Development of a Novel Antibacterial Medicine that Targets a Characteristic Lipid of the Cell Membranes of <em>Helicobacter pylori</em>

Helicobacter pylori is one of the most prevalent causes of gastritis. This pathogen colonizes for many years human stomach and asymptomatically leads the persons to chronic gastritis. The eradication of H. pylori from human stomach is, therefore, important in order to prevent the digestive diseases including peptic ulcers and gastric cancer that develop via chronic atrophic gastritis. Wide-spectrum antibiotics such as amoxicillin and metronidazole are used for the treatment for H. pylori infectious diseases. However, the H. pylori strains resistant to these antibiotics are increasing year by year around the world. On this basis, we need urgently to develop the antibacterial medicines that act on H. pylori with a novel mechanism. Recent studies by our group have demonstrated that H. pylori shows susceptibility to the bactericidal action of indene compounds derived from decomposition of vitamin D. The bactericidal action of indene compounds is selective not against commonplace bacteria but against H. pylori. The indene compounds turned out to target the H. pylori’s phosphatidylethanolamine that retains a myristic acid as the saturated fatty acid side chain. These findings will contribute to the development of new antibacterial medicines specialized to the treatment for H. pylori infectious diseases

A mechanism of ion temperature peaking by impurity pellet injection in a heliotron plasma

Experiments on the Large Helical Device with the injection of carbon pellets into discharges of low density have demonstrated a significant reduction of the ion heat conduction in the plasma core and an increase in the central ion temperature by a factor of up to 2. These results are interpreted in the framework of a transport model elaborated on the basis of those applied previously to explain the improvement in confinement by impurity seeding into the tokamak devices TEXTOR and JET. The calculations performed reproduce well the strong peaking of the ion temperature profile with increasing carbon density nZ and the consequent drop in the confinement as nZ exceeds a certain critical level. The importance of different elements in the model, such as braking of the main ion rotation by friction with impurity ones and the shape of the density profiles, are investigated. A qualitative assessment of the applicability under fusion reactor conditions, e.g. of much higher plasma density and heating power, is performed

Regulation of cargo-selective endocytosis by dynamin 2 GTPase-activating protein girdin.

In clathrin-mediated endocytosis (CME), specificity and selectivity for cargoes are thought to be tightly regulated by cargo-specific adaptors for distinct cellular functions. Here, we show that the actin-binding protein girdin is a regulator of cargo-selective CME. Girdin interacts with dynamin 2, a GTPase that excises endocytic vesicles from the plasma membrane, and functions as its GTPase-activating protein. Interestingly, girdin depletion leads to the defect in clathrin-coated pit formation in the center of cells. Also, we find that girdin differentially interacts with some cargoes, which competitively prevents girdin from interacting with dynamin 2 and confers the cargo selectivity for CME. Therefore, girdin regulates transferrin and E-cadherin endocytosis in the center of cells and their subsequent polarized intracellular localization, but has no effect on integrin and epidermal growth factor receptor endocytosis that occurs at the cell periphery. Our results reveal that girdin regulates selective CME via a mechanism involving dynamin 2, but not by operating as a cargo-specific adaptor

シセツ サイバイ ニ オケル トマト カジツ レッカ ハッセイ ヨウイン ノ カイセキ

収穫直前に発生するトマト果実の裂果について発生要因を探るため,埼玉県滑川町の農業生産法人において3年間の果実収量,裂果率,および当該地域の気象条件を踏まえ,温室内における気象条件の推移と裂果発生との関係について調査検討した。トマト果実の裂果は,例年4月から6月に発生頻度が高くなるが,温室内の気温および湿度が大きく変動する時期であり,1日における,気温および湿度も日ごとに大きく変動する。これら日中の気温および湿度から飽差を算出し裂果発生との関係について検討した結果,日毎の飽差の差と裂果発生との間には正の相関がみられた。このことから,裂果の発生には,飽差の変動が関与している可能性が示唆された。Fruit cracking occurring just before harvesting is one of the most delicate problems in tomato greenhouse cultivation. In this study we investigated the relationship between fruit cracking and meteorological factors in the greenhouse. As a result, it was suggested that the sharp fluctuations of temperature and humidity of the greenhouse were closely associated with fruit cracking. In particular the vapor pressure of deficit (VPD) in the greenhouse calculated from value of temperature and humidity was indicated to have a significant correlation with fruit cracking. Therefore the control of VPD can be a possible countermeasure to suppress Tomato fruit cracking

