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1.
CRA13; a peripheral dual CB1R/CB2R agonist with clinically proven analgesic properties, infiltrates into CNS producing adverse effects due to central CB1R agonism. Such adverse effects might be circumvented by less lipophilic compounds with attenuated CB1R affinity. Metabolism produces less lipophilic metabolites that might be active metabolites. Some CRA13 oxidative metabolites and their analogues were synthesized as less lipophilic CRA13 analogues. Probing their CB1R and CB2R activity revealed the alcohol metabolite 8c as a more potent and more effective CB2R ligand with attenuated CB1R affinity relative to CRA13. Also, the alcohol analogue 8b and methyl ester 12a possessed enhanced CB2R affinity and reduced CB1R affinity. The CB2R binding affinity of alcohol analogue 8b was similar to CRA13 while that of methyl ester 12a was more potent. In silico study provided insights into the possible molecular interactions that might explain the difference in the elicited biological activity of these compounds.  相似文献   
2.
The NS neurons are nonspiking cells, present as pairs in each midbody ganglion of the leech nervous system, which display a very extensive arborization. They were shown to regulate the coactivation of motoneurons. Here we have investigated the electrophysiological properties of these neurons under the hypothesis that transmission along the extensive neurites requires the aid of voltage-dependent conductances. The results indicate that NS neurons respond to electrical stimulation with a spike-like event, which was not an all-or-none but rather a graded phenomenon that depended on the intensity and duration of the electrical stimulus. The spike-like response was activated at a membrane potential of approximately −50 mV; its amplitude was a logarithmic function of the extracellular Ca2+ concentration and was unaffected by a broad range of changes in the extracellular Na+ concentration; intracellular application of tetraethylammonium (TEA) caused a large increase in its amplitude and duration. These data indicate that NS neurons bear voltage-dependent low-threshold Ca2+ and TEA-sensitive K+ conductances that could contribute to shaping synaptic signals, or transmission along the extensive neuritic tree.  相似文献   
3.
Dong A  Ye M  Guo H  Zheng J  Guo D 《Biotechnology letters》2003,25(4):339-344
Of 49 microbial strains screened for their capabilities to transform ginsenoside Rb1, Rhizopus stolonifer and Curvularia lunata produced four key metabolites: 3-O-[-d-glucopyranosyl-(1,2)--d-glucopyranosyl]- 20-O-[-d-glucopyranosyl]-3,12, 20(S)-trihydroxydammar-24-ene (1), 3-O-[-d-glucopyranosyl-(1,2)--d- glucopyranosyl]-20-O-[-d-glucopyranosyl]-3,12, 20(S)-trihydroxydammar-24-ol (2), 3-O-[-d-gluco- pyranosyl-(1,2)--d-glucopyranosyl]-3, 12, 20(S)-trihydroxydammar-24-ene (3), and 3-O--d-glucopyranosyl-3, 12, 20(S)-trihydroxydammar-24-ene (4), identified by TOF-MS, 1H- and 13C-NMR spectral data. Metabolites 1, 3 and 4 were from the incubation with R. stolonifer, and 1 and 2 from the incubation with C. lunata. Compound 2 was identified as a new compound.  相似文献   
4.
Liang A  Sha J  Lu W  Chen M  Li L  Jin D  Yan Y  Wang J  Ping S  Zhang W  Wang Y  Lin M 《Biotechnology letters》2008,30(8):1397-1401
A novel class II 5-enoylpyruvylshikimate-3-phosphate synthase (EPSPS) was identified from Pseudomonas stutzeri A1501 by complementation of an Escherichia coli auxotrophic aroA mutant. The single amino acid substitution of serine (Ser) for asparagine (Asn)-130 of the A1501 EPSPS enhanced resistance to 200 mM glyphosate. The mutated EPSPS had a 2.5-fold increase for IC(50) [glyphosate] value, a 2-fold increase for K (i) [glyphosate] value, but a K (m) [PEP] value similar to that of wild type. The effect of the single residue mutation on glyphosate resistance was also analyzed using a computer-based three-dimensional model.  相似文献   
5.
Marine scallops, with extended planktonic larval stages which can potentially disperse over large distances when advected by marine currents, are expected to possess low geographical differentiation. However, the sessile lifestyle as adult tends to form discrete "sea beds" with unique population dynamics and structure. The narrow distribution of Zhikong scallop (Chlamys farreri), its long planktonic larval stage, and the extremely hydrographic complexity in its distribution range provide an interesting case to elucidate the impact of marine currents on geographical differentiation for marine bivalves at a fine geographical scale. In this study, we analyzed genetic variation at nine microsatellite DNA loci in six locations throughout the distribution of Zhikong scallop in the Northern China. Very high genetic diversity was present in all six populations. Two populations sampled from the same marine gyre had no detectable genetic differentiation (F (ST) = 0.0013); however, the remaining four populations collected from different marine gyres or separated by strong marine currents showed low but significant genetic differentiation (F (ST) range 0.0184-0.0602). Genetic differentiation was further analyzed using the Monmonier algorithm to identify genetic barriers and using the assignment test conducted by software GeneClass2 to ascertain population membership of individuals. The genetic barriers fitting the orientation of marine gyres/currents were clearly identified, and the individual assignment analysis indicated that 95.6% of specimens were correctly allocated to one of the six populations sampled. The results support the hypothesis that significant population structure is present in Zhikong scallop at a fine geographical scale, and marine currents can be responsible for the genetic differentiation.  相似文献   
6.
The interconnection network is one of the key architectural components in any parallel computer. The distribution of the traffic injected into the network is among the factors that greatly influences network performance. The uniform traffic pattern has been adopted in many existing network performance evaluation studies due to the tractability of the resulting analytical modelling approach. However, many real applications exhibit non-uniform traffic patterns such as hot-spot traffic. K-ary n-cubes have been the mostly widely used in the implementation of practical parallel systems. Extensive research studies have been conducted on the performance modelling and evaluation of these networks. Nonetheless, most of these studies have been confined to uniform traffic distributions and have been based on software simulation. The present paper proposes a new stochastic model to predict message latency in k-ary n-cubes with deterministic routing in the presence of hot-spot traffic. The model has been validated through simulation experiments and has shown a close agreement with simulation results.
Geyong MinEmail:
  相似文献   
7.
Fragile X syndrome, the most common form of inherited mental retardation, is caused by the absence of the RNA-binding protein fragile X mental retardation protein (FMRP). FMRP regulates local protein synthesis in dendritic spines. Dopamine (DA) is involved in the modulation of synaptic plasticity. Activation of DA receptors can regulate higher brain functions in a protein synthesis-dependent manner. Our recent study has shown that FMRP acts as a key messenger for DA modulation in forebrain neurons. Here, we demonstrate that FMRP is critical for DA D1 receptor-mediated synthesis of synapse-associated protein 90/PSD-95-associated protein 3 (SAPAP3) in the prefrontal cortex (PFC). DA D1 receptor stimulation induced dynamic changes of FMRP phosphorylation. The changes in FMRP phosphorylation temporally correspond with the expression of SAPAP3 after D1 receptor stimulation. Protein phosphatase 2A, ribosomal protein S6 kinase, and mammalian target of rapamycin are the key signaling molecules for FMRP linking DA D1 receptors to SAPAP3. Knockdown of SAPAP3 did not affect surface expression of α-amino-3-hydroxyl-5-methyl-4-isoxazole-4-propionate (AMPA) GluR1 receptors induced by D1 receptor activation but impaired their subsequent internalization in cultured PFC neurons; the subsequent internalization of GluR1 was also impaired in Fmr1 knock-out PFC neurons, suggesting that FMRP may be involved in subsequent internalization of GluR1 through regulating the abundance of SAPAP3 after DA D1 receptor stimulation. Our study thus provides further insights into FMRP involvement in DA modulation and may help to reveal the molecular mechanisms underlying impaired learning and memory in fragile X syndrome.  相似文献   
8.

