A minor role of WNK3 in regulating phosphorylation of renal NKCC2 and NCC co-transporters in vivo

Mutations in WNK1 and WNK4 kinase genes have been shown to cause a human hereditary hypertensive disease, pseudohypoaldosteronism type II (PHAII). We previously discovered that WNK kinases phosphorylate and activate OSR1/SPAK kinases that regulate renal SLC12A family transporters such as NKCC2 and NCC, and clarified that the constitutive activation of this cascade causes PHAII. WNK3, another member of the WNK kinase family, was reported to be a strong activator of NCC/NKCC2 when assayed in Xenopus oocytes, suggesting that WNK3 also plays a major role in regulating blood pressure and sodium reabsorption in the kidney. However, it remains to be determined whether WNK3 is in fact involved in the regulation of these transporters in vivo. To clarify this issue, we generated and analyzed WNK3 knockout mice. Surprisingly, phosphorylation and expression of OSR1, SPAK, NKCC2 and NCC did not decrease in knockout mouse kidney under normal and low-salt diets. Similarly, expression of epithelial Na channel and Na/H exchanger 3 were not affected in knockout mice. Na(+) and K(+) excretion in urine in WNK3 knockout mice was not affected under different salt diets. Blood pressure in WNK3 knockout mice was not lower under normal diet. However, lower blood pressure was observed in WNK3 knockout mice fed low-salt diet. WNK4 and WNK1 expression was slightly elevated in the knockout mice under low-salt diet, suggesting compensation for WNK3 knockout by these WNKs. Thus, WNK3 may have some role in the WNK-OSR1/SPAK-NCC/NKCC2 signal cascade in the kidney, but its contribution to total WNK kinase activity may be minimal

バレーボールゲームにおけるボール接触数と勝敗の関係についてIII : 関東大学男子リーグを対象として

We reported two studies on the relationship between the number of ball contact and the results of volleyball games before the alteration of rules in 1999. The purpose of this study is to clarify the relationship between the number of ball contact and the results of the games, as well as why the number of ball contact differs from team to team after the alteration of rules in 1999. This study examined the ball contact recorded on videotape during the game of Kanto Intercollegiate Men\u27s Volleyball League games in 2006. The results of research are as follows : 1) It was confirmed that the team which won a set had lower number of ball contacts as well as the last time. 2) It was confirmed that the team which won a set had lower number of receive contacts. 3) It was confirmed that the team which lost a set had lower points of serve, block and attack. 4) The team which lost a set had lower points in all items of attack points. CAP and CAR accounted for 71%

バレーボールゲームにおけるボール接触数と勝敗の関係についてIV : 東北大学男子リーグ戦を対象として

We tried to inspect the relationship between the number of ball contact and the results of volleyball games in the case of the Tohoku Intercollegiate Men\u27s Volleyball League Matches.The purpose of this study is to clarify the relationship between the number of ball contact and the results of the games, as well as why the number of ball contact differs from team to team.This study examined the ball contact recorded on videotape during the game of Tohoku Intercollegiate Men\u27s Volleyball League games in 2007

Chemopreventive effects and anti-tumorigenic mechanisms of Actinidia arguta, known as sarunashi in Japan toward 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)- induced lung tumorigenesis in a/J mouse

Background Previously, we reported the inhibitory effect of Actinidia arguta juice, known as sarunashi juice (sar-j) in Japan, on mutagenesis, inflammation, and mouse skin tumorigenesis. The components of A. arguta responsible for the anti-mutagenic effects were identified to be water-soluble, heat-labile phenolic compounds. We proposed isoquercetin (isoQ) as a candidate anticarcinogenic component. In this study, we sought to investigate the chemopreventive effects of A. arguta juice and isoQ on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in A/J mice, and identify the possible mechanisms underlying the anti-tumorigenic effects of A. arguta. Results The number of tumor nodules per mouse lung in the group injected with NNK and administered A. arguta juice orally was significantly lower than that in the group injected with NNK only. Oral administration of isoQ also reduced the number of nodules in the mouse lungs. As expected, the mutagenicity of NNK and 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) detected using S. typhimurium TA1535 decreased in the presence of sar-j. However, NNK and MNNG mutagenicity detected using S. typhimurium YG7108, a strain lacking the O6-methylguanine DNA methyltransferases (ogtST and adaST) did not decrease in the presence of sar-j suggesting that sar-j may mediate its antimutagenic effect by enhancing the DNA damage repair by ogtST and adaST. Phosphorylation of Akt, with or without epidermal growth factor stimulation, in A549 cells was significantly decreased following sar-j and isoQ treatment, indicating that components in sar-j including isoQ suppressed the PI3K/AKT signaling pathways. Conclusions Sar-j and isoQ reduced NNK-induced lung tumorigenesis. Sar-j targets both the initiation and growth/progression steps during carcinogenesis, specifically via anti-mutagenesis, stimulation of alkyl DNA adduct repair, and suppression of Akt-mediated growth signaling. IsoQ might contribute in part to the biological effects of sar-j via suppression of Akt phosphorylation, but it may not be the main active ingredient

ガッコウ ニオイテ ジコ シンライシン ジシン オ イクセイ スル ユニバーサル ヨボウ キョウイク : キョウイク プログラム ノ ジッサイ

As introduced by Yamasaki, Sasaki, Uchida, Katsuma, and Matsumoto（2011）, a universal preventive education named “TOP SELF”（Trial Of Prevention School Education for Life and Friendship）has been developed under the science of prevention education. Sasaki and Yamasaki（2012）presented the educational purposes and their scientific evidences for one of the comprehensive base education, development of self−confidence. This educational program consists of eight 45−minute lessons. This paper especially introduced the educational methods for 4th−grade children at elementary schools in detail. It also provided the implementation manuals for school teachers. School teachers are expected to implement this educational program for promoting children’s well−being

ガッコウ ニオイテ ジコ シンライシン ジシン オ イクセイ スル ユニバーサル ヨボウ キョウイク : キョウイク モクヒョウ ノ コウセイ ト ソノ エビデンス

As introduced by Yamasaki, Sasaki, Uchida, Katsuma, & Matsumoto(2011), a universal preventive education named "TOP SELF" (Trial Of Prevention School Education for Life and Friendship) has been developed in the science of preventive education. This paper focused on "development of self−confidece" that is one of the comprehensive base education and aims to develop autonomy. First, the previous educational programs in order to enhance self−confidence or self−esteem were reviewed and the unsolved problems were mentioned. Second, the definition of "self−confidence" in TOP SELF was given. Third, the hierarchical educational purposes for development of self−confidence (constituent, intermediate, subordinate, and operational purposes) were explained in detail with the theoretical background and the scientific evidence. Since the comprehensive base education is planned to implement for the third−graders in elementaly schools to the first−graders in junior high schools in Japan, the educational purposes in each grade were also proposed