伝統的事業ｼｽﾃﾑの競争優位と課題 -堺･関･燕の刃物産業の比較より-

本研究は､伝統産業の1つである刃物産業に焦点をあて､その事業ｼｽﾃﾑの競争優位を分析することにより､さらになる成長を実現するためには何が必要かを明らかにしようとした研究である｡そのため､堺･関･燕の主として包丁を製造する企業や個人事業主にｲﾝﾀﾋﾞｭｰ調査を行った｡調査の結果､①堺は問屋を中心とした分業体制により発展してきたが､調整役である問屋の求心力が弱くなり､その体制が崩れてきたこと､②洋包丁の産地である関や燕は､合理性や柔軟性といった特徴が規模の経済と速度の経済､範囲の経済を発揮し､競争優位につながっていること､④各産地間では積極的にOEM生産が行われ､刃物産業全体の衰退を防いでいる可能性があること､⑤伝統産業は技術とﾌﾞﾗﾝﾄﾞが強みであるが､それが制約となり､成長機会を逃す可能性があり､企業の長期的成長を考えた場合､伝統と革新のﾊﾞﾗﾝｽが課題となることが明らかとなった｡This study investigates the competitive advantage of the business system of the kitchen knife industry, which is one of the most popular traditional industries, for their further growth. We had an interview with managers and owners of the companies producing kitchen knives in Sakai, Seki and Tsubame in Japan. The results of this research are below. (1)Companies in Sakai have produced Japanese style kitchen knives by using the system of specialization of manufacturers, which is coordinated by wholesalers. But this system has been disintegrating with a decrease of coordination power of wholesalers. (2)Companies in Seki and Tsubame, which have produced western style kitchen knives, have the rationality and the flexibility to achieve economies of scale, speed and scope, leading to their competitive advantage. (3)They use OEM(original equipment manufacturing)trade among their industrial clusters to avoid the decline of the knife and cutlery industry in Japan. (4)Although they have core skills and strong brands, they have missed an opportunity for growth because of their own strength. Thus, it is suggested that keeping the balance of tradition and innovation is the key to achieving long-term growth

Kaposi's sarcoma-associated herpesvirus-encoded LANA associates with glucocorticoid receptor and enhances its transcriptional activities

Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded latency-associated nuclear antigen (LANA), which interacts with cellular proteins, plays a central role in modification of viral and/or cellular gene expression. Here, we show that LANA associates with glucocorticoid receptor (GR), and that LANA enhances the transcriptional activity of GR. Co-immunoprecipitation revealed a physical interaction between LANA and GR in transiently transfected 293T and HeLa cells. In human B-lymphoma cells, LANA overexpression enhanced GR activity and cell growth suppression following glucocorticoid stimulation. Furthermore, confocal microscopy showed that activated GR was bound to LANA and accumulated in the nucleus, leading to an increase in binding of activated GR to the glucocorticoid response element of target genes. Taken together, KSHV-derived LANA acts as a transcriptional co-activator of GR. Our results might suggest a careful use of glucocorticoids in the treatment of patients with KSHV-related malignancies such as Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman disease. (C) 2015 Elsevier Inc. All rights reserved

Fingolimod (FTY720) Stimulates Ca²⁺/Calcineurin Signaling in Fission Yeast

<div><p>Fingolimod hydrochloride (FTY720) is the first in class of sphingosine 1-phosphate (S1P) receptor modulator approved to treat multiple sclerosis via down-regulation of G protein-coupled S1P receptor 1 by its phosphorylated form (FTY720-P). Many studies have revealed that FTY720 exerts various biological effects, including antitumor activities, angiogenesis inhibition, Ca²⁺ mobilization and apoptosis, independently of S1P receptors. However, the exact mechanisms underlying their effects or signaling pathways mediated by FTY720 have not been completely established. To gain further insights into molecular mechanisms of FTY720 action, the effect of FTY720 on Ca²⁺ signaling in fission yeast was analyzed. The addition of Ca²⁺ enhanced the sensitivity induced by FTY720, and mutants lacking genes required for calcium homeostasis, including calcineurin and its downstream transcription factor, <u>P</u>pb1-<u>r</u>esponsive zinc finger protein (Prz1), were hypersensitive to FTY720 and CaCl₂. The effect of FTY720 on calcineurin signaling was monitored by utilizing a luciferase reporter construct fused to three tandem repeats of the calcineurin-dependent response element (CDRE), which gives an accurate measure of calcineurin activity. The addition of FTY720 increased calcineurin activity as well as Ca²⁺ influx in a concentration-dependent manner. Notably, the FTY720-mediated Ca²⁺ influx and calcineurin activation were reduced markedly by the deletion of <i>yam8</i>⁺ or <i>cch1</i>⁺ encoding putative subunits of a Ca²⁺ channel. Consistently, the deletion of Pmk1 mitogen-activated protein kinase (MAPK), which plays an important role in the activation of the Yam8/Cch1 channel, markedly decreased the intracellular Ca²⁺ levels upon FTY720 treatment. These results suggest that the FTY720-stimulated Ca²⁺/calcineurin signaling activation partly involves the Yam8/Cch1 channel in fission yeast.</p> </div

Pmk1 MAP kinase activated the FTY720-induced Ca²⁺ influx.

