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71.
Arai T Ohno M Inoue H Hayashi S Aoki T Hirokawa H Meguro H Koga Y Oshida K Kainoh M Suyama K Kawai H 《Bioorganic & medicinal chemistry letters》2012,22(15):5118-5122
The discovery that pyrazole-benzyl urea derivatives bearing a 2-molpholinopyrimidine moiety are novel p38α inhibitors is described. A comparative view of the binding modes of SB-203580 and BIRB-796 by structural alignment of two X-ray co-crystal structures was utilized to identify this novel series. Modification of the benzyl group led to compound 2b, a highly potent p38α inhibitor. In in vivo studies, 2b inhibited the production of tumor necrosis factor-alpha in lipopolysaccharide-treated mouse in a dose-dependent manner. Furthermore, the results of a 5-day repeated oral dose toxicity study suggest that 2b has low hepatotoxicity. 相似文献
72.
Farina AP Cecchin D Soares RG Botelho AL Takahashi JM Mazzetto MO Mesquita MF 《Gerodontology》2012,29(2):e155-e160
doi: 10.1111/j.1741‐2358.2010.00435.x Evaluation of Vickers hardness of different types of acrylic denture base resins with and without glass fibre reinforcement Objective: To evaluate the Vickers hardness of different acrylic resins for denture bases with and without the addition of glass fibres. Background: It has been suggested that different polymerisation methods, as well as the addition of glass fibre (FV) might improve the hardness of acrylic. Materials and methods: Five types of acrylic resin were tested: Vipi Wave (VW), microwave polymerisation; Vipi Flash (VF), auto‐polymerisation; Lucitone (LT), QC20 (QC) and Vipi Cril (VC), conventional heat‐polymerisation, all with or without glass fibre reinforcement (GFR) and distributed into 10 groups (n = 12). Specimens were then submitted to Vickers hardness testing with a 25‐g load for 30 s. All data were submitted to anova and Tukey’s HSD test. Results: A significant statistical difference was observed with regard to the polymerisation method and the GFR (p < 0.05). Without the GFR, the acrylic resin VC presented the highest hardness values, and VF and LT presented the lowest. In the presence of GFR, VC resin still presented the highest Vickers hardness values, and VF and QC presented the lowest. Conclusions: The acrylic resin VC and VW presented higher hardness values than VF and QC resins. Moreover, GFR increased the Vickers hardness of resins VW, VC and LT. 相似文献
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75.
The dimeric structure of kinesin superfamily proteins plays an important role in their motile functions and characteristics. In this study, the coiled-coil-forming property of the stalk region (192-346) of Drosophila ncd, a C-terminal kinesin motor protein, was investigated by synthesizing various peptide fragments. The alpha helicity of a set of 46-residue peptides spanning the stalk region appeared too low to form a coiled-coil dimer, probably because of insufficient continuity of the hydrophobic residues at (a and d) core positions in amphipathic heptad repeats. On the other hand, several peptides with leucine residues introduced at core positions or with extensional sequences with high alpha helicity had an advantage in coiled-coil formation. When we analyzed the thermal and urea-induced unfolding of these dimeric peptides, we identified four domains having a relatively high potential to form coiled coils. Among them, three domains on the C-terminal side of the stalk region, i.e., (252-272), (276-330), and (336-346), were in the same heptad frame, although these potential coiled-coil domains were not self-sustaining individually. This is in sharp contrast to the fragment of human kinesin, (332-369), which has an extremely high tendency toward coiled-coil formation. One of the possible triggers for coiled-coil formation of the ncd stalk region may be the interaction between the motor domain and the C-terminal part of the stalk as previously revealed by X-ray crystallography. The residues, S331 and R335, seem to act as a breaking point for alpha-helix continuity. This would make the region (336-346), as the head-stalk joint, more flexible such as seen with a plus-end-directed kinesin, if this region had no interaction with the motor domain. These characteristic differences between ncd and kinesin suggest that the nonlocally sustained coiled coil of ncd is one of the factors important for minus-end-directed motility. 相似文献
76.
Enami Kazuhiko; Ichikawa Mie; Uemura Tomohiro; Kutsuna Natsumaro; Hasezawa Seiichiro; Nakagawa Tsuyoshi; Nakano Akihiko; Sato Masa H. 《Plant & cell physiology》2009,50(2):280-289
Membrane trafficking to the plasma membrane (PM) is a highlyorganized process which enables plant cells to build up theirbodies. SNARE (soluble N-ethylmaleimide-sensitive factor attachmentprotein receptor) genes, which encode the proteins involvedin membrane trafficking, are much more abundant in the Arabidopsisgenome than in that of any other eukaryote. We have previouslyshown that a large number of SNARE molecules in the Arabidopsiscell are localized predominantly on the PM. In the present study,in order to elucidate the physiological function of each PM-localizedSNARE, we analyzed the spatiotemporal expression profiling ofnine SYP1s that are resident in the PM of Arabidopsis, and usedthe information thus acquired to generate transgenic Arabidopsisplants expressing green fluorescent protein-fused Qa-SNAREsunder control of their authentic promoters. Among the nine SYP1s,only SYP132 is expressed ubiquitously in all tissues throughoutplant development. The expression patterns of the other SYP1s,in contrast, are tissue specific, and all different from oneanother. A particularly noteworthy example is SYP123, whichis predominantly expressed in root hair cells during root development,and shows a focal accumulation pattern at the tip region ofroot hairs. These results suggest that SYP132 is involved inconstitutive membrane trafficking to the PM throughout plantdevelopment, while the other SYP1s are involved in membranetrafficking events such as root formation or tip growth of roothair, with some redundancy. 相似文献
77.
