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911.
912.
Follistatin-like 1 suppresses sensory afferent transmission by activating Na+,K+-ATPase 总被引:1,自引:0,他引:1
Li KC Zhang FX Li CL Wang F Yu MY Zhong YQ Zhang KH Lu YJ Wang Q Ma XL Yao JR Wang JY Lin LB Han M Zhang YQ Kuner R Xiao HS Bao L Gao X Zhang X 《Neuron》2011,69(5):974-987
Excitatory synaptic transmission is modulated by inhibitory neurotransmitters and neuromodulators. We found that the synaptic transmission of somatic sensory afferents can be rapidly regulated by a presynaptically secreted protein, follistatin-like 1 (FSTL1), which serves as a direct activator of Na(+),K(+)-ATPase (NKA). The FSTL1 protein is highly expressed in small-diameter neurons of the dorsal root ganglion (DRG). It is transported to axon terminals via small translucent vesicles and secreted in both spontaneous and depolarization-induced manners. Biochemical assays showed that FSTL1 binds to the α1 subunit of NKA and elevates NKA activity. Extracellular FSTL1 induced membrane hyperpolarization in cultured cells and inhibited afferent synaptic transmission in spinal cord slices by activating NKA. Genetic deletion of FSTL1 in small DRG neurons of mice resulted in enhanced afferent synaptic transmission and sensory hypersensitivity, which could be reduced by intrathecally applied FSTL1 protein. Thus, FSTL1-dependent activation of NKA regulates the threshold of somatic sensation. 相似文献
913.
Penicillium expansum lipase (PEL) was used to catalyze biodiesel production from corn oil in [BMIm][PF6]1 (an ionic liquid, IL) and tert-butanol. Both systems were optimized in terms of MeOH/oil molar ratio, reaction temperature, enzyme loading, solvent volume, and water content. The high conversion obtained in the IL (86%) as compared to that in tert-butanol (52%) demonstrates that the IL is a superior solvent for PEL-catalyzed biodiesel production. Poor yields were obtained in a series of hydrophilic ILs. Addition of salt hydrates affected biodiesel production predominantly through the specific ion (Hofmeister) effect. The impact of methanol on both activity and stability of PEL in the IL and in hexane was investigated, in comparison to the results obtained by two commonly used lipases, Novozym 435 and Lipozyme TLIM. The results substantiate that while different lipases show different resistance to methanol in different reaction systems, PEL is tolerant to methanol in both systems. 相似文献
914.
Ustilago maydis is known to produce glycolipid-type biosurfactants. Here, we show that U. maydis is able to efficiently convert biodiesel-derived crude glycerol to glycolipids. We have optimized the medium composition and environmental factors for bioconversion of crude glycerol to glycolipids. The synthetic medium (MinCG) contains 50 g L−1 crude glycerol and 20.3 mg L−1 ammonium citrate as the carbon and nitrogen sources, respectively. The supplementation of trace amount of amino acids, Group-B vitamins and precursors of glycolipids, mannose and erythritol, also improved the final yield. At pH 4.0 and 30 °C, 32.1 g L−1 total glycolipids was produced in a 8.2-day fed-batch bioprocess. Methanol at 2% or above severely inhibited cell growth and production of glycolipids. Our results suggest that U. maydis is an excellent host for the bioconversion of crude glycerol to value-added products. 相似文献
915.
Hoffmann TJ Kvale MN Hesselson SE Zhan Y Aquino C Cao Y Cawley S Chung E Connell S Eshragh J Ewing M Gollub J Henderson M Hubbell E Iribarren C Kaufman J Lao RZ Lu Y Ludwig D Mathauda GK McGuire W Mei G Miles S Purdy MM Quesenberry C Ranatunga D Rowell S Sadler M Shapero MH Shen L Shenoy TR Smethurst D Van den Eeden SK Walter L Wan E Wearley R Webster T Wen CC Weng L Whitmer RA Williams A Wong SC Zau C Finn A Schaefer C Kwok PY Risch N 《Genomics》2011,98(2):79-89
The success of genome-wide association studies has paralleled the development of efficient genotyping technologies. We describe the development of a next-generation microarray based on the new highly-efficient Affymetrix Axiom genotyping technology that we are using to genotype individuals of European ancestry from the Kaiser Permanente Research Program on Genes, Environment and Health (RPGEH). The array contains 674,517 SNPs, and provides excellent genome-wide as well as gene-based and candidate-SNP coverage. Coverage was calculated using an approach based on imputation and cross validation. Preliminary results for the first 80,301 saliva-derived DNA samples from the RPGEH demonstrate very high quality genotypes, with sample success rates above 94% and over 98% of successful samples having SNP call rates exceeding 98%. At steady state, we have produced 462 million genotypes per week for each Axiom system. The new array provides a valuable addition to the repertoire of tools for large scale genome-wide association studies. 相似文献
916.
