The missing link: A single unifying mechanism for diabetic complications

The missing link: A single unifying mechanism for diabetic complications. A causal relationship between chronic hyperglycemia and diabetic microvascular disease, long inferred from various animal and clinical studies, has now been definitely established by data from the Diabetes Control and Complications Trial (DCCT), a multicenter, randomized, prospective, controlled clinical study. A relationship between chronic hyperglycemia and diabetic macrovascular disease in patients with non-insulin-dependent diabetes mellitus (NIDDM) is also supported by the Kumamoto study. How does hyperglycemia induce the functional and morphologic changes that define diabetic complications? Vascular endothelial cells are a major target of hyperglycemic damage, but the mechanisms underlying this damage remain incompletely understood. Three seemingly independent biochemical pathways are involved in the pathogenesis: glucose-induced activation of protein kinase C (PKC) isoforms; increased formation of glucose-derived advanced glycation end products; and increased glucose flux through the aldose reductase pathway. The relevance of each of these three pathways is supported by animal studies in which pathway-specific inhibitors prevent various hyperglycemia-induced abnormalities. Hyperglycemia increases reactive oxygen species (ROS) production inside cultured bovine aortic endothelial cells. In this paper, we show that ROS may activate aldose reductase, induce diacylglycerol, activate PKC, induce advanced glycation end product formation, and activate the pleiotropic transcription factor nuclear factor-kappa B (NF-κ;B). These data demonstrate that a single unifying mechanism of induction, increased production of ROS, serves as a causal link between elevated glucose and each of the three major pathways responsible for diabetic damage

血中成長ホルモン結合蛋白の生理的および病的動態とその意義

取得学位 : 博士（医学）, 学位授与番号 : 医博甲第1005号, 学位授与年月日：平成3年3月25日,学位授与年：199

Phylogenetic position of a whale-fall lancelet (Cephalochordata) inferred from whole mitochondrial genome sequences

<p>Abstract</p> <p>Background</p> <p>The lancelet <it>Asymmetron inferum </it>(subphylum Cephalochordata) was recently discovered on the ocean floor off the southwest coast of Japan at a depth of 229 m, in an anaerobic and sulfide-rich environment caused by decomposing bodies of the sperm whale <it>Physeter macrocephalus</it>. This deep sulfide-rich habitat of <it>A. inferum </it>is unique among the lancelets. The distinguishing adaptation of this species to such an extraordinary habitat can be considered in a phylogenetic framework. As the first step of reconstruction of the evolutionary processes in this species, we investigated its phylogenetic position based on 11 whole mitochondrial genome sequences including the newly determined ones of the whale-fall lancelet <it>A. inferum </it>and two coral-reef congeners.</p> <p>Results</p> <p>Our phylogenetic analyses showed that extant lancelets are clustered into two major clades, the <it>Asymmetron </it>clade and the <it>Epigonichthys </it>+ <it>Branchiostoma </it>clade. <it>A. inferum </it>was in the former and placed in the sister group to <it>A. lucayanum </it>complex. The divergence time between <it>A. inferum </it>and <it>A. lucayanum </it>complex was estimated to be 115 Mya using the penalized likelihood (PL) method or 97 Mya using the nonparametric rate smoothing (NPRS) method (the middle Cretaceous). These are far older than the first appearance of large whales (the middle Eocene, 40 Mya). We also discovered that <it>A. inferum </it>mitogenome (mitochondrial genome) has been subjected to large-scale gene rearrangements, one feature of rearrangements being unique among the lancelets and two features shared with <it>A. lucayanum </it>complex.</p> <p>Conclusion</p> <p>Our study supports the monophyly of genus <it>Asymmetron </it>assumed on the basis of the morphological characters. Furthermore, the features of the <it>A. inferum </it>mitogenome expand our knowledge of variation within cephalochordate mitogenomes, adding a new case of transposition and inversion of the <it>trnQ </it>gene. Our divergence time estimation suggests that <it>A. inferum </it>remained a member of the Mesozoic and the early Cenozoic large vertebrate-fall communities before shifting to become a whale-fall specialist.</p

Optical and radiographical characterization of silica aerogel for Cherenkov radiator