<p>(A) Knockout of Pmk1 MAP kinase suppressed the FTY720-induced Ca²⁺ influx. WT and Δ<i>pmk1</i> cells were monitored as described in the legend of <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081907#pone-0081907-g004" target="_blank">Figure 4 (A)</a>. (B) Knockout of Pmk1 MAP kinase suppressed the FTY720-induced calcineurin signaling. WT and Δ<i>pmk1</i> cells were monitored as described in the legend of <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081907#pone-0081907-g003" target="_blank">Figure 3 (B)</a>. </p

FTY720 stimulates Ca²⁺/calcineurin signaling via the Yam8/Cch1 channel.

<p>(A) The wild-type (wt), Δ<i>yam8</i>, Δ<i>cch1</i>, or Δ<i>yam8</i>Δ<i>cch1</i> cells harboring pKB6892 (<i>adh1</i>-GFP-19-AEQ) were treated with 10 μM FTY720 or vehicle (basal), and the experiments were performed as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081907#pone-0081907-g004" target="_blank">Figure 4 (A)</a>. The histogram was calculated as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081907#pone-0081907-g004" target="_blank">Figure 4 (A)</a>. Bars, SD. (B) Effects of GdCl₃ on the FTY720-induced increase in the cytoplasmic Ca²⁺ level. The experiments were performed as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081907#pone-0081907-g004" target="_blank">Figure 4 (A)</a>, except that 1 mM or 10 mM of GdCl₃ were also added to the EMM medium. The histogram was calculated as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081907#pone-0081907-g004" target="_blank">Figure 4A</a>. (C) Deletion of Yam8 or Cch1 reduced markedly calcineurin activation induced by FTY720. The wild-type (wt), Δ<i>yam8</i>, Δ<i>cch1</i>, or Δ<i>yam8</i>Δ<i>cch1</i> cells harboring the reporter plasmid (wt 3×CDRE::luc(R2.2)) were monitored as described in the legend of <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081907#pone-0081907-g003" target="_blank">Figure 3(B)</a>.　(D) Deletion of Yam8 or Cch1 enhanced the sensitivity to FTY720. A serial dilution assay of the wild-type (wt), Δ<i>yam8</i>, Δ<i>cch1</i>, and Δ<i>yam8</i>Δ<i>cch1</i> mutant cells grown in rich YPD medium containing the indicated concentrations of FTY720. </p

Phosphorylated FTY720 (FTY720-P) failed to stimulate

<p>Ca²⁺/calcineurin signaling. (A) Effect of FTY720 and FTY720-P on intracellular Ca²⁺ levels. The wild-type cells harboring <i>adh1</i>-GFP-19-AEQ were treated with indicated concentrations of FTY720 or FTY720-P, and experiments were performed as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081907#pone-0081907-g004" target="_blank">Figure 4(A)</a>. Ethanol containing NaOH was used as vehicle (Materials and Methods). The histogram was calculated as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081907#pone-0081907-g004" target="_blank">Figure 4 (A)</a>. Bars, SD. (B) A serial dilution assay of the wild-type (wt) cells grown in rich YPD medium containing the indicated concentrations of FTY720 or FTY720-P. (C) Left: Real-time monitoring of calcineurin activity in living cells stimulated by FTY720 or FTY720-P. Wild-type cells harboring the multicopy plasmid (wt 3xCDRE::luc(R2.2)) reporter vector, pKB5723 (wt 3xCDRE) were treated as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081907#pone-0081907-g003" target="_blank">Figure 3(B)</a>. The data shown are representative of multiple experiments. Right: Graph shows the peak heights of 3xCDRE::luc(R2.2) reporter activity. The data were averaged from three independent experiments. Bars, SD. (D) The effect of FTY720-P induced rise of intracellular Ca²⁺ levels in ABC transporter knockout cells. The wt or Δ<i>bfr1</i>Δ<i>pmd1</i> cells harboring <i>adh1</i>-GFP-19-AEQ were treated with indicated concentrations of FTY720-P, and experiments were performed as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081907#pone-0081907-g004" target="_blank">Figure 4(A)</a>. ** p<0.01; Significantly different from vehicle (using two-way ANOVA). ## p<0.01; Significantly different from wild-type cells (using Williams’ test).</p

Fission yeast sensitivity to FTY720.

<p>(A) Fission yeast cells are sensitive to FTY720. A serial dilution assay of the wild-type strain grown in YPD medium or YPD medium containing the indicated concentrations of FTY720 in the absence (Left: YPD) or presence (Right: + 100 mM CaCl₂) of 100 mM CaCl₂. 　Cells were incubated for 3 days at 27°C. (B) Quantitative measurements of cell growth in the presence of FTY720. The cells were grown in liquid YES cultures to an OD₆₆₀ of 0.3 and were treated with the drugs (FTY720) at the concentrations indicated, and the quantitative measurements of cell growth rates were performed using a microplate reader (Sunrise^TM series, Tecan, Switzerland). A representative for three independent curves is presented. (C) Addition of CaCl₂ exacerbated the fission yeast sensitivity to FTY720. Wild-type cells were cultured in YES liquid medium and treated with 100 mM CaCl₂ in the absence or presence of indicated concentrations of FTY720, and the growth curve of the cells were shown by measuring OD₆₆₀ for 10 h. (D) Graph shows the OD₆₆₀ at 10 h of the cells, as indicated in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081907#pone-0081907-g001" target="_blank">Figure 1(B) and (C)</a>. The data were averaged from three independent experiments. Bars, SD.</p