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111.
SIRT6 is a histone deacetylase that has been proposed as a potential therapeutic target for metabolic disorders and the prevention of age-associated diseases. Thus, the identification of compounds that modulate SIRT6 activity could be of great therapeutic importance. The aim of this study was to develop a screening method for the identification of novel modulators of SIRT6 from a natural plant extract. We immobilized SIRT6 onto the surface of magnetic beads, and assessed SIRT6 enzymatic activity on synthetic acetylated histone tails (H3K9Ac) by measuring products of the deacetylation process. The SIRT6 coated magnetic beads were then suspended in fenugreek seed extract (Trigonella foenum-graecum) as a bait to identify active ligands that suppress SIRT6 activity. While the entire extract also inhibited SIRT6 activity in a cell-based assay, the inhibitory effect of two flavonoids from this extract, quercetin and vitexin, was only detected in vitro. This is the first report on the use of protein-coated magnetic beads for the identification of an active ligand from a botanical matrix, and it sets the basis for the de novo identification of SIRT6 modulators from complex biological mixtures. 相似文献
112.
Printed Electronics: Room‐Temperature Printing of Organic Thin‐Film Transistors with π‐Junction Gold Nanoparticles (Adv. Funct. Mater. 31/2014) 下载免费PDF全文
113.
K Kameo K Takeshita Y Yasuda K Matsumoto K Tomisawa 《Canadian Metallurgical Quarterly》1996,44(3):602-604
2-Acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanonic acid (KE-298) is an antirheumatic agent. To elucidate the effects of optically active KE-298, we resolved the racemic acid and obtained the two optical isomers. (+)-KE-298 was converted to the 4-bromobenzyl ester derivative and the absolute structure was confirmed as (S) by X-ray crystallographic analysis. The pharmacological activities of the optical isomers and racemic KE-298 were compared by using the characteristic tests for KE-298. Though (+)-KE-298 showed a stronger suppressive effect on rat adjuvant arthritis than (-)-KE-298, no difference between the two isomers was detected in in vitro tests (enhancing effect on lymphocyte transformation, IL-1 antagonistic effect). 相似文献
114.
H Yasuda MA Lindorfer KA Woodfork JE Fletcher JC Garrison 《Canadian Metallurgical Quarterly》1996,271(31):18588-18595
The coupling of receptors to heterotrimeric G proteins is determined by interactions between the receptor and the G protein alpha subunits and by the composition of the betagamma dimers. To determine the role of the gamma subunit prenyl modification in this interaction, the CaaX motifs in the gamma1 and gamma2 subunits were altered to direct modification with different prenyl groups, recombinant betagamma dimers expressed in the baculovirus/Sf9 insect cell system, and the dimers purified. The activity of the betagamma dimers was compared in two assays: formation of the high affinity agonist binding conformation of the A1 adenosine receptor and receptor-catalyzed exchange of GDP for GTP on the alpha subunit. The beta1gamma1 dimer (modified with farnesyl) was significantly less effective than beta1gamma2 (modified with geranylgeranyl) in either assay. The beta1gamma1-S74L dimer (modified with geranylgeranyl) was nearly as effective as beta1gamma2 in either assay. The beta1gamma2-L71S dimer (modified with farnesyl) was significantly less active than beta1gamma2. Using 125I-labeled betagamma subunits, it was determined that native and altered betagamma dimers reconstituted equally well into Sf9 membranes containing A1 adenosine receptors. These data suggest that the prenyl group on the gamma subunit is an important determinant of the interaction between receptors and G protein gamma subunits. 相似文献
115.
116.
This paper describes a multibit bandpass ΔΣ modulator (DSM) for a frequency-interleaved analog-to-digital (A/D) converter (ADC). A frequency-interleaved ADC using low oversampling ratio (OSR) DSMs is an attractive approach for broadband and high resolution A/D conversion. A multibit DSM is suitable for low-oversampling operation; however, the overall resolution of a multibit DSM is restricted by the accuracy of the internal D/A converter (DAC). Some methods have been reported for improving the internal DAC accuracy of a low-pass DSM, but no bandpass-shaping technique applicable to a bandpass DSM has been implemented, although some methods have been proposed by using simulation. This paper proposes a multibit bandpass DSM with bandpass noise-shaping dynamic element matching (BPNSDEM), which enables bandpass shaping to mismatch error of the internal DAC, and presents its implementation. The modulator was implemented in a 0.25-μm CMOS technology. It operates at a 2.5-V power supply and achieves a signal-to-noise ratio of 77.4 dB over a 250-kHz bandwidth centered at 566 kHz 相似文献
117.
