1: Multimodal two-photon imaging using a second harmonic generation-specific dye.
Science of the Month - June 2016
Nat Commun.
2016 May 9;7:11557. doi: 10.1038
Mutsuo Nuriya, Shun Fukushima, Atsuya Momotake, Takanori Shinotsuka, Masato Yasui, Tatsuo Arai
Life phenomena occurring on the cell membrane that covers the cell surface and in its vicinity are one of the most important factors governing the function of individual cells and tissues. Therefore, visualizing and measuring cell membrane phenomena holds the key to understanding the normal functioning of cells and the pathological conditions caused by their disruption. Until now, much of the research on cell membranes has been advanced through fluorescence imaging of proteins and dyes, but there have been various problems such as phototoxicity and competition with other fluorescent dyes. On the other hand, observation using a nonlinear optical phenomenon called second harmonic generation (SHG), which is also used in green laser pointers, has been suggested to be very useful for visualizing cell membrane phenomena, but its use in life science research has been rare due to the lack of suitable dyes for observation. To overcome these limitations, this study attempted the development and application of the world's first non-fluorescent, SHG-specific dye. It has become clear that SHG imaging using the newly developed SHG-specific dye Ap3 enables the visualization of cell membrane morphology, the measurement of membrane potential changes, and multimodal two-photon microscopy observation that promotes an integrated understanding of cell physiological functions. Furthermore, due to its low photobleaching and cytotoxicity associated with light irradiation, it is considered suitable for long-term imaging of cell membrane phenomena. The establishment of a new method for quantitatively and long-term analysis of cell membrane phenomena, which were previously difficult to observe, through imaging using this novel SHG-specific dye is expected to greatly accelerate the advancement of cell biology and medical research.
(Mutsuo Nuriya, Department of Pharmacology, equivalent to the Class of '80)
2: SAMD9 mutations cause a novel multisystem disorder, MIRAGE syndrome, and are associated with loss of chromosome 7.
Nat Genet.
2016 May 16. doi: 10.1038/ng.3569.
Narumi S, Amano N, Ishii T, Katsumata N, Muroya K, Adachi M, Toyoshima K, Tanaka Y, Fukuzawa R, Miyako K, Kinjo S, Ohga S, Ihara K, Inoue H, Kinjo T, Hara T, Kohno M, Yamada S,Urano H, Kitagawa Y, Tsugawa K, Higa A, Miyawaki M, Okutani T, Kizaki Z, Hamada H, Kihara M, Shiga K, Yamaguchi T, Kenmochi M, Kitajima H, Fukami M, Shimizu A, Kudoh J, Shibata S, Okano H, Miyake N, Mastumoto N, Hasegawa T.
A research team from the Department of Pediatrics, including Project Assistant Professor Satoshi Narumi (currently at the Department of Molecular Endocrinology, National Center for Child Health and Development, Class of '00), Research Fellow Naoko Amano (Class of '00), Senior Lecturer Tomohiro Ishii (Class of '00), and Professor Toshihiro Hasegawa (equivalent to the Class of '63), analyzed 24 patients with congenital adrenal hypoplasia of unknown cause using next-generation gene sequencers and other methods, identifying SAMD9 mutations in 11 of them. The 11 individuals with SAMD9 mutations shared common symptoms in addition to congenital adrenal hypoplasia, including hematopoietic abnormalities, susceptibility to infection, growth restriction, gonadal phenotypes, and gastrointestinal symptoms. The team confirmed this to be a novel, previously undescribed syndrome and proposed the name MIRAGE syndrome, based on its six main symptoms: Myelodysplasia, Infection, Restriction of growth, Adrenal hypoplasia, Genital phenotypes, and Enteropathy. Furthermore, the research team investigated cell proliferation and found that while wild-type SAMD9 expression causes mild growth suppression, the expression of all identified mutant SAMD9 variants leads to extremely strong growth suppression. In examining the pathology at the cellular level, they revealed an increase in the size of early endosomes in patient-derived cells and the cytoplasmic occupation by giant vesicles expressing late endosome markers. Two patients with MIRAGE syndrome also had myelodysplastic syndrome due to chromosome 7 deletion, which is extremely rare in children, suggesting that the presence of the SAMD9 mutation induced the chromosomal deletion. Chromosomal deletions through a similar mechanism have not been previously reported, and this is an important finding for elucidating the mechanisms of acquiring chromosomal abnormalities in malignant diseases in general.
(Toshihiro Hasegawa, Department of Pediatrics, equivalent to the Class of '63)
Other Published Papers
1: Performance and Validation of the U.S. NCDR Acute Kidney Injury Prediction Model in Japan.
J Am Coll Cardiol
2016 Apr 12;67(14):1715-22. doi: 10.1016/j.jacc.2016.01.049.
Inohara T, Kohsaka S, Miyata H, Ueda I, Maekawa Y, Fukuda K, Cohen DJ, Kennedy KF, Rumsfeld JS, Spertus JA.
2: Quality of diet and mortality among Japanese men and women: Japan Public Health Center based prospective study.
BMJ-BRITISH MEDICAL JOURNAL
352 10.1136/bmj.i1209 MAR 22 2016
Kurotani Kayo, Akter Shamima, Kashino Ikuko, Goto Atsushi, Mizoue Tetsuya, Noda Mitsuhiko, Sasazuki Shizuka, Sawada Norie, Tsugane Shoichiro
3: Coping strategies and risk of cardiovascular disease incidence and mortality: the Japan Public Health Center-based prospective Study
EUROPEAN HEART JOURNAL
37 (11):890-899; 10.1093/eurheartj/ehv724 MAR 14 2016
Svensson Thomas, Inoue Manami, Sawada Norie, Yamagishi Kazumasa, Charvat Hadrien, Saito Isao, Kokubo Yoshihiro, Iso Hiroyasu, Kawamura Noriyuki, Shibuya Kenji, Mimura Masaru, Tsugane Shoichiro