RPS23RG1 modulates tau phosphorylation and axon outgrowth through regulating p35 proteasomal degradation

Tau蛋白病（Tauopathies）是由过度磷酸化的tau蛋白聚集形成神经纤维缠结为特征的一类神经退行性疾病，包括阿尔茨海默病（Alzheimer’s disease, AD）、进行性核上性麻痹（Progressive superanuclear palsy, PSP）、额颞叶痴呆（Frontotemporal dementia, FTD）等。随着全球社会结构的老龄化，tau蛋白病患者比率迅速增加，给个人和社会带来巨大的经济及精神负担。厦门大学神经科学研究所张云武教授团队最新发现RPS23RG1（RR1）的胞内羧基端区域能够与Cdk5激酶的激活蛋白p35的氨基端相互作用，介导p35的膜定位并影响其泛素化降解，从而调控在tau蛋白异常磷酸化过程中发挥重要作用的Cdk5激酶的活性。团队研究表明RPS23RG1通过其胞内羧基端与p35相互作用，介导p35膜结合和降解，从而抑制Cdk5活性，平衡tau磷酸化水平，促进轴突生长。此外，RPS23RG1的跨膜区与腺苷酸环化酶AC相互作用，抑制GSK3-β活性，同样控制tau过度磷酸化。提示RPS23RG1是改善tau过度磷酸化水平及治疗tau蛋白病的潜在靶点。 厦门大学医学院神经科学研究所博士后赵东栋为该研究第一作者，张云武教授为通讯作者。【Abstract】Tauopathies are a group of neurodegenerative diseases characterized by hyperphosphorylation of the microtubule-binding protein, tau, and typically feature axon impairment and synaptic dysfunction. Cyclin-dependent kinase5 (Cdk5) is a major tau kinase and its activity requires p35 or p25 regulatory subunits. P35 is subjected to rapid proteasomal degradation in its membrane-bound form and is cleaved by calpain under stress to a stable p25 form, leading to aberrant Cdk5 activation and tau hyperphosphorylation. The type Ib transmembrane protein RPS23RG1 has been implicated in Alzheimer’s disease (AD). However, physiological and pathological roles for RPS23RG1 in AD and other tauopathies are largely unclear. Herein, we observed retarded axon outgrowth, elevated p35 and p25 protein levels, and increased tau phosphorylation at major Cdk5 phosphorylation sites in Rps23rg1 knockout (KO) mice. Both downregulation of p35 and the Cdk5 inhibitor roscovitine attenuated tau hyperphosphorylation and axon outgrowth impairment in Rps23rg1 KO neurons. Interestingly, interactions between the RPS23RG1 carboxyl-terminus and p35 amino-terminus promoted p35 membrane distribution and proteasomal degradation. Moreover, P301L tau transgenic (Tg) mice showed increased tau hyperphosphorylation with reduced RPS23RG1 levels and impaired axon outgrowth. Overexpression of RPS23RG1 markedly attenuated tau hyperphosphorylation and axon outgrowth defects in P301L tau Tg neurons. Our results demonstrate the involvement of RPS23RG1 in tauopathy disorders, and implicate a role for RPS23RG1 in inhibiting tau hyperphosphorylation through homeostatic p35 degradation and suppression of Cdk5 activation. Reduced RPS23RG1 levels in tauopathy trigger aberrant Cdk5-p35 activation, consequent tau hyperphosphorylation, and axon outgrowth impairment, suggesting that RPS23RG1 may be a potential therapeutic target in tauopathy disorders.This work was supported by grants from National Key Research and Development Program of China (2016YFC1305903 and 2018YFC2000400 to Y-wZ), National Natural Science Foundation of China (81771377, U1705285, 91332112, and 81225008 to Y-wZ), Fundamental Research Funds for the Central Universities (20720180049 to Y-wZ), the Fujian Provincial Health Commission-Education Department Joint Tackling Plan (WKJ2016-2-18 to F-rL), and Postdoctoral Science Foundation of China (2020M671948 to DZ)

貌合神离：中英文同款广告的符号和眼动分析

通过一系列中英文同款广告，该研究结合符号和眼动技术，指出相似的表象之下，微妙的细节调整如何折射出中西方读者对媒介内容叙述方式的不同偏好，以及处理群己关系的不同价值取向，从而呈现出“貌合神离”的警民、亲子、师生、夫妻、男女等社会关系。本文系国家自然科学基金项目“东西方不同文化思维方式对广告说服的影响：一个自下而上的脉络建构与验证”（项目编号：71372076）的阶段性研究成果

