Proceedings of the Japan Academy, Series B
Online ISSN : 1349-2896
Print ISSN : 0386-2208
ISSN-L : 0386-2208
Volume 93 , Issue 9
Showing 1-6 articles out of 6 articles from the selected issue
Reviews
  • Yuki HITOMI, Katsushi TOKUNAGA
    2017 Volume 93 Issue 9 Pages 657-676
    Published: November 10, 2017
    Released: November 10, 2017
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    Human genome variation may cause differences in traits and disease risks. Disease-causal/susceptible genes and variants for both common and rare diseases can be detected by comprehensive whole-genome analyses, such as whole-genome sequencing (WGS), using next-generation sequencing (NGS) technology and genome-wide association studies (GWAS). Here, in addition to the application of an NGS as a whole-genome analysis method, we summarize approaches for the identification of functional disease-causal/susceptible variants from abundant genetic variants in the human genome and methods for evaluating their functional effects in human diseases, using an NGS and in silico and in vitro functional analyses. We also discuss the clinical applications of the functional disease causal/susceptible variants to personalized medicine.

  • Makoto MURAKAMI
    2017 Volume 93 Issue 9 Pages 677-702
    Published: November 10, 2017
    Released: November 10, 2017
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    The phospholipase A2 (PLA2) family comprises a group of lipolytic enzymes that typically hydrolyze the sn-2 position of glycerophospholipids to give rise to fatty acids and lysophospholipids. The mammalian genome encodes more than 50 PLA2s or related enzymes, which are classified into several subfamilies on the basis of their structures and functions. From a general viewpoint, the PLA2 family has mainly been implicated in signal transduction, producing bioactive lipid mediators derived from fatty acids and lysophospholipids. Recent evidence indicates that PLA2s also contribute to phospholipid remodeling for membrane homeostasis or energy production for fatty acid β-oxidation. Accordingly, PLA2 enzymes can be regarded as one of the key regulators of the quality of lipids, which I herein refer to as lipoquality. Disturbance of PLA2-regulated lipoquality hampers tissue and cellular homeostasis and can be linked to various diseases. Here I overview the current state of understanding of the classification, enzymatic properties, and physiological functions of the PLA2 family.

  • Shuntaro HARA
    2017 Volume 93 Issue 9 Pages 703-723
    Published: November 10, 2017
    Released: November 10, 2017
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    Non-steroidal anti-inflammatory drugs (NSAIDs) exert their anti-inflammatory and anti-tumor effects by reducing prostaglandin (PG) production via the inhibition of cyclooxygenase (COX). However, the gastrointestinal, renal and cardiovascular side effects associated with the pharmacological inhibition of the COX enzymes have focused renewed attention onto other potential targets for NSAIDs. PGH2, a COX metabolite, is converted to each PG species by species-specific PG terminal synthases. Because of their potential for more selective modulation of PG production, PG terminal synthases are now being investigated as a novel target for NSAIDs. In this review, I summarize the current understanding of PG terminal synthases, with a focus on microsomal PGE synthase-1 (mPGES-1) and PGI synthase (PGIS). mPGES-1 and PGIS cooperatively exacerbate inflammatory reactions but have opposing effects on carcinogenesis. mPGES-1 and PGIS are expected to be attractive alternatives to COX as therapeutic targets for several diseases, including inflammatory diseases and cancer.

  • Shuji FUNO
    2017 Volume 93 Issue 9 Pages 724-745
    Published: November 10, 2017
    Released: November 10, 2017
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    Measurement systems are very important in urban design. This article reviews the theories of grid plans, particularly with respect to the spatial formations of ancient capital cities in Asia, and clarifies three Chinese Capital Models. The “Zhōu lǐ” Capital Model (Z) is based on the ancient text “Zhōu lǐ” that makes mention of the ideal city. However, because the description of the physical plan of the city is very brief and includes contradictory elements, conclusions regarding the specifics of the city design are extremely difficult to reach. This article proposes the most appropriate Model (Z) as an architype of the ideal Chinese city. Interestingly, there are no excavated examples of Model (Z). The two existing models, the Chang’an Capital Model (C), which is well known as the model for ancient Japanese capitals like Heiankyo (the present Kyoto) and the Dà Yuán (Dadu) Capital Model (D), the model for the city that is today Beijing, are described as Variants I and II, with a focus on the land division system of bo (street blocks).

Original Article
  • Jun NOJIMA, Shu MEGURO, Naoto OHKAWA, Michiaki FURUKOSHI, Toshihide KA ...
    2017 Volume 93 Issue 9 Pages 746-754
    Published: November 10, 2017
    Released: November 10, 2017
    JOURNALS FREE ACCESS FULL-TEXT HTML

    It is difficult to distinguish the onset of renal function decline from the typical variation in estimated glomerular filtration rate (eGFR) measurements in clinical practice. In this study, we used data analysis incorporating smoothing techniques to identify significant trends despite large amounts of noise. We identified the starting points of meaningful eGFR decline based on eGFR trajectories. This was a retrospective observational study of 2533 type 2 diabetes patients. We calculated 1-year eGFR decline rates from the difference between each eGFR value and that of the previous year. We examined the prediction capacity of 1-year eGFR decline rate for renal prognosis. When we performed receiver operating characteristic analysis, the area under the curve of 1-year eGFR decline rate was 0.963 (95% confidence interval: 0.953–0.973). With a cut-off value of more than 7.5% eGFR decline during a 1-year period, the sensitivity was 98.8% and specificity was 82.3%. The predictive accuracy of 1-year eGFR decline rate for renal prognosis was high.

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