waves were observed in a two-dimensional plasma crystal, i.e., a lattice composed of highly charged microspheres immersed in a plasma. The waves were launched by radiation pressure of a laser, and wave spectra in omega-k space were analyzed at various amplitudes of waves. At a sufficiently large amplitude of wave, the second and third wave harmonics satisfying a dispersion relation were observed. As the second harmonic propagates from the excitation region, it was amplified for a small distance, and then damped. The experimental results were compared to a nonlinear wave theory and to a molecular dynamic simulation.

Journal Article↗

Phonon spectrum in a plasma crystal.

The Fourier spectra of longitudinal and transverse waves corresponding to random particle motion were measured in a two-dimensional plasma crystal. The crystal was composed of negatively charged microspheres immersed in a plasma at a low gas pressure. The phonons were found to obey a dispersion relation that assumes a Yukawa interparticle potential. The crystal was in a nonthermal equilibrium, nevertheless phonon energies were almost equally distributed with respect to wave number over the entire first Brillouin zone.

Journal Article↗

Dispersion relations of longitudinal and transverse waves in two-dimensional screened Coulomb crystals.

Dispersion relations of longitudinal and transverse waves in two-dimensional (2D) screened-Coulomb crystals were investigated. The waves were excited in 2D crystals made from complex plasmas, i.e., dusty plasmas, by applying radiation pressure of laser light. The dependencies of the dispersion relation on the shielding parameter, the damping rate, and the wave propagation direction were experimentally measured. The measured dispersion relations agree reasonably with a recently developed theory, and the comparison yields the shielding parameter and the charge on particles.

Journal Article↗

Nonlinear compressional pulses in a 2D crystallized dusty plasma.

Compressional pulses were launched in a two-dimensional Yukawa lattice, a hexagonal monolayer of polymer microspheres suspended in a plasma. The pulsed wave was excited by a laser beam, and nonlinear effects were observed for Mach numbers M>0.07 and for variation of particle number density delta(n)/n>0.1, but no steepening of the pulse was detected. The pulse propagation speed was found to be comparable to the sound speed of compressional waves launched with sinusoidal excitation.

Journal Article↗

Surface molecules essential for positive selection are retained but interfered in thymic epithelial cells after monolayer culture.

It has been reported that the three-dimensional structure of thymic epithelial cells (TECs) is responsible for thymic positive selection but that this ability disappears when TECs are cultured in monolayer. These results have supported the hypothesis that certain TEC-specific molecules are extinguished during monolayer culture. In this study, using MHC class II-restricted T-cell receptor transgenic mice, we demonstrated that preselected CD4(+)8(+) (DP) thymocytes were inhibited from developing into CD4(+)8(-) (CD4SP) cells in reaggregate thymus organ culture with monolayer-cultured TECs, but this inhibition was removed when TECs were cultured in monolayer with protein synthesis inhibitor or when the cultured TECs were treated with fixative. These results seem to be inconsistent with the previous hypothesis and indicate that monolayer culture allows TECs to retain the surface molecules necessary for positive selection but interferes with their function, which must be sustained for three dimensional structure.

Animals↗

Molecular basis for functional maturation of thymocytes: increase in c-fos translation with positive selection.

In the process of positive selection, immature CD4+8+ double positive (DP) thymocytes expressing TCR reactive to self-MHC by appropriate avidity develop into mature thymocytes. Positive selection involves not only down-regulation of either CD4 or CD8 but also acquisition of immunocompetent potential such as cell proliferation and cytokine production. To understand the molecular basis for such functional maturation during the positive selection process, we examined whether nonselected DP, selected DP, and CD4+8- single positive thymocytes possess the activation potential for signaling pathways from mitogen-activated protein kinases (extracellular signal-regulated kinase and c-Jun N-terminal kinase) to AP-1. In response to stimulation, a marked induction of c-Fos protein expression as well as cell proliferation is detected only in CD4+8- single positive cells but not in selected and nonselected DP cells, though mitogen-activated protein kinase activities and c-fos transcripts are equally induced. In the presence of proteasome inhibitors, c-Fos protein became detectable in selected DP cells but still not in nonselected DP cells, suggesting that DP cells receiving positive selection signals acquire the capacity to translate the c-fos gene, but it may not be sufficiently high to overcome the degradation of c-Fos protein. These data indicate that the translating ability of the c-fos gene is up-regulated in the thymic positive selection process, from nonselected DP to CD4+8- single positive cells through positively selected DP cells. The distinguished responsiveness to stimulation in thymocytes with and without positive selection may be a result in part of the distinct regulation of the c-fos gene at the translational level.

Animals↗

Transverse waves in a two-dimensional screened-coulomb crystal (Dusty plasma)

Transverse shear waves were observed experimentally in a two-dimensional screened Coulomb crystal. They were excited by applying a chopped laser beam to a 2D dusty plasma, i.e., a monolayer of charged microspheres levitated in a plasma. Measurements of the dispersion relation reveal an acoustic, i.e., nondispersive, character over the entire range of wave numbers measured, 0.2<k(r)a/pi<0.7, where a is the interparticle spacing. Comparison to theory provides a measurement of the particles' charge.

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Effect of synthetic sialyl 2-->1 sphingosine and other glycosylsphingosines on the structure and function of the "glycosphingolipid signaling domain (GSD)" in mouse melanoma B16 cells.

