Masaya Kato

Y14 Positively Regulates TNF-α–Induced NF-κB Transcriptional Activity via Interacting RIP1 and TRADD Beyond an Exon Junction Complex Protein

Although Y14 is known to be a component of the exon junction complex, we previously reported that Y14 regulates IL-6–induced STAT3 activation. In this study, we showed that endogenous Y14 positively regulated TNF-α–induced IL-6 expression in HeLa cells. Small interfering RNA–mediated Y14-knockdown reduced TNF-α–induced and NF-κB–mediated transcriptional activity, phosphorylation/degradation of IκBα, and nuclear localization of NF-κB/p65. As in the case of IL-6 stimuli, Y14 enhanced TNF-α–induced STAT3 phosphorylation, which is important for its nuclear retention. However, our manipulation of Y14 expression indicated that it is involved in TNF-α–induced IL-6 expression via both STAT3-dependent and -independent mechanisms. We screened signaling molecules in the TNF-α–NF-κB pathway and found that Y14 endogenously associated with receptor-interacting protein 1 (RIP1) and TNFR-associated death domain (TRADD). Overexpression of RIP1, but not TRADD, restored TNF-α–induced NF-κB activation in Y14-knockdown cells, and Y14 overexpression restored TNF-α–induced NF-κB activation in TRADD-knockdown cells, but not in RIP1-knockdown cells, indicating that Y14 lies downstream of TRADD and upstream of RIP1. Of importance, Y14 significantly enhanced the binding between RIP1 and TRADD, and this is a possible new mechanism for Y14-mediated modification of TNF-α signals. Although Y14 associates with MAGOH in the exon junction complex, Y14’s actions in the TNF-α–NF-κB pathway are unlikely to require MAGOH. Therefore, Y14 positively regulates signals for TNF-α–induced IL-6 production at multiple steps beyond an exon junction complex protein.

Mechanism of the inhibitory effect of imipramine on the Na+-dependent transport of l-glutamic acid in rat intestinal brush-border membrane

The mechanism of the inhibitory effect of imipramine, a lipophilic organic cation on the Na+-dependent transport of L-glutamic acid across intestinal brush-border membrane was investigated. The uptake of L-glutamic acid by intestinal brush-border membrane vesicles was dependent on the concentration of Na+. Fitting of the uptake data in the presence of various concentrations of Na+ using Hill equation yielded a Hill coefficient of 2.18. This result suggest that the carrier system of L-glutamic acid has at least two sites for Na+-binding. By the analysis of double reciprocal plot and Dixon-type plot, it was found that imipramine inhibits the transport of L-glutamic acid by interacting competitively with the binding sites of Na+, but not inhibit L-glutamic acid binding site. Moreover, the effect of imipramine on the transport of L-alanine and D-glucose which are co-transported with only one Na+ molecule was also suggestive of interaction with the Na+-binding sites on the carrier. These results indicate that the mechanism of the inhibitory effect of imipramine on the Na+-dependent carrier systems is common for all systems regardless of the stoichiometry or substrates.

PML suppresses IL-6-induced STAT3 activation by interfering with STAT3 and HDAC3 interaction.

The promyelocytic leukemia protein PML acts as a tumor suppressor by forming transcription-regulatory complexes with a variety of repressor proteins. In the present study, we found that endogenous PML suppresses interleukin (IL)-6-induced gene expression as well as phosphorylation and transcriptional activation of STAT3 in hepatoma cells. We also found that PML-mediated suppression of IL-6-induced STAT3 activation by disrupting interactions between STAT3 and HDAC3. These results indicate that PML modulates IL-6-induced STAT3 activation and hepatoma cell growth by interacting with HDAC3.

Report on the 2014 Winter Cyclone Storm Surge in Nemuro, Japan

From Tuesday, 16 December 2014, until Thursday, 18 December 2014, Hokkaido was battered by strong winds and high sea waves caused by a passing low pressure system intensified to typhoon levels. In the city of Nemuro, a rise in sea level influenced by the storm surge which exceeded quay height in port areas was observed from predawn Wednesday, 17 December 2014. Flooding was experienced in areas of central Nemuro, the Nemuro Port and estuaries of rivers. This technical note provides a comprehensive meteorological analysis and the results of a local flood survey carried out by the authors from 19 to 21 December 2014, and summarizes the characteristics of the 2014 Nemuro storm surge disaster.

WAVE CONTROL BY A FLOATING STRUCTURE WITH ELASTIC DEFORMATION

In marinas, a type of floating structure composed by joined floating units is used for a breakwater or pier. Kato et al (2001) discussed the wave control effects by such a structure in the case of normalincident waves.But generally, the incident waves propagate obliquely toward the structure. In this case, the wave force is notuniform along the structure. Therefore the structure elastically vibrate with this un-uniform force. In thepresent paper, we analyze the wave field and the elastic vibration of the floating structure, and discuss thewave control effects and the interaction between the wave field and the motion of structure.

Large-Eddy Simulation of Local Flows around the Head of a Breakwater

In this study, three-dimensional fluid motion in waves around the head of a semi-infinite vertical breakwater was investigated using large-eddy simulation (LES). Wave deformation, separation, and evolution of vortices were investigated to obtain basic data in order to develop a reliable model for predicting local scouring and for estimating local fluid forces acting on the structure. Moreover, the processes by which separated eddies are generated and evolved were discussed in detail in order to determine the mechanisms by which the separated vortices cause local failures of armor blocks and the mound of a breakwater. Two significant vertical separations appeared around both edges of the breakwater head, especially when the wave front passed each edge. The velocity field around the head of the breakwater became significantly three-dimeusional because secondary horizontal and helical eddies arose due to the vertical gradient of shear associated with the vertical separation. Furthermore, during interactions among these eddies, a complex three-dimensional eddy structure was formed around the head of the breakwater. It is possible that the vertical velocity caused by the threedimensional eddy structure is associated with the suspension of sediment around the structure. INTRODUCTION A composite breakwater consists of a concrete caisson as the vertical wall and a rubble mound foundation. There are several reports concerning damages to the breakwater. Takahashi et al. (2000) classified typical failures of composite breakwaters 1 Senior Research Engineer, Nippon Data Service Co., Ltd., Kita-16 Higashi-19, Sapporo 065-0016, JAPAN, kato@kowanws2.hyd.eng.hokudai.ac.j p 2 Graduate Student, Offshore & Coastal Engineering Lab., Graduate School of Eng., Hokkaido University, Kita-13 Nishi-8, Sapporo 060-8628, JAPAN, okumura@kowanws2.hyd.eng.hokudai.ac.jp 3 Assistant Professor, Offshore & Coastal Engineering Lab., Graduate School of Eng., Hokkaido University, Kita-13 Nishi-8, Sapporo 060-8628, JAPAN, yasunori@eng.hokudai.ac.jp 4 Professor, Offshore & Coastal Engineering Lab., Graduate School of Eng., Hokkaido University, Kita13 Nishi-8, Sapporo 060-8628, JAPAN, h-saeki@eng.hokudal.ac.jp