Activation of mammalian target of rapamycin contributes to pain nociception induced in rats by BmK I, a sodium channel-specific modulator

The mammalian target of rapamycin （mTOR） pathway is essential for maintenance of the sensitivity of certain adult sensory neurons. Here, we investigated whether the mTOR cascade is involved in scorpion envenomation-induced pain hypersensitivity in rats. The results showed that intraplantar injection of a neurotoxin from Buthus martensii Karsch, BmK I （10 pg）, induced the activation of mTOR, as well as its downstream molecules p70 ribosomal S6 protein kinase （p70 S6K） and eukaryotic initiation factor 4E-binding protein 1 （4E-BP1）, in lumbar 5-6 dorsal root ganglia neurons on both sides in rats. The activation peaked at 2 h and recovered 1 day after injection. Compared with the control group, the ratios of p-mTOR/p-p70 S6K/p-4E- BP1 in three types of neurons changed significantly. The cell typology of p-mTOR/p-p70 S6K/p-4E-BP1 immuno-reactive neurons also changed. Intrathecal administration of deforolimus, a specific inhibitor of mTOR, attenuated BmK I-induced pain responses （spontaneous flinching, paroxysmal pain-like behavior, and mechanical hypersensitivity）. Together, these results imply that the mTOR signaling pathway is mobilized by and contributes to experimental scorpion sting-induced pain.

Pharmacological kinetics of BmK AS, a sodium channel site 4-specific modulator on Na_v1.3

Objective In this study, the pharmacological kinetics of Buthus martensi Karsch （BmK） AS, a specific modulator of voltage-gated sodium channel site 4, was investigated on Nav1.3 expressed in Xenopus oocytes. Methods Two-electrode voltage clamp was used to record the whole-cell sodium current. Results The peak currents of Nav1.3 were depressed by BmK AS over a wide range of concentrations （10, 100, and 500 nmol/L）. Most remarkably, BmK AS at 100 nmol/L hyperpolarized the voltage-dependence and increased the voltage-sensitivity of steady-state activation/inactivation. In addition, BmK AS was capable of hyperpolarizing not only the fast inactivation but also the slow inactivation, with a greater preference for the latter. Moreover, BmK AS accelerated the time constant and increased the ratio of recovery in Nav1.3 at all concentrations. Conclusion This study provides direct evidence that BmK AS facilitates steady-state activation and inhibits slow inactivation by stabilizing both the closed and open states of the Nav1.3 channel, which might result from an integrative binding to two receptor sites on the voltage-gated sodium channels. These results may shed light on therapeutics against Nav1.3-targeted pathology.

Bayes estimation of residual life by fusing multisource information

Residual life estimation is essential for reliability engineering. Traditional methods may experience difficulties in estimating the residual life of products with high reliability, long life, and small sample. The Bayes model provides a feasible solution and can be a useful tool for fusing multisource information. In this study, a Bayes model is proposed to estimate the residual life of products by fusing expert knowledge, degradation data, and lifetime data. The linear Wiener process is used to model degradation data, whereas lifetime data are described via the inverse Gaussian distribution. Therefore, the joint maximum likelihood(ML) function can be obtained by combining lifetime and degradation data. Expert knowledge is used according to the maximum entropy method to determine the prior distributions of parameters, thereby making this work different from existing studies that use non-informative prior. The discussion and analysis of different types of expert knowledge also distinguish our research from others. Expert knowledge can be classified into three categories according to practical engineering.Methods for determining prior distribution by using the aforementioned three types of data are presented. The Markov chain Monte Carlo is applied to obtain samples of the parameters and to estimate the residual life of products due to the complexity of the joint ML function and the posterior distribution of parameters. Finally, a numerical example is presented. The effectiveness and practicability of the proposed method are validated by comparing it with residual life estimation that uses non-informative prior.Then, its accuracy and correctness are proven via simulation experiments.

Effects on Genome Constitution and Novel Cell Wall Formation Caused by the Addition of 5RS Rye Chromosome to Common Wheat

The cytological instability of common wheat-rye addition lines was investigated in the present study. The chromosome numbers of almost all addition lines were considerably stable, but those of CS ＋ 5R were very variable. The rye chromosome added in this line was found to be much shorter than expected. Fluorescent in situ hybridization with 5S rDNA and the centromere-speciflc probes clearly revealed that the short rye chromosome contains only a short arm of chromosome 5R （5RS）. In this line, chromosome numbers of both 5RS and common wheat were changeable. The chromosome numbers ranged from 2n = 36 to 2n = 44 in the cells carrying two 5RS, and ranged from 2n = 31 to 2n = 44 in one 5RS cells. In addition to the chromosome instability, the muIticells wrapped in a sac-like structure were frequently observed in the root meristematic tissues of CS ＋5RS after the enzyme treatment for chromosome preparation. Genomic in situ hybridization with rye DNA as a probe showed that all cells in sacs investigated were at the interphase stage and contained one or two 5RS chromosomes. An electron microscopic analysis revealed that the cells of CS＋5RS, particularly in sacs, have abnormal （irregular and curved） cell walls. These results indicate that 5RS has （a） specific factor（s） influencing the cell wall development as well as the genome stability.