Pleiotropic Effects of Sodium-Glucose Cotransporter-2 Inhibitors: Renoprotective Mechanisms beyond Glycemic Control

Diabetes mellitus is a major cause of chronic kidney disease and end-stage renal disease. However, the management of chronic kidney disease, particularly diabetes, requires vast improvements. Recently, sodium-glucose cotransporter-2 (SGLT2) inhibitors, originally developed for the treatment of diabetes, have been shown to protect against kidney injury via glycemic control, as well as various other mechanisms, including blood pressure and hemodynamic regulation, protection from lipotoxicity, and uric acid control. As such, regulation of these mechanisms is recommended as an effective multidisciplinary approach for the treatment of diabetic patients with kidney disease. Thus, SGLT2 inhibitors are expected to become key drugs for treating diabetic kidney disease. This review summarizes the recent clinical evidence pertaining to SGLT2 inhibitors as well as the mechanisms underlying their renoprotective effects. Hence, the information contained herein will advance the current understanding regarding the pleiotropic effects of SGLT2 inhibitors, while promoting future research in the field.     

Effect of Moving Speed of Charged Metallic Spherical Electrode on Electrostatic Discharge

In this investigation, the nature of the electrostatic discharge (ESD) that occurs when a charged object moves toward a stationary grounded object is experimentally clarified. The spark lengths, discharge currents, and induced voltages in a magnetic probe were measured when a charged metallic spherical electrode connected to a 422 pF capacitor approached a stationary grounded object, which was the current target, for different moving speeds of the charged metallic spherical electrode in a range of 1 mm/s to 100 mm/s. The charge voltages of the capacitor were +6.5 kV and +10 kV. Based on the results, the average gap length shortened with the speed of the spherical electrode. The average peak values of the discharge current and the induced voltage were likely to increase with the speed of the spherical electrode. The average rise times of the discharge current and the induced voltage were likely to drop with the speed of the spherical electrode. The relation between the spark length and the discharge current due to the ESD can be explained qualitatively by using an equation derived from the spark resistance formula proposed by Rompe and Weizel.     

In-fibre LP11–LP21 mode conversion using force-induced long-period fibre gratings with polarization controllers

ABSTRACT

Mode conversion between higher-order modes is attained in a step-index four mode fibre using an in-line polarization controller followed by a force-induced long period fibre grating. By adjusting the field orientation of the LP₁₁ mode to the antisymmetric fibre grating, the LP₁₁ mode is converted to the LP₂₁ mode with a spatially periodic force of 50 N along the fibre length of 50?mm. The mode conversion is evaluated by observing the far-field and near-field patterns of the fibre output and by comparing the transmitted optical power with and without the additional two-mode fibre. The phase-matching grating period is required of the accuracy of roughly ±5?μm and the radiation loss during the mode conversion is as low as 0.01?dB.     

Isolation of antimicrobial agent from the marine algae Cystoseira hakodatensis

Cystoseira hakodatensis is an unutilised brown algae belonging to family Sargassaceae. A crude methanol extract from the algae showed inhibitory effects on the growths of Bacillus cereus and Bacillus licheniformis. To isolate the major antimicrobial agent, a sequential active‐guided isolation procedure was applied: liquid–liquid extraction, column chromatography and bio‐autography. A marked antimicrobial agent (active α) was isolated in hydrophobic fraction and was determined to phenolics without carbohydrates and proteins by phytochemical test. Regarding the antimicrobial potential, the isolated active α showed better inhibitory effects against B. cereus and B. licheniformis at 2 and 4 times of lower concentrations (62.5 and 31.3 μg mL^?1) in comparison with epigallocatechin gallate. These results showed that C. hakodatensis is a potential source of antimicrobial agent capable of preventing the growth of the two bacteria.     

Liposome‐Based in Vitro Evolution of Aminoacyl‐tRNA Synthetase for Enhanced Pyrrolysine Derivative Incorporation

Methanosarcina species pyrrolysyl‐tRNA synthetase (PylRS) attaches Pyl to its cognate amber suppressor tRNA. The introduction of two mutations (Y384F and Y306A) into PylRS was previously shown to generate a mutant, designated LysZ‐RS, that was able to attach N‐benzyloxycarbonyl‐L ‐lysine (LysZ) to its cognate tRNA. Despite the potential of LysZ derivatives, further LysZ‐RS engineering has not been performed; consequently, we aimed to generate LysZ‐RS mutants with improved LysZ incorporation activity through in vitro directed evolution. Using a liposome‐based in vitro compartmentalization (IVC) approach, we screened a randomly mutagenized gene library of LysZ‐RS and obtained a mutant that showed increased LysZ incorporation activity both in vitro and in vivo. The ease and high flexibility of liposome‐based IVC should enable the evolution of not only LysZ‐RS that can attach various LysZ derivatives but also of other enzymes involved in protein translation.     

