Study on long-life technology for external building walls through the two new technical methods

広島大学(Hiroshima University)博士(工学)Doctor of Engineeringdoctora

Glycocalyx Degradation in Retinal and Choroidal Capillary Endothelium in Rats with Diabetes and Hypertension

Endothelial glycocalyx (GCX) has been reported as a protective factor for vascular endothelial cells (VEC) in diabetes and hypertension. However, the involvement of GCX impairment in ocular vasculopathy remains unclear. We evaluated the changes in the GCX thicknesses of the retinal and choroidal capillaries in rats with diabetes and hypertension by cationic colloidal iron staining using a transmission electron microscope. In the control group, the mean (standard error of the mean) thicknesses of retinal and choroidal GCX were 60.2 (1.5) nm and 84.3 (3.1) nm, respectively. The diabetic rats showed a significant decrease of GCX thickness in the retina, but not in the choroid, compared to controls (28.3 (0.3) nm, p＜0.01 and 77.8 (1.4) nm, respectively). In the hypertensive rats, both retinal and choroidal GCX were significantly decreased compared to the control values (10.9 (0.4) nm and 13.2 (1.0) nm, respectively, both p＜0.01). Moreover, we could visualize the adhesion of leukocytes and platelets on the luminal surface of VEC, at the site where the GCX was markedly degraded. These findings suggest that the GCX prevents adhesion of leukocytes and platelets to the VEC surface, and this impairment may lead to ocular vasculopathy in diabetes and hypertension

Elimination of fukutin reveals cellular and molecular pathomechanisms in muscular dystrophy-associated heart failure

Heart failure is the major cause of death for muscular dystrophy patients, however, the molecular pathomechanism remains unknown. Here, we show the detailed molecular pathogenesis of muscular dystrophy-associated cardiomyopathy in mice lacking the fukutin gene (Fktn), the causative gene for Fukuyama muscular dystrophy. Although cardiac Fktn elimination markedly reduced alpha-dystroglycan glycosylation and dystrophin-glycoprotein complex proteins in sarcolemma at all developmental stages, cardiac dysfunction was observed only in later adulthood, suggesting that membrane fragility is not the sole etiology of cardiac dysfunction. During young adulthood, Fktn-deficient mice were vulnerable to pathological hypertrophic stress with downregulation of Akt and the MEF2-histone deacetylase axis. Acute Fktn elimination caused severe cardiac dysfunction and accelerated mortality with myocyte contractile dysfunction and disordered Golgi-microtubule networks, which were ameliorated with colchicine treatment. These data reveal fukutin is crucial for maintaining myocyte physiology to prevent heart failure, and thus, the results may lead to strategies for therapeutic intervention

Turtle spongious ventricles exhibit more compliant diastolic property and possess larger elastic regions of connectin in comparison to rat compact left ventricles

There is growing evidence that ventricular diastolic dysfunction is a major pathological factor in heart failure. Although many basic and clinical studies have been reported, there is little information available about the comparative and evolutionary aspects of the diastolic properties of vertebrate ventricles. Cardiac tissues in extant vertebrates are roughly divided into two types; compact myocardium in mammals and aves, and spongious myocardium in amphibians and some of reptilians. Here we compared the mechanical properties of both whole ventricles and the biochemical properties of isolated cardiomyocytes (including intracelluar Ca2+ ([Ca2+]i) handling, and the lengths of elastic regions of connectin, a protein that determines elasticity of cardiomyocytes) between spongious ventricles of turtles (Trachemys scripta elegans) and compact ventricles of Wister rats. Ventricular diastolic function is composed of active relaxation and passive compliance. We investigated ventricular compliance by analyzing normalized end-diastolic pressure-volume relationship (EDPVR) of diastolic-arrested ventricles to compare different-sized hearts and ventricular relaxation by determining logistic time constants of pressure decay. We measured [Ca2+]i handling using isolated cardiomyocytes. Stiffness constants obtained from exponential curve fitting were significantly larger in rat left ventricles (LVs) compared with turtle ventricles (99.0 ± 7.3 and 2.07 ± 0.62, respectively) showing that rat LVs were much stiffer than turtle ventricles. Normalization of EDPVRs revealed that the turtle ventricle and rat LV exhibit species-specific characteristics in ventricular compliance. At the cellular level, the initial normalized stiffness of rat cardiomyocytes (8.03 ± 1.33 kPa) was 2.8 times higher than in those of the turtle (2.82 ± 0.38 kPa), showing that turtle cardiomyocytes were much more compliant than those of rats. With respect to relaxation, the time constant of isovolumic relaxation in the rat LV pressuretime curve was significantly smaller than that in turtle ventricles (10.7 ± 0.96 and 67.4 ± 3.55 ms, respectively), resulting in early-phase-dominant ventricular filling patterns in rats. The time to peak [Ca2+]i and the decay time after peak [Ca2+]i in turtle cardiomyocytes were significantly longer than in rat. The numbers of amino acids of the PEVK domain of connectin, which is enriched in proline, glutamic acid, valine and lysine and encodes a random coil shown to be an important region in the passive elasticity of connectin were 821 and 204 in turtle and rat ventricles, respectively. These results suggest that vertebrate hearts have been becoming less compliant at the ventricle, cardiomyocyte, and molecular levels during the course of evolution. One possible physiological meaning of restricted compliance in rat ventricles could be related to a well-developed coronary circulation, because the less compliant mechanical properties of the ventricle are largely advantageous to preserve diastolic-dominant coronary arterial flow by preventing excessive ventricular expansion. Future research aimed at understanding the regulatory mechanisms of cardiac connectin among vertebrates may contribute to the investigation of the therapeutic potential of diastolic heart failure