Carbon impurities behavior and its impact on ion thermal confinement in high-ion-temperature deuterium discharges on the Large Helical Device

The behavior of carbon impurities in deuterium plasmas and its impact on thermal confinement were investigated in comparison with hydrogen plasmas in the Large Helical Device (LHD). Deuterium plasma experiments have been started in the LHD and high-ion-temperature plasmas with central ion temperature (T i) of 10 keV were successfully obtained. The thermal confinement improvement could be sustained for a longer time compared with hydrogen plasmas. An isotope effect was observed in the time evolution of the carbon density profiles. A transiently peaked profile was observed in the deuterium plasmas due to the smaller carbon convection velocity and diffusivity in the deuterium plasmas compared with the hydrogen plasmas. The peaked carbon density profile was strongly correlated to the ion thermal confinement improvement. The peaking of the carbon density profile will be one of the clues to clarify the unexplained mechanisms for the formations of ion internal transport barrier and impurity hole on LHD. These results could also lead to a better understanding of the isotope effect in the thermal confinement in torus plasma

Effects of single therapeutic doses of promethazine, fexofenadine and olopatadine on psychomotor function and histamine-induced wheal- and flare-responses: a randomized double-blind, placebo-controlled study in healthy volunteers

Since most first-generation antihistamines have undesirable sedative effects on the central nervous systems (CNS), newer (second-generation) antihistamines have been developed to improve patients’ quality of life. However, there are few reports that directly compare the antihistaminic efficacy and impairment of psychomotor functions. We designed a double-blind, placebo controlled, crossover study to concurrently compare the clinical effectiveness of promethazine, a first-generation antihistamine, and fexofenadine and olopatadine, second-generation antihistamines, by measuring their potency as peripheral inhibitors of histamine-induced wheal and flare. Further, we investigated their sedative effects on the CNS using a battery of psychomotor tests. When single therapeutic doses of fexofenadine (60 mg), olopatadine (5 mg) and promethazine (25 mg) were given in a double-blind manner to 24 healthy volunteers, all antihistamines produced a significant reduction in the wheal and flare responses induced by histamine. In the comparison among antihistamines, olopatadine showed a rapid inhibitory effect compared with fexofenadine and promethazine, and had a potent effect compared with promethazine. In a battery of psychomotor assessments using critical flicker fusion, choice reaction time, compensatory tracking, rapid visual information processing and a line analogue rating scale as a subjective assessment of sedation, promethazine significantly impaired psychomotor function. Fexofenadine and olopatadine had no significant effect in any of the psychomotor tests. Promethazine, fexofenadine and olopatadine did not affect behavioral activity, as measured by wrist actigraphy. These results suggest that olopatadine at a therapeutic dose has greater antihistaminergic activity than promethazine, and olopatadine and fexofenadine did not cause cognitive or psychomotor impairment

Transport characteristics of deuterium and hydrogen plasmas with ion internal transport barrier in the Large Helical Device

A remarkable extension of the high-ion-temperature (high-Ti) regime was obtained in deuterium plasma experiments in the Large Helical Device. In order to clarify transport characteristics in the ion internal transport barrier (ITB) formation with an isotope effect, a dataset of pure deuterium (nD/ne  >  0.8) and pure hydrogen (nH/ne  >  0.8) plasmas in the high-Ti regime were analyzed, and two mechanisms of transport improvement were characterized. A significant reduction of ion heat transport in the core of both deuterium and hydrogen plasmas was observed, indicating ion ITB formation. The dependence of the ion heat diffusivity on temperature ratio (Te/Ti) and normalized Ti-gradient (R/LTi  =  −(R/Ti)(dTi/dr)) was investigated in the core region, in which gyrokinetic simulations with the GKV code predict the destabilization of ion temperature gradient (ITG) modes. The Te/Ti dependence shows ITG-like property, while a significant deviation from the ITG-like property is found in the R/ dependence, indicating suppression of the ITG mode in the large R/ regime and resultant ion ITB formation. In the comparison between deuterium plasma and hydrogen plasma, the lower transport in the deuterium plasma is observed in both ion and electron heat diffusivities, indicating a significant isotope effect. It was found with the nonlinear turbulent transport simulation with GKV that the zonal flow enhancement contributes to the ITG suppression in the deuterium plasma