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951.
Yamamoto K Choi M Abe D Shimizu M Yamada S 《The Journal of steroid biochemistry and molecular biology》2007,103(3-5):282-285
We achieved exhaustive alanine scanning mutational analysis of the amino acid residues lining the ligand binding pocket of the Vitamin D receptor to investigate the mechanism of the ligand recognition by the receptor. This is the first exhaustive analysis in the nuclear receptor superfamily. Our results demonstrated the role and importance of all the residues lining the ligand binding pocket. In addition, this analysis was found to indicate ligand-specific ligand-protein interactions, which have key importance in determining the transactivation potency of the individual ligands. Thus, the analysis using 1beta-methyl-1alpha,25-dihydroxyvitamin D(3) revealed the specific van der Waals interactions of 1beta-methyl group with the receptor. 相似文献
952.
953.
954.
Characterization of the centromere and peri-centromere retrotransposons in Brassica rapa and their distribution in related Brassica species 总被引:2,自引:0,他引:2
Lim KB Yang TJ Hwang YJ Kim JS Park JY Kwon SJ Kim J Choi BS Lim MH Jin M Kim HI de Jong H Bancroft I Lim Y Park BS 《The Plant journal : for cell and molecular biology》2007,49(2):173-183
We report the identification and characterization of the major repeats in the centromeric and peri-centromeric heterochromatin of Brassica rapa. The analysis involved the characterization of 88 629 bacterial artificial chromosomes (BAC) end sequences and the complete sequences of two BAC clones. We identified centromere-specific retrotransposons of Brassica (CRB) and various peri-centromere-specific retrotransposons (PCRBr). Three copies of the CRB were identified in one BAC clone as nested insertions within a tandem array of 24 copies of a 176 bp centromeric repeat, CentBr. A complex mosaic structure consisting of nine PCRBr elements and large blocks of 238 bp degenerate tandem repeats (TR238) were found in or near a derivative of 5S-25S rDNA sequences. The chromosomal positions of selected repeats were determined using in situ hybridization. These revealed that CRB is a major component of all centromeres in three diploid Brassica species and their allotetraploid relatives. However, CentBr was not detected in the most distantly related of the diploid species analyzed, B. nigra. PCRBr and TR238 were found to be major components in the peri-centromeric heterochromatin blocks of four chromosomes of B. rapa. These repetitive elements were not identified in B. oleracea or B. nigra, indicating that they are A-genome-specific. GenBank accession numbers: KBrH001P13 (AC 166739); KBrH015B20 (AC 166740); end sequences of KBrH BAC library (CW 978640 - CW 988843); end sequences of KBrS BAC library (DU 826965 - DU 835595); end sequences of KBrB BAC library (DX 010661 - DX 083363). 相似文献
955.
Kim HM Hong SH Kim MS Lee CW Kang JS Lee K Park SK Han JW Lee HY Choi Y Kwon HJ Han G 《Bioorganic & medicinal chemistry letters》2007,17(22):6234-6238
Novel delta-lactam-based HDAC inhibitors which have various substituted benzyl, bi-aromatic cap groups were prepared using ring closure metathesis reaction, and evaluated their HDAC inhibitory activities and anti-proliferative effects. Among prepared analogues, 11m and 11o have very strong HDAC enzymatic inhibition and showed the most potent growth inhibitory activity to five human tumor cell lines including PC-3, ACHN, NUGC-3, HCT-15, and MBA-MB-231 tumor cell lines. Compounds 11m and 11o also showed good tumor growth inhibition of MDA-MB-231 cells in in vivo xenograft model. Structure-activity relationship study using docking model explained the significance of hydrophobic aromatic cap groups for their in vitro activities. 相似文献
956.
Chung JU Kim SY Lim JO Choi HK Kang SU Yoon HS Ryu H Kang DW Lee J Kang B Choi S Toth A Pearce LV Pavlyukovets VA Lundberg DJ Blumberg PM 《Bioorganic & medicinal chemistry》2007,15(18):6043-6053
A series of alpha-substituted N-(4-tert-butylbenzyl)-N'-[4-(methylsulfonylamino)benzyl]thiourea analogues have been investigated as TRPV1 receptor antagonists. alpha-Methyl substituted analogues showed potent and stereospecific antagonism to the action of capsaicin on rat TRPV1 heterologously expressed in Chinese hamster ovary cells. In particular, compounds 14 and 18, which possess the R-configuration, exhibited excellent potencies (respectively, K(i)=41 and 39.2 nM and K(i(ant))=4.5 and 37 nM). 相似文献
957.
958.
Gao Q Mezei G Nie Y Rao Y Choi CS Bechmann I Leranth C Toran-Allerand D Priest CA Roberts JL Gao XB Mobbs C Shulman GI Diano S Horvath TL 《Nature medicine》2007,13(1):89-94
Metabolic hormones, such as leptin, alter the input organization of hypothalamic circuits, resulting in increased pro-opiomelanocortin (POMC) tone, followed by decreased food intake and adiposity. The gonadal steroid estradiol can also reduce appetite and adiposity, and it influences synaptic plasticity. Here we report that estradiol (E2) triggers a robust increase in the number of excitatory inputs to POMC neurons in the arcuate nucleus of wild-type rats and mice. This rearrangement of synapses in the arcuate nucleus is leptin independent because it also occurred in leptin-deficient (ob/ob) and leptin receptor-deficient (db/db) mice, and was paralleled by decreased food intake and body weight gain as well as increased energy expenditure. However, estrogen-induced decrease in body weight was dependent on Stat3 activation in the brain. These observations support the notion that synaptic plasticity of arcuate nucleus feeding circuits is an inherent element in body weight regulation and offer alternative approaches to reducing adiposity under conditions of failed leptin receptor signaling. 相似文献
959.
Renal clearance of quantum dots 总被引:9,自引:0,他引:9
Choi HS Liu W Misra P Tanaka E Zimmer JP Itty Ipe B Bawendi MG Frangioni JV 《Nature biotechnology》2007,25(10):1165-1170
The field of nanotechnology holds great promise for the diagnosis and treatment of human disease. However, the size and charge of most nanoparticles preclude their efficient clearance from the body as intact nanoparticles. Without such clearance or their biodegradation into biologically benign components, toxicity is potentially amplified and radiological imaging is hindered. Using intravenously administered quantum dots in rodents as a model system, we have precisely defined the requirements for renal filtration and urinary excretion of inorganic, metal-containing nanoparticles. Zwitterionic or neutral organic coatings prevented adsorption of serum proteins, which otherwise increased hydrodynamic diameter by >15 nm and prevented renal excretion. A final hydrodynamic diameter <5.5 nm resulted in rapid and efficient urinary excretion and elimination of quantum dots from the body. This study provides a foundation for the design and development of biologically targeted nanoparticles for biomedical applications. 相似文献
960.
Previous studies have established that chlorpyrifos (CPS), fipronil, and nonane can all be metabolized by human liver microsomes (HLM) and a number of cytochrome P450 (CYP) isoforms. However, metabolic interactions between these three substrates have not been described. In this study the effect of either coincubation or preincubation of CPS with HLM or CYP isoforms with either fipronil or nonane as substrate was investigated. In both co- and preincubation experiments, CPS significantly inhibited the metabolism of fipronil or nonane by HLM although CPS inhibited the metabolism of fipronil more effectively than that of nonane. CPS significantly inhibited the metabolism of fipronil by CYP3A4 as well as the metabolism of nonane by CYP2B6. In both cases, preincubation with CPS caused greater inhibition than coincubation, suggesting that the inhibition is mechanism based. 相似文献