Short stature-related single-nucleotide polymorphism (SNP) activates endothelial repair activity in elderly Japanese

Background: Hypertension and atherosclerosis are bidirectionally related, while platelet count could serve as an indicator of endothelial repair. Therefore, high platelet counts could be associated with hypertension by indicating more intense endothelial repair activity. Furthermore, short stature has been shown to constitute a risk of atherosclerosis. Since inflammation-related single-nucleotide polymorphism (SNP(rs3782886)) is reportedly associated with myocardial infarction and short stature, rs3782886 could be associated with a high platelet count and thus more intense endothelial repair activity. Methods: We conducted a cross-sectional study of 988 elderly Japanese who participated in a general health check-up. Short stature was defined as a height of at or under the 25th percentile of the study population, and high platelet count as the highest tertiles of the platelet levels. Results: High platelet counts were found to be independently and positively associated with hypertension while rs3782886 was independently associated with high platelet levels and short stature. The classical cardiovascular risk factor-adjusted odds ratio (OR) and 95% confidence interval (CI) of high platelet count for hypertension was 1.34 (1.02, 1.77). With non-minor homo of the rs3782886 as the reference group, the adjusted OR and 95% CI for high platelet count and short stature of minor home were 2.40 (1.30, 4.42) and 2.21 (1.16, 4.21), respectively. Conclusion: SNP (rs3782886) was shown to be associated with high platelet count and short stature. This result partly explains how a genetic factor can influence the impact of height on endothelial repair

Conditional deletion of Npt2b in phosphate transport

Background Hyperphosphatemia is common in chronic kidney disease and is associated with morbidity and mortality. The intestinal Na+-dependent phosphate transporter Npt2b is thought to be an important molecular target for the prevention of hyperphosphatemia. The role of Npt2b in the net absorption of inorganic phosphate (Pi), however, is controversial. Methods In the present study, we made tamoxifen-inducible Npt2b conditional knockout (CKO) mice to analyze systemic Pi metabolism, including intestinal Pi absorption. Results Although the Na+-dependent Pi transport in brush-border membrane vesicle uptake levels were significantly decreased in the distal intestine of Npt2b CKO mice compared with control mice, plasma Pi and fecal Pi excretion levels were not significantly different. Data obtained using the intestinal loop technique showed that Pi uptake in Npt2b CKO mice was not affected at a Pi concentration of 4 mM, which is considered the typical luminal Pi concentration after meals in mice. Claudin, which may be involved in paracellular pathways, as well as claudin-2, 12, and 15 protein levels were significantly decreased in the Npt2b CKO mice. Thus, Npt2b deficiency did not affect Pi absorption within the range of Pi concentrations that normally occurs after meals. Conclusion These findings indicate that abnormal Pi metabolism may also be involved in tight junction molecules such as Cldns that are affected by Npt2b deficiency

Characterization of the interaction of influenza virus NS1 with Akt

Avian influenza viruses belong to the genus influenza A virus of the family Orthomyxoviridae. The influenza virus consists of eight segmented minus stranded RNA that encode 11 known proteins. Among the 11 viral proteins, NS1 (non-structural protein 1, encoded on segment 8) has been implicated in the regulation of several important intra-cellular functions. In this report, we investigated the functional interaction of NS1 with serine threonine kinase Akt, a core intra-cellular survival regulator. In co-immunoprecipitation assays and GST pull-down assays, NS1 directly interacted with Akt. The interaction was mediated primarily through the Akt-PH (Pleckstrin Homology) domain and the RNA-binding domain of NS1. NS1 preferentially interacted with phosphorylated Akt, but not with non-phosphorylated Akt. Functionally, the NS1-Akt interaction enhanced Akt kinase activity both in the intra-cellular context and in in vitro Akt kinase assays. Confocal microscopic analysis revealed that phosphorylated Akt interacted with NS1 during the interphase of the cell cycle predominantly within the nucleus. Finally, mass spectrometric analysis demonstrated the position at Thr215 of NS1 protein is primary phosphorylation target site through Akt activation. The results together supported the functional importance of influenza virus NS1 with Akt, a core intra-cellular survival regulator

Inhibition of Akt kinase activity suppresses entry and replication of influenza virus

The possibility of the pandemic spread of influenza viruses highlights the need for an effective cure for this life-threatening disease. Influenza A virus, belonging to a family of orthomyxoviruses, is a negative-strand RNA virus which encodes 11 viral proteins. A numbers of intracellular signaling pathways in the host cells interact with influenza the viral proteins, which affect various stages of viral infection and replication. In this study, we investigated how inhibition of Akt kinase activity impacts on influenza virus infection by using "Akt-in", a peptide Akt inhibitor. In PR8 influenza-infected A549 cells, Akt interacted with the NS1 (Non structural protein 1), and hence increased phosphorylation of Akt kinase activity and NS1. Treatment of cells with either "TCL1- or TCL1b-based Akt-in" efficiently suppressed Akt kinase activity while decreasing the levels of phosphorylated NSI; this, in turn, inhibited viral replication in a dose- and time-dependent manner. The inhibitory effect on viral replication appears to not be due to inhibition of the production of inflammatory cytokines, including IL-6 and IL-8, in the host cells. Inhibition of Akt kinase activity in the host cells inhibited the efficiency of viral entry, which is associated with decreased levels of phosphorylated glycogen synthase kinase 3, a substrate of Ala. Thus inhibition of Akt kinase activity in host cells may have therapeutic advantages for influenza virus infection by inhibiting viral entry and replication. (C) 2014 The Authors. Published by Elsevier Inc