Kazumi Shimono Mie Goto Takashi Kikukawa Seiji Miyauchi Mikako Shirouzu Naoki Kamo Shigeyuki Yokoyama 《Protein science : a publication of the Protein Society》2009,18(10):2160-2171
Cell‐free expression has become a highly promising tool for the efficient production of membrane proteins. In this study, we used a dialysis‐based Escherichia coli cell‐free system for the production of a membrane protein actively integrated into liposomes. The membrane protein was the light‐driven proton pump bacteriorhodopsin, consisting of seven transmembrane α‐helices. The cell‐free expression system in the dialysis mode was supplemented with a combination of a detergent and a natural lipid, phosphatidylcholine from egg yolk, in only the reaction mixture. By examining a variety of detergents, we found that the combination of a steroid detergent (digitonin, cholate, or CHAPS) and egg phosphatidylcholine yielded a large amount (0.3–0.7 mg/mL reaction mixture) of the fully functional bacteriorhodopsin. We also analyzed the process of functional expression in our system. The synthesized polypeptide was well protected from aggregation by the detergent‐lipid mixed micelles and/or lipid disks, and was integrated into liposomes upon detergent removal by dialysis. This approach might be useful for the high yield production of functional membrane proteins. 相似文献
78.
Witchweeds (Striga spp.) and broomrapes (Orobanche spp.) are obligate root parasitic plants on economically important field and horticultural crops. The parasites' seeds are induced to germinate by root-derived chemical signals. The radicular end is transformed into a haustorium which attaches, penetrates the host root and establishes connection with the vascular system of the host. Reactions of Lotus japonicus, a model legume for functional genomics, were studied for furthering the understanding of host-parasite interactions. Lotus japonicus was compatible with Orobanche aegyptiaca, but not with Orobanche minor, Striga hermonthica and Striga gesnerioides. Orobanche minor successfully penetrated Lotus japonicus roots, but failed to establish connections with the vascular system. Haustoria in Striga hermonthica attached to the roots, but penetration and subsequent growth of the endophyte in the cortex were restricted. Striga gesnerioides did not parasitize Lotus japonicus. Among seven mutants of Lotus japonicus (castor-5, har1-5, alb1-1, ccamk-3, nup85-3, nfr1-3 and nsp2-1) with altered characteristics in relation to rhizobial nodulation and mycorrhizal colonization, castor-5 and har1-5 were parasitized by Orobanche aegyptiaca with higher frequency than the wild type. In contrast, Orobanche aegyptiaca tubercle development was delayed on the mutants nup85-3, nfr1-3 and nsp2-1. These results suggest that nodulation, mycorrhizal colonization and infection by root parasitic plants in Lotus japonicus may be modulated by similar mechanisms and that Lotus japonicus is a potential model legume for studying plant-plant parasitism. 相似文献
79.
Jessica Mie Ferreira Koyama Takahashi Fernanda Miranda Machado Juliana Maria Costa Nuñez Rafael Leonardo Xediek Consani Marcelo Ferraz Mesquita 《Gerodontology》2009,26(3):232-236
Background: It has been suggested that microwave irradiation and prosthesis immersion in hot water after its polymerization may improve mechanical and viscoelastic properties of acrylic resins. Purpose: This study was proposed to verify the influence of microwave post‐polymerization (PP) treatment over the flexural strength of thermo‐polymerizing acrylic resin specimens (QC‐20) relined or not with two different composition hard chairside auto‐polymerizing reliners [Kooliner (K) and New Truliner (NT)]. Materials and Methods: For this study, 50 specimens of 64 × 10 × 3.3 mm were polymerized and distributed into five groups. G1 (control) specimens without relining and PP; G2 specimens relined with K, without PP; G3 specimens relined with NT, without PP; G4 specimens relined with K, with PP (microwave irradiation with 650 W for 5 min); G5 specimens relined with NT, with PP. Tests were performed on a universal testing machine Instron 4411 with compression speed of 5 mm/min. Results: Specimens of K without PP did not show statistically different results (p < 0.05) when compared with control. However, when submitted to PP these specimens showed a significant increase in flexural strength. Specimens of NT showed the lowest flexural strength of all groups, with or without PP when compared with control and K groups. Conclusion: Microwave PP (650 W for 5 min) proved to be an effective method of improving the flexural strength of K relined prosthesis. However, it did not seem to affect NT specimens. 相似文献
80.
Gun Hyuk Jang In-Sook Park Sun Hee Lee You Mie Lee 《Biochemical and biophysical research communications》2009,382(3):486-14755
Malachite green (MG) is a triphenyl methane dye used in various fields that demonstrates high toxicity to bacteria and mammalian cells. When bud stage zebrafish embryos were treated with MG at 125, 150, and 175 ppb for 14 h, the development of trunk including intersomitic vessels was inhibited in MG-treated flk-1-GFP transgenic embyos. MG clearly induced whole growth retardation. MG induced severe cell death in trunk intersomite region of zebrafish embryos and in human vascular endothelial cells in a dose-dependent manner. MG inhibited heart rates and cardiac looping. MG attenuated whole blood formation and inhibited vascular endothelial growth factor (VEGF)-induced receptor (R)-2 phosphorylation in vascular endothelial cells. In conclusion, MG significantly alters the cardiovascular development causing growth retardation in zebrafish through the blocking VEGFR-2 activation in early cardiovascular development. It suggests that MG may be an environmental toxic agent with the potential to induce embryonic cardiovascular defects in vertebrates. 相似文献