Mouse melanoma B16 cells are characterized by a high concentration of GM3 ganglioside, which has been identified as a melanoma-associated antigen and is present as a clustered microdomain organized with major signal transducers, c-Src, small G-protein (Rho A), and focal adhesion kinase (FAK), to form a "glycosphingolipid signaling domain" or "glycosignaling domain" (GSD) separable from cholesterol- and caveolin-enriched microdomain, "caveolae." Cholesterol-binding reagents, filipin and nystatin, disrupt the structure and function of caveolae, but have no effect on GSD function [Iwabuchi, K., et al. (1998) J. Biol. Chem. 273, 33766-33773]. In this study, we searched for compounds which disrupt the structure and function of GSD in B16 cells. Such compounds should have structural features analogous to those of GM3, destroy or reduce clustering of GM3 in GSD, and inhibit GM3-dependent adhesion and signaling. The simplest compound so far found with these properties is sialyl alpha2-->1 sphingosine (Sph). We describe the synthesis of this compound and its analogues, and their effects on GM3 expression pattern and GSD function, in comparison with effects of lyso-GM3 and other lyso compounds, in B16 cells. Incubation of B16 cells with 0.5-10 microM sialyl alpha2-->1 Sph or 1-5 microM lyso-GM3 reduced GM3 clustering and GM3-dependent adhesion, and inhibited adhesion-dependent cellular FAK activity. The c-Src activation response of GSD isolated from B16 cells was inhibited strongly by sialyl alpha2-->1 Sph. Substitution of the Sph amino group with a chloroacetyl or N,N-dimethyl group strongly reduced the inhibitory effect of sialyl alpha2-->1 Sph on GM3-dependent adhesion, FAK, and c-Src response. Other lyso compounds such as lyso-phosphatidylcholine, galactosyl-Sph (psychosine), and lactosyl-Sph at 0.5-10 microM did not show the same effect as sialyl alpha2-->1 Sph. Thus, adhesion coupled with signal transduction, initiated by clusters of GM3 in GSD, is blocked by sialyl alpha2-->1 Sph or lyso-GM3. Analogues with N-substitution of Sph in sialyl alpha2-->1 Sph, other lyso-phospholipids, and galactosyl- or lactosyl-Sph did not block such adhesion, coupled with activation of c-Src and FAK.

Animals↗

Laser-excited mach cones in a dusty plasma crystal

Experimental studies of the formation and structure of Mach cones in a plasma crystal are presented. Plasma crystals are ordered structures of charged microspheres trapped in the sheath of an rf discharge plasma. Using a monolayer crystal with a hexagonal lattice, Mach cones were excited by the radiation pressure of a focused laser beam. The beam was swept at a supersonic speed through the crystal, in a controlled and repeatable manner. A multiple Mach cone structure was observed, with at least three distinct Mach cones. The Mach angle relation was verified over a wide range of Mach numbers, for both the first and second cones. The sound speed, measured from the first Mach angle, was found to increase with the particle number density. Two methods of determining the particle charge and screening distance are developed, making use of the sound speed and an assumption of a Yukawa interparticle potential. Molecular-dynamics simulations of the experiment were carried out, using a monolayer of particles interacting through a Yukawa potential, and these show close agreement with the experiment.

Journal Article↗

CD45 can act as a negative regulator for the transition from early to late CD4+ CD8+ thymocytes.

The differentiation process from CD4-CD8- double-negative (DN) thymocytes to CD4+CD8+ double-positive (DP) stage is accompanied by vigorous proliferation. The resulting DP cells contain a sizable proportion of large cycling cells, but most DP cells are small resting cells. To explore the molecular mechanisms which regulate cell proliferation of DP thymocytes prior to further development, we used TCR-transgenic (Tg) mice with non-selecting MHC (Tg-Neut), which contain almost exclusively DP thymocytes that are not subject to either positive or negative selection. In Tg-Neut, the thymus contained DP cells of relatively large size, which showed higher extracellular signal-regulated kinase activity and enhanced responsiveness to mitogen compared to small DP cells. This indicates that all the large DP cells in the thymus are not positively selected and that they possess proliferative potential. When Tg-Neut mice were backcrossed with CD45 knockout mice (CD454-/- Tg-Neut), the thymus showed an increase of large DP cells and cycling cells, but a decrease of apoptotic cells. Furthermore, Bcl-2 expression and Jun N-terminal kinase activity, which are associated with resistance to apoptosis, were enhanced. These observations suggest that thymocyte proliferation in the DP stage is suppressed by a CD45-related process with regulation of mitogen-activated protein kinase and Bcl-2 unless DP cells receive TCR-mediated signals.

Animals↗

Total synthesis of glycononaosyl ceramide with a sialyl dimeric Le(x)-sequence.

The first total synthesis of glycononaosyl ceramide with a sialyl dimeric Le(x) sequence 1 is described. Regio- and stereo-selective glycosylations of sialyl donors 6,7,8 with the suitably protected Le(x) trisaccharide acceptors 9,10 beta were performed to give the expected tetrasaccharides 15 and 21, which were converted into the corresponding donors 20 and 22. Boron trifluoride etherate-promoted glycosylation of 20 with pentasaccharide acceptor 11 afforded regioselectively the expected nonasaccharide 23. After replacing benzyl groups of 23 by acetyl groups, the anomeric acetate was transformed into the alpha-trichloroacetimidate 27. The crucial coupling between 27 and (2S, 3R, 4E-3-O-benzoyl-2-N-tetracosanoylsphingenine 3 was executed to afford completely protected beta-glycoside 28. Finally, selective cleavage of the methyl ester and N,O-deprotection of 28 gave the target ganglioside 1.

Carbohydrate Sequence↗