The E3 Ligase TTC3 Facilitates Ubiquitination and Degradation of Phosphorylated Akt

The serine threonine kinase Akt is a core survival factor that underlies a variety of human diseases. Although regulatory phosphorylation and dephosphorylation have been well documented, the other post-translational mechanisms that modulate Akt activity remain unclear. We show herein that TTC3 (tetratricopeptide repeat domain 3) is an E3 ligase that interacts with Akt. TTC3 contains a canonical RING-finger motif, a pair of TPR (tetratricopeptide) motifs, a putative Akt phosphorylation site, and nuclear localization signals, and is encoded by a gene within the Down Syndrome (DS) Critical Region on chromosome 21. TTC3 is an Akt-specific specific E3 ligase that binds to phosphorylated Akt and facilitates its ubiquitination and degradation within the nucleus. Moreover, DS cells exhibit elevated TTC3 expression, reduced phosphorylated Akt, and accumulation in the G2M phase, which can be reversed by TTC3 siRNA or Myr-Akt. Thus, interaction between TTC3 and Akt may contribute to the clinical symptoms of DS

First report of Magnificent Bryozoan Pectinatella magnifica（LEIDY） in Wakayama Prefecture and its distribution at Kinokawa and Iwade Cities

[要旨]北アメリカを原産地とするオオマリコケムシPectinatella magnifica はわが国では1972年に山梨県の河口湖で初めて確認され、翌1973年には同県精進湖で多数の群体塊が出現し、世間の注目を集めるところとなった。その後は日本各地に分布を広げ、水中に生息する大きな塊をした奇妙な外来種として知られるようになったが、和歌山県内での発見報告は今までなかった。2012年8月、近畿大学生物理工学部キャンパスの西端に位置する池で本種と思われる群体塊を発見し、大きさ、形態を詳しく観察してオオマリコケムシと同定し、和歌山県での初確認とした。さらにこの周辺の湖沼における分布を調査した。2012年8 月から2013年1月までの間、紀の川市・岩出市の湖沼56 か所の水面、水中を目視のみで群体塊の有無を確認した。2013 年8月から2014 年1月までの間は、同地域の湖沼110 か所（前年に調査した56か所すべてを含む）を目視に加えて、水面上をネットですくい取りし、浮遊する直径約１㎜大のスタトブラストの存在を確認する方法も併用して行った。その結果、24 か所で本種の分布が確認された。 [Abstract] The freshwater Magnificent Bryozoan, Pectinatella magnifica, a confirmed native invertebrate of North America, was identified in Lake Kawaguchiko, Yamanashi Prefecture, Japan in 1972. A large number of Magnificent Bryozoan colonies appeared in Lake Shojinko in 1973, and as a result, came to attract attention. It spread widely in various regions of Japan and this strange, large, lumpy, naturalized water species came to be widely known. There had been no reported discoveries in Wakayama to date. In August, 2012, we discovered a group of colonies, which we believe to be bryozoans, in a pond located at the west end of the Wakayama Campus of Kinki University and we observed their size and form, and identified them as the first Pectinatella magnifica in Wakayama Prefecture. Furthermore, we investigated the distribution in neighboring ponds. We visually confirmed the surface of the water of 56 spots in ponds in Kinokawa and Iwade cities, and confirmed the existence of these colonies from August, 2012 to January, 2013. We confirmed sightings at 110 spots（including 56 which we had investigated last year）in the area in which we visually confirmed from August, 2013 to January, 2014 and caught some on the surface of the water using a plankton net and used this method to confirm the existence of statoblasts, of approximately 1mm diameter in size, floating together. As a result, the distribution of Magnificent Bryozoans was confirmed in 24 out of 110 spots of ponds that we investigated.近畿大学先端技術総合研究所紀要編集委員

Generation of two human induced pluripotent stem cell lines derived from two X-linked adrenoleukodystrophy patients with ABCD1 mutations

Adrenoleukodystrophy (ALD) is an X-linked genetic disorder, characterized by demyelination in the central nervous system and adrenal insufficiency. Human induced pluripotent stem cell (hiPSC) lines derived from two Japanese male patients with ALD were generated from skin fibroblasts using retroviral vectors. The generated hiPSC lines showed self-renewal and pluripotency, and carried either a missense or a nonsense mutation in ABCD1 gene. Since the molecular pathogenesis caused by ABCD1 dysfunction remains unclear, these cell resources provide useful tools to establish disease models and to develop new therapies for X-ALD