Proceedings of the Japan Academy, Series B

Reviews

Tubulin-dynein system in flagellar and ciliary movement

Hideo MOHRI, Kazuo INABA, Sumio ISHIJIMA, Shoji A. BABA

2012 Volume 88 Issue 8 Pages 397-415
Published: October 11, 2012
Released on J-STAGE: October 11, 2012

DOIhttps://doi.org/10.2183/pjab.88.397

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Eukaryotic flagella and cilia have attracted the attention of many researchers over the last century, since they are highly arranged organelles and show sophisticated bending movements. Two important cytoskeletal and motor proteins, tubulin and dynein, were first found and described in flagella and cilia. Half a century has passed since the discovery of these two proteins, and much information has been accumulated on their molecular structures and their roles in the mechanism of microtubule sliding, as well as on the architecture, the mechanism of bending movement and the regulation and signal transduction in flagella and cilia. Historical background and the recent advance in this field are described.

(Communicated by Nobutaka HIROKAWA, M.J.A.)

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Structural studies of large nucleoprotein particles, vaults

Hideaki TANAKA, Tomitake TSUKIHARA

2012 Volume 88 Issue 8 Pages 416-433
Published: October 11, 2012
Released on J-STAGE: October 11, 2012

DOIhttps://doi.org/10.2183/pjab.88.416

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Vault is the largest nonicosahedral cytosolic nucleoprotein particle ever described. The widespread presence and evolutionary conservation of vaults suggest important biologic roles, although their functions have not been fully elucidated. X-ray structure of vault from rat liver was determined at 3.5 Å resolution. It exhibits an ovoid shape with a size of 40 × 40 × 67 nm³. The cage structure of vault consists of a dimer of half-vaults, with each half-vault comprising 39 identical major vault protein (MVP) chains. Each MVP monomer folds into 12 domains: nine structural repeat domains, a shoulder domain, a cap-helix domain and a cap-ring domain. Interactions between the 42-turn-long cap-helix domains are key to stabilizing the particle. The other components of vaults, telomerase-associated proteins, poly(ADP-ribose) polymerases and small RNAs, are in location in the vault particle by electron microscopy.

(Communicated by Shigekazu NAGATA, M.J.A.)

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Therapeutic targets in the ASK1-dependent stress signaling pathways

Ryoichi HAYAKAWA, Teruyuki HAYAKAWA, Kohsuke TAKEDA, Hidenori ICHIJO

2012 Volume 88 Issue 8 Pages 434-453
Published: October 11, 2012
Released on J-STAGE: October 11, 2012

DOIhttps://doi.org/10.2183/pjab.88.434

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Apoptosis signal-regulating kinase 1 (ASK1) is a member of the mitogen-activated protein kinase kinase kinase (MAP3K) family that activates downstream MAP kinases (MAPKs), c-Jun N-terminal kinases (JNKs) and p38 MAPKs, in response to various stresses, such as reactive oxygen species (ROS), endoplasmic reticulum (ER) stress, lipopolysaccharide, and calcium overload. Activation of the JNK and p38 pathways induces stress responses such as cell death, differentiation, and the production of inflammatory cytokines. A series of studies using ASK1-deficient mice have indicated that ASK1 plays important roles in many stress-related diseases, including cardiovascular and neurodegenerative diseases, suggesting that small compounds that inhibit ASK1 activity could possibly be used for the amelioration of the development and/or progression of these diseases. In this review, we provide an overview of the pathophysiological roles of ASK1-dependent signaling pathways and discuss the mechanistic basis for how these could serve as potential therapeutic targets.

(Communicated by Takao SEKIYA, M.J.A.)

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Original Article

Intra-abdominal fat area is a predictor for new onset of individual components of metabolic syndrome: MEtabolic syndRome and abdominaL ObesiTy (MERLOT study)

Yoko M. NAKAO, Takashi MIYAWAKI, Shinji YASUNO, Kazuhiro NAKAO, Sachik ...

2012 Volume 88 Issue 8 Pages 454-461
Published: October 11, 2012
Released on J-STAGE: October 11, 2012

DOIhttps://doi.org/10.2183/pjab.88.454

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Supplementary material

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Objective: To investigate the significance of intra-abdominal fat area (IAFA) on new onset of individual components of the metabolic syndrome: high blood pressure, dyslipidemia, or hyperglycemia. Methods: We conducted a longitudinal study using checkup data of a hospital from 1994 to 2010. Of 25,255 subjects, we examined 1,380 Japanese, who underwent computed tomography to measure IAFA and had no metabolic syndrome components at baseline. Results: During 3.6 years of the mean follow-up period, one of metabolic syndrome components occurred in 752 subjects. Of three components, high blood pressure was more prevalent. The multiple Cox regression analysis disclosed that IAFA is significantly associated with onset of metabolic syndrome components (HR: 1.05 per 10 cm², 95%CI: 1.03–1.07). This finding was independent of BMI, and significant even in non-obese individuals with body mass index <25 kg/m². Conclusions: MERLOT study demonstrates that IAFA is an independent predictor for new onset of individual components of the metabolic syndrome, even in non-obese healthy Japanese.

(Communicated by Masanori OTSUKA, M.J.A.)

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Opinion

Happy experience of a medical doctor curing from pancreatic cancer —A 60-day diary—

Yousuke SEYAMA

2012 Volume 88 Issue 8 Pages 462-469
Published: October 11, 2012
Released on J-STAGE: October 11, 2012

DOIhttps://doi.org/10.2183/pjab.88.462

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Pancreatic cancer was found by an abdominal CT scan in a medical doctor, the author of this article, before the appearance of any symptoms. After considering all the imaging findings including the CT, MRI, and PET, a diagnosis was made. He was admitted in the University of Tokyo Hospital on the 14th day after the CT finding. On the 18th day, the operation was successfully performed, and no tumor invading to adjacent tissue was seen. On the 29th day, 11th day after the operation, he left the hospital with a drain still in place to excrete abdominal exudation. The remaining drain was finally removed on the 60th day, and the treatment by the surgeon was completed. The chronological events that occurred during these 60 days are described in diary form. There is nothing superior to early detection and early treatment in the fight against cancer. He recommends everybody to receive periodical medical examinations before praying for good luck.

(Communicated by Takashi SUGIMURA, M.J.A.)

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