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211.
212.
Chen SB Tan JH Ou TM Huang SL An LK Luo HB Li D Gu LQ Huang ZS 《Bioorganic & medicinal chemistry letters》2011,21(3):1004-1009
Discovery of potent and selective ligands for telomeric G-quadruplex DNA is a challenging work. Through a combination approach of pharmacophore model construction, model validation, database virtual screening, chemical synthesis and interaction evaluation, we discovered and confirmed triaryl-substituted imidazole TSIZ01 to be a new telomeric G-quadruplex ligand with potent binding and stabilizing activity to G-quadruplex DNA, as well as a 8.7-fold selectivity towards telomeric G-quadruplex DNA over duplex DNA. 相似文献
213.
214.
An isochorismate-pyruvate lyase with adventitious chorismate mutase activity from Pseudomonas aerugionsa (PchB) achieves catalysis of both pericyclic reactions in part by the stabilization of reactive conformations and in part by electrostatic transition-state stabilization. When the active site loop Lys42 is mutated to histidine, the enzyme develops a pH dependence corresponding to a loss of catalytic power upon deprotonation of the histidine. Structural data indicate that the change is not due to changes in active site architecture, but due to the difference in charge at this key site. With loss of the positive charge on the K42H side chain at high pH, the enzyme retains lyase activity at ~100-fold lowered catalytic efficiency but loses detectable mutase activity. We propose that both substrate organization and electrostatic transition state stabilization contribute to catalysis. However, the dominant reaction path for catalysis is dependent on reaction conditions, which influence the electrostatic properties of the enzyme active site amino acid side chains. 相似文献
215.
Abscisic acid plays an important role in the regulation of strawberry fruit ripening 总被引:10,自引:0,他引:10
The plant hormone abscisic acid (ABA) has been suggested to play a role in fruit development, but supporting genetic evidence has been lacking. Here, we report that ABA promotes strawberry (Fragaria ananassa) fruit ripening. Using a newly established Tobacco rattle virus-induced gene silencing technique in strawberry fruit, the expression of a 9-cis-epoxycarotenoid dioxygenase gene (FaNCED1), which is key to ABA biosynthesis, was down-regulated, resulting in a significant decrease in ABA levels and uncolored fruits. Interestingly, a similar uncolored phenotype was observed in the transgenic RNA interference (RNAi) fruits, in which the expression of a putative ABA receptor gene encoding the magnesium chelatase H subunit (FaCHLH/ABAR) was down-regulated by virus-induced gene silencing. More importantly, the uncolored phenotype of the FaNCED1-down-regulated RNAi fruits could be rescued by exogenous ABA, but the ABA treatment could not reverse the uncolored phenotype of the FaCHLH/ABAR-down-regulated RNAi fruits. We observed that down-regulation of the FaCHLH/ABAR gene in the RNAi fruit altered both ABA levels and sugar content as well as a set of ABA- and/or sugar-responsive genes. Additionally, we showed that exogenous sugars, particularly sucrose, can significantly promote ripening while stimulating ABA accumulation. These data provide evidence that ABA is a signal molecule that promotes strawberry ripening and that the putative ABA receptor, FaCHLH/ABAR, is a positive regulator of ripening in response to ABA. 相似文献
216.
217.
