Tokushima, Japan
Tokushima, Japan

Tokushima Bunri University is a private university in Tokushima, Japan. Wikipedia.

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Kasai H.,University of Tokyo | Kasai H.,Tokushima Bunri University | Takahashi N.,University of Tokyo | Takahashi N.,Tokushima Bunri University | And 2 more authors.
Physiological Reviews | Year: 2012

The dynamics of exocytosis are diverse and have been optimized for the functions of synapses and a wide variety of cell types. For example, the kinetics of exocytosis varies by more than five orders of magnitude between ultrafast exocytosis in synaptic vesicles and slow exocytosis in large dense-core vesicles. However, in all cases, exocytosis is mediated by the same fundamental mechanism, i.e., the assembly of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins. It is often assumed that vesicles need to be docked at the plasma membrane and SNARE proteins must be preassembled before exocytosis is triggered. However, this model cannot account for the dynamics of exocytosis recently reported in synapses and other cells. For example, vesicles undergo exocytosis without prestimulus docking during tonic exocytosis of synaptic vesicles in the active zone. In addition, epithelial and hematopoietic cells utilize cAMP and kinases to trigger slow exocytosis of nondocked vesicles. In this review, we summarize the manner in which the diversity of exocytosis reflects the initial configurations of SNARE assembly, including trans-SNARE, binary-SNARE, unitary-SNARE, and cis-SNARE configurations. The initial SNARE configurations depend on the particular SNARE subtype (syntaxin, SNAP25, or VAMP), priming proteins (Munc18, Munc13, CAPS, complexin, or snapin), triggering proteins (synaptotagmins, Doc2, and various protein kinases), and the submembraneous cytomatrix, and they are the key to determining the kinetics of subsequent exocytosis. These distinct initial configurations will help us clarify the common SNARE assembly processes underlying exocytosis and membrane trafficking in eukaryotic cells. © 2012 the American Physiological Society.

Setaka W.,Tokushima Bunri University | Setaka W.,Japan Science and Technology Agency | Yamaguchi K.,Tokushima Bunri University
Journal of the American Chemical Society | Year: 2012

A macrocage molecule with a bridged phenylene rotor has been reported as a molecular gyrotop, because the rotor can rotate even in a crystalline state. Although the most stable cage structure of the molecular gyrotop in a crystal was folded and shrunken at low temperature, expansion of the cage was observed at high temperature due to rapid rotation of the phenylene in a crystal. This phenomenon is analogous to the deflation and inflation of a balloon. Moreover, the unusually large thermal expansion coefficient of the crystal was estimated in the temperature range in which the expansion of the cage was observed, indicating a new function of dynamic states of the molecules. © 2012 American Chemical Society.

Fujiki H.,Tokushima Bunri University | Suganuma M.,Research Institute for Clinical Oncology
Anti-Cancer Agents in Medicinal Chemistry | Year: 2011

Microcystin-LR and nodularin, along with okadaic acid, are potent inhibitors of protein phosphatases 1 and 2A (PP1 and PP2A). The mechanisms of action of microcystin-LR and nodularin in the liver and that of okadaic acid, a potent tumor promoter on mouse skin, have attracted the attention of the scientists. This paper reviews several topics: new inhibitors of PP1 and PP2A with new chemical structures, structure-function relationships for both receptor binding and inhibition of protein phosphatases, the crystal structure of PP1 or PP2A - toxin complex, induction of gene expression and apoptosis. These subjects were studied by using in vitro and in vivo experimental systems. Two-stage carcinogenesis experiments with microcystin-LR and nodularin for the first time demonstrated that microcystin-LR is a new tumor promoter in rat liver initiated with diethylnitrosamine (DEN), and that nodularin is a potent tumor promoter associated with weak initiating activity in rat liver initiated with DEN. A working group of WHO (IARC) concluded that microcystin-LR is "possibly carcinogenic to humans and that nodularin is "not classifiable as to carcinogenicity". Our studies revealed that chemical tumor promoters are inducers of TNF-α in the cells of target tissues and that TNF-α is an endogenous tumor promoter. This advance in carcinogenesis made it possible to look for the link between chemical tumor promoters and endogenous tumor promoters, such as TNF-α and IL-1. The carcinogenic features of TNF-α are described in this review, and the TNF-α inducing protein (Tipα) of Helicobacter pylori genome is presented as an example of a tumor promoter of human stomach cancer development. © 2011 Bentham Science Publishers Ltd.

Suzuki M.,Tokushima Bunri University
Molecules (Basel, Switzerland) | Year: 2012

DNA is constantly exposed to endogenous and exogenous oxidative stresses. Damaged DNA can cause mutations, which may increase the risk of developing cancer and other diseases. G:C-C:G transversions are caused by various oxidative stresses. 2,2,4-Triamino-5(2H)-oxazolone (Oz), guanidinohydantoin (Gh)/iminoallantoin (Ia) and spiro-imino-dihydantoin (Sp) are known products of oxidative guanine damage. These damaged bases can base pair with guanine and cause G:C-C:G transversions. In this study, the stabilization energies of these bases paired with guanine were calculated in vacuo and in water. The calculated stabilization energies of the Ia:G base pairs were similar to that of the native C:G base pair, and both bases pairs have three hydrogen bonds. By contrast, the calculated stabilization energies of Gh:G, which form two hydrogen bonds, were lower than the Ia:G base pairs, suggesting that the stabilization energy depends on the number of hydrogen bonds. In addition, the Sp:G base pairs were less stable than the Ia:G base pairs. Furthermore, calculations showed that the Oz:G base pairs were less stable than the Ia:G, Gh:G and Sp:G base pairs, even though experimental results showed that incorporation of guanine opposite Oz is more efficient than that opposite Gh/Ia and Sp.