BREEDING AND FEEDING CHARACTERISTICS OF HIGH-TEMPERATURE-RESISTANT STRAINS OF ISOCHRYSIS GALBANA

Four strains of Isochrysis galbana, named PHY7001PHY7004, were isolated in microscope and tested for their growth characteristics in high temperatures (33°C, 40°C). The cell size and protein content of the strains were determined and the medium of the one with the fastest growth rate (PHY7004) was optimized. In addition, we conducted feeding experiment of Urechis unicinctus seedlings. Results show that the four strains could grow best at 33°C, of which the growth rate of PHY7004 was the biggest. The average diameter of cell size was 5.57.5 mm, the average fresh-weight protein content of the 4 strains was 34.29 mg/L, of which the protein content of PHY7003 was the highest: 41.80 mg/L. The optimum culture conditions for the fast-growing PHY7004 were pH=7 and N/P=14:1; and U. unicinctus seedling of PHY7002 feeding intensity was the highest. This study provides a reference for screening of high-temperature-resistant bait, and a basis for the bait selection of U. unicinctus seedling

天然气水合物样品声纵波特性和温压影响测量

介绍了低温实验室合成天然气水合物声纵波传播速度和衰减的测量，以及不同温度和压力条件对纯甲烷水合物样品纵波传播速度的影响．在0—15℃温度范围内测量了冰、四氢呋喃（tetrahydrofuran，THF）水合物、天然气水合物样品及它们与砂的混合物样品的声纵波速度和声波穿透后的幅度．当冰、THF水合物、天然气水合物的密度分别为898，895和475kg／m3时，纵波速度分别为3574，3428和2439m／s，衰减依次增大．天然气水合物与砂的混合物的纵波速度明显低于冰与砂和THF水合物与砂的混合物样品的速度，它们的声衰减都比较小．实验室合成的天然气水合物密度比较低，当密度为475kg／m3时，纵波速度为2439m／s；经过压实密度增加，纵波速度随之增加，而衰减逐步减小，当密度为890kg／m3时，速度为3259m／s．在温压影响实验中的两个样品均在同样的初始条件下生成，但水的转化率不一样．在9．6～38MPa的压力范围内，随着活塞压力和孔隙压力的增加，甲烷水合物样品纵波速度也随着增加，从3049m／s增加到3337m／s．不同温度下甲烷水合物样品纵波速度随温度的增加而减少，速度从3800m／s降到3546m／s，且在冰点附近变化很大

基于混合式机器学习的光信噪比预测方法

随着网络技术的蓬勃发展，光网络向着超高速大容量的方向发展，光网络结构越来越复杂，导致网络中光信号传输受到各种物理层损伤的影响。在光通信设备中，物理层最重要的参数就是光信噪比（OSNR），其值的大小直接决定了业务能否正常运行，一旦不能满足要求，将会造成传输错误或失败、服务质量降低和传送消耗增加等问题。文章提出一种准确高效的光通信节点OSNR预测方法，将基于解析式的先验知识方法和基于深度学习的后验知识方法结合起来，提出了一种基于混合式机器学习算法的光通信节点OSNR预测方法，用先验知识去降低神经网络的训练代价，提供高准确度的OSNR预测，研究表明，文章所提方法可以在更苛刻的条件下提供高准确度的机器学习模型

大孔树脂吸附与反相色谱纯化恩拉霉素

恩拉霉素作为多肽类抗生素,是一种新型、安全的饲料添加剂。本文建立了一条基于大孔树脂初纯和反相色谱精制的分离纯化工艺。该工艺路线首先使用AB-8大孔树脂在0.012 mol/L盐酸溶液-甲醇(50:50,V/V)缓冲液条件下洗脱实现恩拉霉素初步纯化,再使用制备型C18反相色谱柱在0.05 mol/L 磷酸二氢钠-乙腈(70:30,V/V) (pH 4.5)缓冲液洗脱下实现恩拉霉素a和b的有效分离,a、b两个组分纯度分别达到98.5%和98.0%,a和b两种有效成分的总收率为29.2%。本研究为恩拉霉素a和b两种纯品的制备以及高纯度恩拉霉素产品的生产提供了参考