Zhao X Yu Z Dai W Yao Z Zhou W Zhou W Zhou J Yang Y Zhu Y Chen S Cao L 《Biotechnology and applied biochemistry》2011,58(6):405-411
Antibody-therapeutic agent conjugation to be delivered specifically to tumor cells is required for many target-based therapeutic strategies. In the present study, a recombinant immunotoxin was constructed by which melittin was fused to an anti-asialoglycoprotein receptor (ASGPR) single-chain variable fragment antibody (C1), and targeting ability and cytolytic efficacy of the fusion protein were studied. Our results suggested that the recombinant 29.4 kDa protein C1M was expressed in Escherichia coli as a soluble style. Binding of C1M to the surface of hepatocellular carcinoma (HCC) cells was confirmed by both immunohistochemistry and flow cytometry assays. C1M kept the hemolytic activity of melittin and exhibited cytolytic capacity to HepG2 cells at a concentration of 1.5 μg/mL, under which erythrocytes would not be lysed. The effects were greatly inhibited by coadministration with asialoorosomucoid, a natural ligand for ASGPR. These results suggested that C1M conferred targeting and ASGPR-specific cytotoxicity to HCC cells. This work makes it possible to further investigate its antihepatoma efficacy in vivo. 相似文献
917.
Zhao Q Xie R Zhang T Fang J Mei X Ning J Tang Y 《Bioorganic & medicinal chemistry letters》2011,21(21):6404-6408
Homo- and hetero-dimers of inactive organophosphorous group(s) dramatically enhanced the acetylcholinesterase (AChE; EC 3.1.1.7) inhibiting potency, with the highest potency observed at a tether length of 6 methylene groups (6d) for the homodimers, and 7 methylene groups (8e) for the heterodimers. The docking model of Drosophila melanogaster AChE suggested that 6d and 8e bound at the catalytic and peripheral sites of AChE, in which two organophosphorous groups of 6d individually oriented towards TRP83 of catalytic sites and TRP321 of peripheral sites, and phthalicimide group of 8e was appropriately arranged for a π-π interaction with the phenyl ring of TYR330, furthermore, the organophosphorous group introduced hydrophobic interaction with TRP83. The compounds prepared in this work demonstrated high insecticidal activity to Lipaphis erysimi and Tetranychus cinnbarinus at the concentration 300mg/L. 相似文献
918.
Gao J Li X Gu G Sun B Cui M Ji M Lou HX 《Bioorganic & medicinal chemistry letters》2011,21(2):622-627
To investigate the relationship of cytotoxicity and saponins with varied aglycones, based on the structure of indioside E 1, a natural derived anti-tumor active ingredient from Chinese medicinal plant Solanum indicum L., five novel saponins 2-6 bearing the same trisaccharide moiety together with 1 were efficiently synthesized via a transglycosylation strategy. MTT assay revealed the killing effects to tumor cells of the synthesized saponins are varied with the change of aglycones. Furthermore, time-lapse microscopy, LDH release, PI staining, and immunocytochemical investigations demonstrated that the cell death caused by neosaponin 2 was through oncotic necrosis involving plasma membrane perturbation and destruction of cytoskeleton. 相似文献
919.
Zheng C Cao G Xia M Feng H Glenn J Anand R Zhang K Huang T Wang A Kong L Li M Galya L Hughes RO Devraj R Morton PA Rogier DJ Covington M Baribaud F Shin N Scherle P Diamond S Yeleswaram S Vaddi K Newton R Hollis G Friedman S Metcalf B Xue CB 《Bioorganic & medicinal chemistry letters》2011,21(5):1442-1446
We report the discovery of a potent, selective, and orally bioavailable dual CCR2 and CCR5 antagonist (3S,4S)-N-[(1R,3S)-3-isopropyl-3-({4-[4-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl}carbonyl)cyclopentyl]-3-methoxytetrahydro-2H-pyran-4-amine (19). After evaluation in 28-day toxicology studies, compound 19 (INCB10820/PF-4178903) was selected as a clinical candidate. 相似文献
920.
Wang T Ioannidis S Almeida L Block MH Davies AM Lamb ML Scott DA Su M Zhang HJ Alimzhanov M Bebernitz G Bell K Zinda M 《Bioorganic & medicinal chemistry letters》2011,21(10):2958-2961
Synthesis and biological evaluation of a series of 6-aminopyrazolyl-pyridine-3-carbonitriles as JAK2 kinase inhibitors was reported. Biochemical screening, followed by profile optimization, resulted in JAK2 inhibitors exhibiting good kinase selectivity, pharmacokinetic properties, physical properties and pharmacodynamic effects. 相似文献