Mukai R.,Tokushima Bunri University | Ohshima T.,Tokushima Bunri University
Oncogene | Year: 2014

Human T-cell leukemia virus type-1 (HTLV-1) infection causes adult T-cell leukemia (ATL). Modulation of the transcriptional control of cellular genes by HTLV-1 is thought to be associated with the development of ATL. The viral protein HTLV-1 basic leucine-zipper factor (HBZ) has been shown to dysregulate the activity of cellular transcription factors. Here, we demonstrate that HBZ is exported from the nucleus to the cytoplasm, where it activates the mammalian target of rapamycin (mTOR) signaling pathway through an association with growth arrest and DNA damage gene 34 (GADD34). The N-terminal region of HBZ interacts with the C-terminal region of GADD34. HBZ contains a functional nuclear export signal (NES) sequence within its N-terminal region and it is exported from the nucleus via the CRM1-dependent pathway. Nuclear export of HBZ is essential for its interaction with GADD34 and increased phosphorylation of S6 kinase, which is an established downstream target of the mTOR pathway. Starvation-induced autophagy is significantly suppressed by the overexpression of HBZ. These findings indicate that HBZ is actively exported to the cytoplasm, where it dysregulates the function of cellular factors.

Setaka W.,Tokyo Metroplitan University | Yamaguchi K.,Tokushima Bunri University
Journal of the American Chemical Society | Year: 2013

Successful control of the orientation of the π-electron systems in media has been achieved in certain liquid crystals, making them applicable to devices for optical systems because of the variation in the optical properties with the orientation of the π-electron system. However, because of close packing, changing the orientation of molecules in the crystalline state is usually difficult. A macrocage molecule with a bridged thiophene rotor was synthesized as a molecular gyrotop having a dipolar rotor, given that the dipole derived from the thiophene can rotate even in the crystal. The thermally induced change in the orientation of the dipolar rotors (thiophene ring) inside the crystal, i.e., order-disorder transition, and the variation in the optical properties in the crystalline state were observed. © 2013 American Chemical Society.

For the restricted three-body problem, we propose an accurate orbital integration scheme that retains all conserved quantities of the two-body problem with two primaries and approximately preserves the Jacobi integral. The scheme is obtained by taking the limit as mass approaches zero in the discrete-time general three-body problem. For a long time interval, the proposed scheme precisely reproduces various periodic orbits that cannot be accurately computed by other generic integrators. © 2013. The American Astronomical Society. All rights reserved. Printed in the U.S.A.

Minesaki Y.,Tokushima Bunri University
Astronomical Journal | Year: 2013

We propose an accurate orbital integration scheme for the general three-body problem that retains all conserved quantities except angular momentum. The scheme is provided by an extension of the d'Alembert-type scheme for constrained autonomous Hamiltonian systems. Although the proposed scheme is merely second-order accurate, it can precisely reproduce some periodic, quasiperiodic, and escape orbits. The Levi-Civita transformation plays a role in designing the scheme. © 2013. The American Astronomical Society. All rights reserved.

Minesaki Y.,Tokushima Bunri University
Astronomical Journal | Year: 2013

There is no known integrator that yields exact orbits for the general three-body problem (G3BP). It is difficult to verify whether a numerical procedure yields the correct solutions to the G3BP because doing so requires knowledge of all 11 conserved quantities, whereas only six are known. Without tracking all of the conserved quantities, it is possible to show that the discrete general three-body problem (d-G3BP) yields the correct orbits corresponding to Lagrange solutions of the G3BP. We show that the d-G3BP yields the correct solutions to the G3BP for two special cases: the equilateral triangle and collinear configurations. For the triangular solution, we use the fact that the solution to the three-body case is a superposition of the solutions to the three two-body cases, and we show that the three bodies maintain the same relative distances at all times. To obtain the collinear solution, we assume a specific permutation of the three bodies arranged along a straight rotating line, and we show that the d-G3BP maintains the same distance ratio between two bodies as in the G3BP. Proving that the d-G3BP solutions for these cases are equivalent to those of the G3BP makes it likely that the d-G3BP and G3BP solutions are equivalent in other cases. To our knowledge, this is the first work that proves the equivalence of the discrete solutions and the Lagrange orbits. © 2013. The American Astronomical Society. All rights reserved.

Tori M.,Tokushima Bunri University
Molecules | Year: 2015

The relative stabilities of several cis- and trans-hydrindanones were compared using both isomerization experiments and MM2 calculations. The generally believed rule that cis-hydrindanones are more stable than trans-isomers is applicable, but is not always true. This review introduces examples, mainly from studies in our laboratory, to explain these facts. © 2015 by the authors.

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