Forgetting curve of cricket,Gryllus bimaculatus,derived by using serotonin hypothesis

It is thought that the adjustment of intraspecific aggression is an essential factor in the development of a social structure. To understand the natural laws for organizing the social structure, we focus on the fighting behavior of crickets, Gryllus bimaculatus, and investigate the neuronal mechanisms to adjust aggressiveness associated with a neuromodulatory biological amine: serotonin (5-HT).In this paper, we present a working theory of a neurophysiological mechanism based on the past biological studies on the 5-HT hypothesis, and a mathematical model of the mechanism. We analyzed this model and concluded that this neurophysiological mechanism makes the forgetting process slower. Next, we fitted our theoretical forgetting curve to an experimental curve and estimated the parameters of our model. These estimated values were in agreement with common belief in biological science.     

Sustained photobiological hydrogen production in the presence of N2 by nitrogenase mutants of the heterocyst-forming cyanobacterium Anabaena

Heterocyst-forming cells of the cyanobacterium Anabaena sp. strain PCC 7120 ΔHup, lacking an uptake hydrogenase, photobiologically produce H₂ by nitrogenase. Under N₂-rich atmosphere, the nitrogenase activity declines in a rather short time due to the sufficiency of combined nitrogen. From the parental ΔHup strain, site-directed double-crossover variants, dc-Q193S and dc-R284H, were created with amino acid substitutions presumed to be located in the vicinity of the FeMo-cofactor of nitrogenase. Unlike the case for the ΔHup strain, H₂ production activities of the variants were not decreased by the presence of high concentrations of N₂ and they continuously produced H₂ over 21 days with occasional headspace gas replacement. This property of N₂ insensitivity is a potentially useful strategy for reducing the cost of the culture gas in future practical applications of sustainable biofuel production. This Anabaena strain has only the Mo-containing nitrogenase which reduces acetylene to ethylene, but the dc-Q193S variant also produced ethane at low but measurable rates along with greater rates of ethylene production.     

Properties of novel diallyl phthalate resin modified with sulfur‐containing allyl ester compounds

Sulfur‐containing allyl ester, which reacts with diallyl phthalate (DAP) resin to have allyl groups, was synthesized by the reaction of allyl phthalic acid with bisphenol having sulfur atoms. The sulfur‐containing allyl ester compound was blended with DAP resin to improve the adhesive properties to copper. By modification with sulfur‐containing allyl ester compound, the T‐peel adhesive strength and the lap shear adhesive strength to copper was improved. In particular, the adhesive strength was greatly improved when the resin was modified with the allyl ester compound having a disulfide bond (?S?S?) (DADS). It is concluded that this result is due to the improvement of the interfacial adhesive strength because the sulfur atom was found to be located in the surface of the copper by Fourier transform infrared (FTIR) analysis. The glass transition temperature (T_g) and the thermal decomposition temperature (T_d) of the cured DAP resin modified with DADS slightly decreased with increasing concentration of DADS. The lowering of T_g is because the crosslinking density of the DAP resin modified with DADS is smaller than that of DAP resin. Moreover, from thermogravimetric analysis, the lowering of Td of the DAP resin modified with DADS is because DADS is likely to pyrolyze. © 2013 Society of Chemical Industry     

Prediction model of time diversity using Japan rain radar data

The effects of rain attenuation on communication systems will become more pronounced in future satellite communication systems, especially with the planned use of the 21‐GHz band or higher‐frequency bands. Diversity techniques provide a solution to mitigate rain attenuation effects. This study proposes a time diversity technique, one such technique that is likely to demonstrate high effectiveness. To model the system, rainfall rate statistics are necessary, and reliability is improved as the amount of statistical data increases. This paper derives the cumulative distribution of the rainfall rate across Japan over 4 years using rain radar data from the automated meteorological data acquisition system and ground‐based rain radar network and evaluates the rainfall rate at 23 observation points across Japan. We carry out a performance evaluation for all locations within Japan to confirm the efficiency of the time diversity method. Finally, we propose prediction model of the time diversity gain for Japan and other significant parameter which is time correlation of rainfall rate that was found from the time diversity results for further investigation. Copyright © 2016 John Wiley & Sons, Ltd.