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排序方式: 共有282条查询结果,搜索用时 15 毫秒
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Epple R Azimioara M Russo R Xie Y Wang X Cow C Wityak J Karanewsky D Bursulaya B Kreusch A Tuntland T Gerken A Iskandar M Saez E Martin Seidel H Tian SS 《Bioorganic & medicinal chemistry letters》2006,16(21):5488-5492
A series of PPARdelta-selective agonists was investigated and optimized for a favorable in vivo pharmacokinetic profile. Isoxazole LCI765 (17d) was found to be a potent and selective PPARdelta agonist with good in vivo PK properties in mouse (C(max)=5.1 microM, t(1/2)=3.1 h). LCI765 regulated expression of genes involved in energy homeostasis in relevant tissues when dosed orally in C57BL6 mice. A co-crystal structure of compound LCI765 and the LBD of PPARdelta is discussed. 相似文献
263.
Tove M. I. E. Christensen John E. Nielsen Jette D. Kreiberg Preben Rasmussen Jørn D. Mikkelsen 《Planta》1998,206(4):493-503
Pectin methyl esterase (PME) from orange (Citrus sinensis L.) fruit peels has been purified by ammonium sulphate precipitation, and ion-exchange and gel-filtration chromatography.
Characterization of the enzyme revealed a 36-kDa protein with an isoelectric point >9, a pH optimum at 7 and temperature optimum
at 50 °C. The substrate specificity and kinetic experiments showed that the affinity of PME for pectin was highly dependent
on the degree of esterification (DE) of the pectin, with K
m values of 0.7 mg ml-1 for pectin with a DE of 70% and 17 mg ml-1 for pectin with a DE of 25%. The sequences of the NH2-terminal end of digested peptides from the mature protein were obtained. A DNA fragment of 501 bp was cloned by polymerase
chain reaction amplification using degenerate primers and was further used for screening of a cDNA library. Two cDNA clones
were isolated encoding PMEs of 584 amino acids and 362 amino acids, respectively, including a putative signal peptide. The
deduced amino acid sequence showed full identity to the sequenced peptides. Polyclonal antibodies raised against orange peel
PME were used for immunohistochemistry. The main localization of PMEs was in the outer cell layers of the juice vesicles,
in the outer cell layers of the lamellae between the segments and in the inner cell layers of the albedo in the peel. In-situ
hybridization showed that the mRNA is very abundant in the fruit and was found in the same cell layers as the native enzyme.
A very intensive staining for PME mRNA was also seen in the core and in the flavedo close to the oil glands.
Received: 15 November 1997 / Accepted: 7 April 1998 相似文献
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Induction of biohydrogenation of oleic acid in Bacillus cereus by increase in temperature 总被引:1,自引:0,他引:1
A system catalyzing the biohydrogenation of oleate to stearate is present in a strain of Bacillus cereus which has been incubated at 37°. but not at 20°. The appearance of the system is blocked by the addition of chloramphenicol or rifampin. These findings indicate the biohydrogenation system present in this organism is induced by an elevation in temperature. 相似文献
267.
Jon Henrik Laake Tove Anita Slyngstad Finn-Mogens mejda Haug Ole Petter Ottersen 《Journal of neurochemistry》1995,65(2):871-881
Abstract: The immunogold labeling for glutamate and glutamine was studied at the electron microscopic level in hippocampal slice cultures following inhibition of l -glutamine synthetase [ l -glutamate:ammonia ligase (ADP-forming); EC 6.3.1.2]. In control cultures, glutamate-like immunoreactivity was highest in terminals, intermediate in pyramidal cell bodies, and low in glial cells. Glutamine-like immunoreactivity was high in glial cells, intermediate in pyramidal cell bodies, and low in terminals. After inhibition of glutamine synthetase with l -methionine sulfoximine, glutamate-like immunoreactivity was reduced by 52% in terminals and increased nearly fourfold in glia. Glutamine-like immunoreactivity was reduced by 66% in glia following l -methionine sulfoximine, but changed little in other compartments. In cultures that were treated with both l -methionine sulfoximine and glutamine (1.0 m M ), glutamate-like immunoreactivity was maintained at control levels in terminals, whereas in glia glutamate-like immunoreactivity was increased and glutamine-like immunoreactivity was decreased to a similar extent as in cultures treated with l -methionine sulfoximine alone. We conclude that (a) glutamate accumulates in glia when the flux through glutamine synthetase is blocked, emphasizing the importance of this pathway for the handling of glutamate; and (b) glutamine is necessary for the maintenance of a normal level of glutamate in terminals, and neither reuptake nor de novo synthesis through pathways other than the glutaminase reaction is sufficient. 相似文献
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Thor Ueland Elisabeth Astrup Kari Otterdal Tove Lekva Jeshina Janardhanan John A. J. Prakash Kurien Thomas Annika E. Michelsen Pl Aukrust George M. Varghese Jan K. Dams 《PLoS neglected tropical diseases》2021,15(4)
BackgroundThe mechanisms that control local and systemic inflammation in scrub typhus have only been partially elucidated. The wingless (Wnt) signaling pathways are emerging as important regulators of inflammation and infection, but have not been investigated in scrub typhus.Methodology/Principal findingsPlasma levels of secreted Wnt antagonists (i.e. DKK-1, sFRP-3, WIF-1 and SOST) were analyzed in patients with scrub typhus (n = 129), patients with similar febrile illness without O. tsutsugamushi infection (n = 31), febrile infectious disease controls, and in healthy controls (n = 31) from the same area of South India, and were correlated to markers of inflammation, immune and endothelial cell activation as well as for their association with organ specific dysfunction and mortality in these patients. We found i) Levels of SOST and in particular sFRP-3 and WIF-1 were markedly increased and DKK-1 decreased in scrub typhus patients at admission to the hospital compared to healthy controls. ii) In recovering scrub typhus patients, SOST, sFRP-3 and WIF-1 decreased and DKK-1 increased. iii) SOST was positively correlated with markers of monocyte/macrophage and endothelial/vascular activation as well as with renal dysfunction and poor outcome iv) Finally, regulation of Wnt pathways by O. tsutsugamushi in vitro in monocytes and ex vivo in mononuclear cells isolated from patients with scrub typhus, as evaluated by gene expression studies available in public repositories, revealed markedly attenuated canonical Wnt signaling.Conclusions/SignificanceOur findings suggest that scrub typhus is characterized by attenuated Wnt signaling possibly involving dysregulated levels of several secreted pathway antagonists. The secreted Wnt antagonist SOST was strongly associated with renal dysfunction and poor prognosis in these patients. 相似文献
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