Studies on Regioselective Binding Mode of Steroid Molecules in Homology Modeled Cytochrome P450-2C11

In this study, we investigated the regioselective binding mode of steroid molecules and structure requirements for steroid molecules for 16[alpha]-hydroxylation by Cytochrome P450-2C11. Docking study by using the homology Cytochrome P450-2C11 indicated that 16[alpha]-hydroxylation is favored with steroidal molecules possessing the following components, 1) a bent A-B ring configuration (5[beta]-reduced), 2) C-3[alpha]-hydroxyl group, 3) C-17[beta]-acetyl group, and 4) methyl group at both the C-18 and C-19. These respective steroid components requirements such as A-B ring configuration and functional groups at C-3 and C-17 were defined as the inhibitory contribution factor. Overall results by rat CYP2C11 revealed that steroidal structure requirements resulted in causing an effective inhibition of [^3^H]progesterone 16[alpha]-hydroxylation by the adult male rat liver microsome. As far as docking of homology modeled CYP2C11 against investigated steroids is concerned, they are docked at the active site superimposed with flurbiprofen. It was also found that the distance between heme iron and C16[alpha]-H was between 4 to 6 Å and that the related angle was in the range of 180±45°

Recent Trends and Innovations in Modelling City Logistics

AbstractThere are many challenges associated with moving goods within cities as urban areas become larger and elderly residents require more healthcare in their homes. Air quality is also impacted by urban freight vehicles. This paper presents a review of recent trends and innovations in modelling city logistics. New techniques for modelling city logistics developed in the areas of emissions, healthcare and mega-cities are outlined. This paper describes the formulation, solution methodologies and applications of these models

Effect of some Kampo medicines, including Tokaku-joki-to (Tao-He-Cheng-Qi-Tang), on IgE-mediated triphasic skin reaction in passively sensitized mice

Previous studies have reported that the mice passively sensitized with anti-DNP IgE antibody exhibited IgE-mediated biphasic cutaneous reaction with an immediate phase response (IPR) at 1 h and a late phase response (LPR) at 24 h after the challenge of DNFB (dinitrofluorobenzene) . We recently found that the third phase inflammatory response with intense and persisting infiltration of eosinophils, named very late phase response (vLPR) , was induced following IPR and LPR in response to DNFB in passively sensitized mice, and that the peak response of vLPR was on the 8^ day after the challenge. The inhibitory effect of Kampo medicines on the triphasic cutaneous inflammatory reaction was divided into several groups in terms of their inhibition rate of ear swelling. Among the formulations, Tokaku-joki-to (Tao-He-Cheng-Qi-Tang) was effective at inhibiting IPR, LPR and vLPR ( +/+/+ group) and scratching behavior in IPR. The Inhibitory effect of Tokaku-joki-to on triphasic cutaneous reaction primarily depends on its composed crude drugs, Glycyrrhizae Radix and Cinnamomi Cortex. These findings indicate that Tokaku-joki-to formulation is usefull for the inhibition of cutaneous inflammatory diseases. 抗DNP IgE抗体で受動感作したマウスの耳介にDNFB(ジニトロフルオロベンゼン)を塗布することにより,1時問およぴ24時間目をピークとする即時相反応(IPR)およぴ遅発相反応(LPR)からなるIgE介在二相性皮膚反応を示すことがすでに知られている。我々は最近,この受動感作マウスにおいてDNFBによる反応惹起後にIPR,LPRに続く,三相目の強い炎症性反応を見出し,超遅発相反応(vLPR)と名付けた。これは抗原塗布から8日目をピークとする,著明かつ持続的な好酸球の浸潤を伴う腫脹反応である。種々の漢方方剤を用いて,この三相性皮膚反応に対する抑制効果を検討した結果,各相の耳介腫脹の抑制率に基づき,いくつかのグループに分類された。検討した方剤中,桃核承気湯はIPR,LPR,vLPRの三相反応に対して抑制を示し(+/+/+群),さらにIPRで観察される耳介の掻き行動(痒みの指標と考えられる)を抑制した。桃核承気湯の三相性皮膚反応に対する抑制効果の発現は,主として構成生薬である甘草およぴ桂皮に基づくことが示唆された。これらの知見から,漢方方剤:桃核承気湯が炎症性皮膚疾患に有効であることが示された

Assessment of energy expenditure using doubly labeled water, physical activity by accelerometer and reported dietary intake in Japanese men with type 2 diabetes: A preliminary study