R Sakakibara T Hattori K Kita K Arai T Yamanishi K Yasuda 《Canadian Metallurgical Quarterly》1998,64(3):389-391
To better understand genetic alterations in atypical adenomatous hyperplasia (AAH) of the prostate, we examined the prevalence of allelic imbalance at 5 microsatellite polymorphic markers on chromosomes 7q31-35, 8p12-21, 8p22, 8q22.2, and 18q12.2 from 15 patients with AAH. DNA samples were obtained from formalin-fixed paraffin-embedded sections using tissue microdissection. We found allelic imbalance in 7 of 15 (47%) cases of AAH. Genetic changes that commonly occur in early prostatic carcinogenesis and prostate carcinoma are found in AAH. Current data provide evidence of a genetic link between some cases of AAH and carcinoma. 相似文献
118.
S Sasaki T Hashimoto N Obana H Yasuda Y Uehara M Maeda 《Canadian Metallurgical Quarterly》1998,8(9):1019-1022
New inhibitors have been designed for cdc2 kinase based on a multiple pseudosubstrate structure. The new inhibitors have three different structural components: 3,4-bis(indol-3-yl)maleimide, Ac-Cys-(Ser)-Pro-Lys-Lys-NHMe, and ethyloxy group between the two components. Inhibitory activities toward cdc2 and other protein kinases were investigated, and the compound (21) with Ac-Cys-Pro-Lys-Lys-NHMe connected with the triethylene glycol spacer exhibited the most potent inhibition with relatively high selectivity. 相似文献
119.
M Kinoshita R Okuda J Morikawa T Yasuda T Jotoku M Abe 《Canadian Metallurgical Quarterly》1998,19(4):252-254
OBJECTIVE: To establish whether diltiazem reduces subcutaneous calcinosis (SCC) in patients with systemic sclerosis (SSc), and whether this calcinosis is related to other signs or symptoms. METHODS: 47 patients with SSc were evaluated and divided into two groups according to the presence or absence of SCC. RESULTS: Among the 12 patients with SCC who were treated with diltiazem and had sequential hand radiographs (differential time between the two radiographs: 7.8+/-4 years), there was a slight radiological improvement in three patients only. More patients with SCC had anticentromere antibodies than patients without (p = 0.003), fewer had anti-Scl 70 antibodies (p = 0.01), more had telangiectasia and giant capillaries ( p + 0.04 and 0.048 respectively), and SCC patients had significantly fewer capillaries at the nailfold (p = 0.03). CONCLUSION: These results do not clearly indicate that diltiazem is effective in calcinosis associated with SSc. Among the patients with SSc, those who also had SCC exhibited a distinctive autoimmune profile and more severe cutaneous capillary injury than those without SCC. 相似文献
120.
T Majima K Yasuda N Yamamoto K Kaneda K Hayashi 《Canadian Metallurgical Quarterly》1994,22(6):821-829
Effects of partial and complete stress shielding on mechanical properties and histology of in situ frozen patellar tendons were studied in 120 mature female Japanese White rabbits that were divided into three groups: completely stress-shielded, partially stress-shielded, and sham-operated groups. In the former two groups, tendon tension was reduced to 0% and about 30% of normal force, respectively, with a polyester artificial ligament. Tensile tests were conducted on patella-patellar tendon-tibia complexes harvested 1, 2, 3, 6, or 12 weeks after surgery. Tensile strength significantly decreased compared with the sham group to 17% and 28% at 3 and 6 weeks, respectively, in the completely stress-shielded group, and to 54% and 63% at 3 and 12 weeks, respectively, in the partially stress-shielded group. Patellar tendon cross-sectional area significantly increased to 156% and 157% at 2 and 3 weeks, respectively, in the completely stress-shielded group and to 133% at 2 weeks in the partially stress-shielded group, compared with the sham group. Stress shielding significantly changed tensile strength, tangent modulus, and cross-sectional area of in situ frozen patellar tendon; these changes depended on degree of stress shielding. Histologic observations indicated that remodeling occurred in the patellar tendon while there were no cells in the fascicle. 相似文献