TRPV2 is critical for the maintenance of cardiac structure and function in mice

The heart has a dynamic compensatory mechanism for haemodynamic stress. However, the molecular details of how mechanical forces are transduced in the heart are unclear. Here we show that the transient receptor potential, vanilloid family type 2 (TRPV2) cation channel is critical for the maintenance of cardiac structure and function. Within 4 days of eliminating TRPV2 from hearts of the adult mice, cardiac function declines severely, with disorganization of the intercalated discs that support mechanical coupling with neighbouring myocytes and myocardial conduction defects. After 9 days, cell shortening and Ca2+ handling by single myocytes are impaired in TRPV2-deficient hearts. TRPV2-deficient neonatal cardiomyocytes form no intercalated discs and show no extracellular Ca2+-dependent intracellular Ca2+ increase and insulin-like growth factor (IGF-1) secretion in response to stretch stimulation. We further demonstrate that IGF-1 receptor/PI3K/Akt pathway signalling is significantly downregulated in TRPV2-deficient hearts, and that IGF-1 administration partially prevents chamber dilation and impairment in cardiac pump function in these hearts. Our results improve our understanding of the molecular processes underlying the maintenance of cardiac structure and function

Left ventricular mechanics and myocardial calcium dynamics in short-term and long-term hyperthyroid mice

The thyroid hormone is involved in cardiac adaptation to physiological and pathological stimuli. Although short-term hyperthyroidism enhances cardiac performance, longstanding hyperthyroidism can cause impairment of the contractility by pathological Ca2+ handling. Because the thyroid hormone affects cardiovascular hemodynamics by decreasing systemic arterial resistance and increasing circulating blood volume, it is important to accurately analyze left ventricular (LV) mechanics by using an index that is independent of ventricular loading conditions. Therefore, we adopted the end-systolic elastance (Ees), which is obtained by the linear regression of the end-systolic pressure-volume relationships. This reflects sensitive changes in the contractile state in a manner independent of both preload and afterload, providing an index of LV contractility. To better understand the hypertrophy caused by hyperthyroidism, we normalized the Ees according to LV weight for different sized heart. Hyperthyroidism was induced by a daily intraperitoneal injection of triiodothyronine (T3) at a dose of 2,000mg/kg body weight. Mice were divided into three groups: the synchronous control group, the T3 administration for one-week group (T3-short), and the T3 administration for eight-week group (T3-long). We investigated global LV mechanics, the expression of Na+/Ca2+ exchanger (NCX), the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA), and the Ca2+ handling of isolated cardiomyocytes in each group. Ees values in the control and T3-short were similar, and those in T3-long were significantly smaller than the control (256±60, 249±70 and 154±57mmHg・ml-1・gLV-1, respectively). The values of arterial elastance in both T3-short and T3-long, which represent afterload, were significantly smaller than the control. NCX expression was decreased in T3-short and declined in a time-dependent manner in T3-long. On the other hand, SERCA expression was rapidly elevated in T3-short and remained high in T3-long. These changes may be beneficial for cardiomyocytes in terms of O2 consumption for excitation-contraction coupling. In isolated cardiomyocyte experiments, cell shortening of T3-long mice was significantly lower than that of the control mice, but the average peak amplitude of Ca^ transients in T3-long was 79% and not significantly different. In conclusion, we evaluated LV contractility by using an Ees index in hyperthyroid mice. Although T3 administration shifted the Ca^ route in excitation-contraction coupling to the O_2-saving energetics, LV contractility was diminished with long-term T3 administration, showed constancy in peak amplitude of the Ca^ transients, and a decrease in NCX activity

Estimating rice yield related traits and quantitative trait loci analysis under different nitrogen treatments using a simple tower-based field phenotyping system with modified single-lens reflex cameras

CIAT- Outstanding Research Publication Award (ORPA) - 2017Application of field based high-throughput phenotyping (FB-HTP) methods for monitoring plant performance in real field conditions has a high potential to accelerate the breeding process. In this paper, we discuss the use of a simple tower based remote sensing platform using modified single-lens reflex cameras for phenotyping yield traits in rice under different nitrogen (N) treatments over three years. This tower based phenotyping platform has the advantages of simplicity, ease and stability in terms of introduction, maintenance and continual operation under field conditions. Out of six phenological stages of rice analyzed, the flowering stage was the most useful in the estimation of yield performance under field conditions. We found a high correlation between several vegetation indices (simple ratio (SR), normalized difference vegetation index (NDVI), transformed vegetation index (TVI), corrected transformed vegetation index (CTVI), soil-adjusted vegetation index (SAVI) and modified soil-adjusted vegetation index (MSAVI)) and multiple yield traits (panicle number, grain weight and shoot biomass) across a three trials. Among all of the indices studied, SR exhibited the best performance in regards to the estimation of grain weight (R2 = 0.80). Under our tower-based field phenotyping system (TBFPS), we identified quantitative trait loci (QTL) for yield related traits using a mapping population of chromosome segment substitution lines (CSSLs) and a single nucleotide polymorphism data set. Our findings suggest the TBFPS can be useful for the estimation of yield performance during early crop development. This can be a major opportunity for rice breeders whom desire high throughput phenotypic selection for yield performance traits