Objectives

The primary aim of this research was to investigate the wear behavior and wear mechanism of five different veneering porcelains.

Methods

Five kinds of veneering porcelains were selected in this research. The surface microhardness of all the samples was measured with a microhardness tester. Wear tests were performed on a ball-on-flat PLINT fretting wear machine, with lubrication of artificial saliva at 37°C. The friction coefficients were recorded by the testing system. The microstructure features, wear volume, and damage morphologies were recorded and analyzed with a confocal laser scanning microscope and a scanning electron microscope. The wear mechanism was then elucidated.

Results

The friction coefficients of the five veneering porcelains differ significantly. No significant correlation between hardness and wear volume was found for these veneering porcelains. Under lubrication of artificial saliva, the porcelain with higher leucite crystal content exhibited greater wear resistance. Additionally, leucite crystal size and distribution in glass matrix influenced wear behavior. The wear mechanisms for these porcelains were similar: abrasive wear dominates the early stage, whereas delamination was the main damage mode at the later stage. Furthermore, delamination was more prominent for porcelains with larger crystal sizes.

Significance

Wear compatibility between porcelain and natural teeth is important for dental restorative materials. Investigation on crystal content, size, and distribution in glass matrix can provide insight for the selection of dental porcelains in clinical settings.  相似文献   
9.
    
Kaposi sarcoma-associated herpesvirus (KSHV) has a causative role in several human malignancies. KSHV latency-associated nuclear antigen (LANA) mediates persistence of viral episomes in latently infected cells. LANA mediates KSHV DNA replication and segregates episomes to progeny nuclei. The structure of the LANA DNA binding domain was recently solved, revealing a positive electrostatic patch opposite the DNA binding surface, which is the site of BET protein binding. Here we investigate the functional role of the positive patch in LANA-mediated episome persistence. As expected, LANA mutants with alanine or glutamate substitutions in the central, peripheral, or lateral portions of the positive patch maintained the ability to bind DNA by EMSA. However, all of the substitution mutants were deficient for LANA DNA replication and episome maintenance. Mutation of the peripheral region generated the largest deficiencies. Despite these deficiencies, all positive patch mutants concentrated to dots along mitotic chromosomes in cells containing episomes, similar to LANA. The central and peripheral mutants, but not the lateral mutants, were reduced for BET protein interaction as assessed by co-immunoprecipitation. However, defects in BET protein binding were independent of episome maintenance function. Overall, the reductions in episome maintenance closely correlated with DNA replication deficiencies, suggesting that the replication defects account for the reduced episome persistence. Therefore, the electrostatic patch exerts a key role in LANA-mediated DNA replication and episome persistence and may act through a host cell partner(s) other than a BET protein or by inducing specific structures or complexes.  相似文献   
10.
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