The aim of the present study was to determine the total energy expenditure, physical activity and dietary intake of men with type 2 diabetes mellitus and control participants without type 2 diabetes mellitus who were matched for age and body mass index. The participants in the present study were 12 well‐controlled type 2 diabetes mellitus patients and 10 controls, aged 40–75 years, with a body mass index <30 kg/m2. Total energy expenditure under free‐living conditions was assessed using the doubly labeled water method, and physical activity was measured using a triaxial accelerometer. Dietary intake was assessed using a self‐recorded food intake diary during the measurement period. Participants were instructed to record their dietary intake over 3 days, including 2 weekdays. Total energy expenditure was not significantly different between the groups (P = 0.153), nor were energy (P = 0.969) or macronutrient intakes. In conclusion, when age and body mass index are matched, total energy expenditure and self‐reported energy intake are not significantly different between type 2 diabetes mellitus patients and healthy controls

Study on Static and Dynamic Instability of Super Long-Span Cable-Stayed Bridges

ABSTRACT: In this paper, the static and dynamic wind-induced instability analyses of super long-span cable-stayed bridges with main span length of 1200～1800m are presented. Firstly, the static behaviors of bridges against displacement-dependent wind load are investigated by three-dimension geometrical nonlinear analysis. Secondly, the free vibration and flutter analyses are carried out and the comparison of dynamic structural properties between cable-stayed and suspension bridges are discussed. Finally, the possibility and limitations of long-span cablestayed bridges based on static and dynamic instability analyses are discussed. The analytical results show that static instability controls the dimension of the girder and the safety against both static and dynamic instabilities can be ensured even with main span length of 1800m

S100C/A11 is a key mediator of Ca2+-induced growth inhibition of human epidermal keratinocytes

An increase in extracellular Ca2+ induces growth arrest and differentiation of human keratinocytes in culture. We examined possible involvement of S100C/A11 in this growth regulation. On exposure of the cells to high Ca2+, S100C/A11 was specifically phosphorylated at 10Thr and 94Ser. Phosphorylation facilitated the binding of S100C/A11 to nucleolin, resulting in nuclear translocation of S100C/A11. In nuclei, S100C/A11 liberated Sp1/3 from nucleolin. The resulting free Sp1/3 transcriptionally activated p21CIP1/WAF1, a representative negative regulator of cell growth. Introduction of anti-S100C/A11 antibody into the cells largely abolished the growth inhibition induced by Ca2+ and the induction of p21CIP1/WAF1. In the human epidermis, S100C/A11 was detected in nuclei of differentiating cells in the suprabasal layers, but not in nuclei of proliferating cells in the basal layer. These results indicate that S100C/A11 is a key mediator of the Ca2+-induced growth inhibition of human keratinocytes in culture, and that it may be possibly involved in the growth regulation in vivo as well

Discovery of a Giant Lyα Emitter Near the Reionization Epoch

‘In these times, during the rise in the popularity of institutional repositories, the Society does not forbid authors from depositing their work in such repositories. However, the AAS regards the deposit of scholarly work in such repositories to be a decision of the individual scholar, as long as the individual's actions respect the diligence of the journals and their reviewers.’ Original article can be found at : http://iopscience.iop.org/ Copyright American Astronomical SocietyWe report the discovery of a giant Lyα emitter (LAE) with a Spitzer/Infrared Array Camera (IRAC) counterpart near the reionization epoch at z = 6.595. The giant LAE is found from the extensive 1 deg2 Subaru narrowband survey for z = 6.6 LAEs in the Subaru/XMM-Newton Deep Survey (SXDS) field, and subsequently identified by deep spectroscopy of Keck/DEIMOS and Magellan/IMACS. Among our 207 LAE candidates, this LAE is not only the brightest narrowband object with L(Lyα) = 3.9 ± 0.2 × 1043 erg s–1 in our survey volume of 106 Mpc3, but also a spatially extended Lyα nebula with the largest isophotal area whose major axis is at least 3''. This object is more likely to be a large Lyα nebula with a size of 17 kpc than to be a strongly lensed galaxy by a foreground object. Our Keck spectrum with medium-high spectral and spatial resolutions suggests that the velocity width is v FWHM = 251 ± 21 km s–1, and that the line-center velocity changes by 60 km s–1 in a 10 kpc range. The stellar mass and star formation rate are estimated to be 0.9-5.0 × 1010 M and >34 M yr–1, respectively, from the combination of deep optical to infrared images of Subaru, UKIDSS-Ultra Deep Survey, and Spitzer/IRAC. Although the nature of this object is not yet clearly understood, this could be an important object for studying cooling clouds accreting onto a massive halo, or forming-massive galaxies with significant outflows contributing to cosmic reionization and metal enrichment of intergalactic medium.Peer reviewe