We present optical and X-ray radiographical characterization of silica aerogels with refractive index from 1.05 to 1.07 for a Cherenkov radiator. A novel pin-drying method enables us to produce highly transparent hydrophobic aerogels with high refractive index by shrinking wet-gels. In order to investigate the uniformity in the density (i.e., refractive index) of an individual aerogel monolith, we use the laser Fraunhofer method, an X-ray absorption technique, and Cherenkov imaging by a ring imaging Cherenkov detector in a beam test. We observed an increase in density at the edge of the aerogel tiles, produced by pin-drying.Comment: To be published in IEEE Trans. Nucl. Sci., 7 pages, 9 figures, 1 tabl

Synthesis of solvent-free conductive and flexible cellulose-carbon nanohorn sheets and their application as a water vapor sensor

Carbon nanohorns (CNHs) are mixed with cellulose to make freestanding thin-film conductive sheets. CNHs, at different ratios (5, 10, 25, 50 wt%), form composites with cellulose (hydroxyethylcellulose). Freestanding cellulose-carbon nanohorn (CCN) sheets were fabricated using a 100 mu m-thick metal bar coater. Surfactants or any other chemical treatments to tailor the surface properties of CNHs were avoided to obtain composite sheets from pristine CNHs and cellulose. Utilizing the hygroscopic property of hydroxyethylcellulose and the electrical conductivity of CNHs paved a path to perform this experiment. The synthesis technique is simple, and the fabrication and drying of the sheets were effortless. As the loading concentration of CNH increased, the resistance, flexibility, and strength of the CCN composite sheets decreased. The maximum loading concentration possible to obtain a freestanding CCN sheet is 50 wt%. The resistance of the maximum loading concentration of CNH was 53 k omega. The response of the CCN sheets to water vapor was 4 s and recover time was 13 s, and it is feasible to obtain a response for different concentrations of water vapor. High-resolution transmission electron microscopy, scanning electron microscopy, Fourier transform infrared spectroscopy, Raman spectroscopy, resistance measurement, tensile strength measurement, and thermogravimetric analysis were used to investigate the mechanical, morphological, electrical, and chemical properties of the CCN sheets

Am80, a retinoic acid receptor agonist, activates the cardiomyocyte cell cycle and enhances engraftment in the heart

ヒトiPS細胞由来心筋細胞の生着能改善に向けた新しい方法. 京都大学プレスリリース. 2023-07-14.Am80, a retinoic acid receptor agonist, activates cell cycle in induced cardiomyocytes and enhances heart tissue engraftment. 京都大学プレスリリース. 2023-07-14.Human induced pluripotent stem cell-derived (hiPSC) cardiomyocytes are a promising source for regenerative therapy. To realize this therapy, however, their engraftment potential after their injection into the host heart should be improved. Here, we established an efficient method to analyze the cell cycle activity of hiPSC cardiomyocytes using a fluorescence ubiquitination-based cell cycle indicator (FUCCI) system. In vitro high-throughput screening using FUCCI identified a retinoic acid receptor (RAR) agonist, Am80, as an effective cell cycle activator in hiPSC cardiomyocytes. The transplantation of hiPSC cardiomyocytes treated with Am80 before the injection significantly enhanced the engraftment in damaged mouse heart for 6 months. Finally, we revealed that the activation of endogenous Wnt pathways through both RARA and RARB underlies the Am80-mediated cell cycle activation. Collectively, this study highlights an efficient method to activate cell cycle in hiPSC cardiomyocytes by Am80 as a means to increase the graft size after cell transplantation into a damaged heart

Comparison of muscle strength between Japanese men with and without metabolic syndrome

We compared muscle strength between Japanese men with and without metabolic syndrome. We used data for 323 Japanese men with metabolic syndrome and 893 Japanese men without the syndrome. Metabolic syndrome was defined by a new criterion in Japan, and the parameters for muscle strength, i.e. grip strength, leg strength were measured. Leg strength was found to be significantly higher in subjects with metabolic syndrome than in those without, while muscle strength per body weight was significantly lower in subjects with the syndrome. Lower muscle strength per body weight may be one of the characteristic features in subjects with metabolic syndrome.</p