B. Wang Y. Zheng H. Shi X. Du Y. Zhang B. Wei M. Luo H. Wang X. Wu X. Hua M. Sun X. Xu 《Genes, Brain & Behavior》2017,16(2):296-307
Zfp462 is a newly identified vertebrate‐specific zinc finger protein that contains nearly 2500 amino acids and 23 putative C2H2‐type zinc finger domains. So far, the functions of Zfp462 remain unclear. In our study, we showed that Zfp462 is expressed predominantly in the developing brain, especially in the cerebral cortex and hippocampus regions from embryonic day 7.5 to early postnatal stage. By using a piggyBac transposon‐generated Zfp462 knockout (KO) mouse model, we found that Zfp462 KO mice exhibited prenatal lethality with normal neural tube patterning, whereas heterozygous (Het) Zfp462 KO (Zfp462+/?) mice showed developmental delay with low body weight and brain weight. Behavioral studies showed that Zfp462+/? mice presented anxiety‐like behaviors with excessive self‐grooming and hair loss, which were similar to the pathological grooming behaviors in Hoxb8 KO mice. Further analysis of grooming microstructure showed the impairment of grooming patterning in Zfp462+/? mice. In addition, the mRNA levels of Pbx1 (pre‐B‐cell leukemia homeobox 1, an interacting protein of Zfp462) and Hoxb8 decreased in the brains of Zfp462+/? mice, which may be the cause of anxiety‐like behaviors. Finally, imipramine, a widely used and effective anti‐anxiety medicine, rescued anxiety‐like behaviors and excessive self‐grooming in Zfp462+/? mice. In conclusion, Zfp462 deficiency causes anxiety‐like behaviors with excessive self‐grooming in mice. This provides a novel genetic mouse model for anxiety disorders and a useful tool to determine potential therapeutic targets for anxiety disorders and screen anti‐anxiety drugs. 相似文献
218.
Haitao Luo Stephen B. Cox Weimin Gao Jiahua Yu Lili Tang Jia-Sheng Wang 《Metabolomics : Official journal of the Metabolomic Society》2006,2(4):235-241
Green tea polyphenols (GTP) effectively protect against chronic diseases in various animal models but human studies have been
inconclusive. GTP components and metabolites in body fluids have been suggested as potential biomarkers, but validation of
these biomarkers has rarely been done in human populations. A randomized, double-blinded, and placebo-controlled phase IIa
chemoprevention study with GTP was conducted in 120 human subjects for 3 months. To validate GTP biomarker profiles, plasma
samples were collected at baseline, 1-month, and 3-month and were analyzed by HPLC-Coularray electrochemical detection (ECD)
for specific GTP components as well as for non-targeted metabolites. The levels of 2 GTP components, epigallocatechin-3-gallate
(EGCG) and epicatechin-3-gallate (ECG), were homogenous at baseline (p > 0.45) but were significantly elevated (p < 0.01) by GTP treatment. Metabolic profiling identified 106 metabolites, and 56 of them were chosen to construct discriminant
functions (DFs) based on the data at 3 months. The DFs clearly separated the placebo, 500 mg GTP, and 1000 mg GTP groups with
an accuracy rate of 97.3%. When the DFs were applied to the combined baseline and 1-month data, the accuracy rate was 62.9%
in classifying subjects into the 3 intervention groups. DFs derived from 1-month data showed similar results. Overall, this
study validated plasma EGCG and ECG as reliable biomarkers for GTP consumption, and found metabolic profiles effective in
discriminating different GTP dosages. 相似文献
219.
We studied the structures of the cerebellar cortex of young adult and old cats for age-related changes, which were statistically
analysed. Nissl staining was used to visualize the cortical neurons. The immunohistochemical method was used to display glial
fibrillary acidic protein (GFAP)-immunoreactive (IR) astrocytes and neurofilament-immunoreactive (NF-IR) neurons. Under the
microscope, the thickness of the cerebellar cortex was measured; and the density of neurons in all the layers as well as that
of GFAP-IR cells in the granular layer was analysed. Compared with young adult cats, the thickness of the molecular layer
and total cerebellar cortex was significantly decreased in old cats, and that of the granular layer increased. The density
of neurons in each layer was significantly lower in old cats than in young adult ones. Astrocytes in old cats were significantly
denser than in young adult ones, and accompanied by evident hypertrophy of the cell bodies and enhanced immunoreaction of
GFAP substance. Purkinje cells (PCs) in old cats showed much fewer NF-IR dendrites than those in young adults. The above findings
indicate a loss of neurons and decrease in the number of dendrites of the PCs in the aged cerebellar cortex, which might underlie
the functional decline of afferent efficacy and information integration in the senescent cerebellum. An age-dependent enhancement
of activity of the astrocytes may exert a protective effect on neurons in the aged cerebellum 相似文献
220.