TORC1(target of rapamycin complex 1)可整合营养、能量、生长因子及氨基酸等多种细胞外信号,调控基因转录、蛋白质翻译、核糖体合成等生物过程,在细胞生长和凋亡中发挥极为重要的作用。亮氨酰-tRNA合成酶(LeuRS)的经典功能是催化合成...TORC1(target of rapamycin complex 1)可整合营养、能量、生长因子及氨基酸等多种细胞外信号,调控基因转录、蛋白质翻译、核糖体合成等生物过程,在细胞生长和凋亡中发挥极为重要的作用。亮氨酰-tRNA合成酶(LeuRS)的经典功能是催化合成亮氨酰-tRNA直接参与遗传信息的解码合成蛋白质。最新研究结果表明人细胞质LeuRS除了经典功能外,还参与调控TORC1途径。综述了LeuRS的非经典功能,它是如何通过感受细胞内的亮氨酸浓度来调节TORC1活性的。这些结果表明了古老的氨基酰-tRNA合成酶家族在进化的过程中被赋予了新的功能。展开更多
酿酒酵母的TORC1(target of rapamycin complex 1)复合体是由Kog1、Lst8、Tco89以及Tor1或者Tor2组成,其中,Tor1和Tor2最初是作为雷帕霉素作用靶点而在1991年被发现的。近年来的一些研究表明,TORC1以及另一个相似的复合体TORC2参与营养...酿酒酵母的TORC1(target of rapamycin complex 1)复合体是由Kog1、Lst8、Tco89以及Tor1或者Tor2组成,其中,Tor1和Tor2最初是作为雷帕霉素作用靶点而在1991年被发现的。近年来的一些研究表明,TORC1以及另一个相似的复合体TORC2参与营养代谢、核糖体合成、细胞周期、自噬衰老等细胞进程。近几年来对TORC1上游调控元件EGO(escape from rapamycin-induced growth arrest)复合体的深入研究,很大程度上解释了TORC1对氨基酸的感知途径。核糖体的生物合成是高度耗能的过程,而TORC1在r RNA转录及核糖体蛋白合成的过程中起到重要的控制作用。该文以酿酒酵母TORC1为例,回顾它的发现过程,并综述近几年在TORC1上游调控元件以及核糖体合成中作用的研究进展。展开更多
AIM: To investigate the molecular mechanisms of berberine inhibition of hepatic gluconeogenesis in a diabetic rat model.METHODS: The 40 rats were randomly divided into five groups. One group was selected as the normal...AIM: To investigate the molecular mechanisms of berberine inhibition of hepatic gluconeogenesis in a diabetic rat model.METHODS: The 40 rats were randomly divided into five groups. One group was selected as the normal group. In the remaining groups(n = 8 each), the rats were fed on a high-fat diet for 1 mo and received intravenous injection of streptozotocin for induction of the diabetic models. Berberine(156 mg/kg per day)(berberine group) or metformin(184 mg/kg per day)(metformin group) was intragastrically administered to the diabetic rats and 5-aminoimidazole-4-carboxamide1-β-D-ribofuranoside(AICAR)(0.5 mg/kg per day)(AICAR group) was subcutaneously injected to the diabetic rats for 12 wk. The remaining eight diabetic rats served as the model group. Fasting plasma glucose and insulin levels as well as lipid profile were tested.The expressions of proteins were examined by western blotting. The nuclear translocation of CREB-regulated transcription co-activator(TORC)2 was observed by immunohistochemical staining. RESULTS: Berberine improved impaired glucose tolerance and decreased plasma hyperlipidemia. Moreover, berberine decreased fasting plasma insulin and homeostasis model assessment of insulin resistance(HOMA-IR). Berberine upregulated protein expression of liver kinase(LK)B1, AMP-activated protein kinase(AMPK) and phosphorylated AMPK(p-AMPK). The level of phophorylated TORC2(p-TORC2) protein in the cytoplasm was higher in the berberine group than in the model group, and no significant difference in total TORC2 protein level was observed. Immunohistochemical staining revealed that more TORC2 was localized in the cytoplasm of the berberine group than in the model group. Moreover, berberine treatment downregulated protein expression of the key gluconeogenic enzymes(phosphoenolpyruvate carboxykinase and glucose-6-phosphatase) in the liver tissues. CONCLUSION: Our findings revealed that berberine inhibited hepatic gluconeogenesis via the regulation of the LKB1-AMPK-TORC2 signaling pathway.展开更多
Background： To investigate the effects of dietary crude protein（CP） restriction on muscle fiber characteristics and key regulators related to protein deposition in skeletal muscle, a total of 18 growing-finishing p...Background： To investigate the effects of dietary crude protein（CP） restriction on muscle fiber characteristics and key regulators related to protein deposition in skeletal muscle, a total of 18 growing-finishing pigs（62.30 ± 0.88 kg）were allotted to 3 groups and fed with the recommended adequate protein（AP, 16 % CP） diet, moderately restricted protein（MP, 13 % CP） diet and low protein（LP, 10 % CP） diet, respectively. The skeletal muscle of different locations in pigs, including longissimus dorsi muscle（LDM）, psoas major muscle（PMM） and biceps femoris muscle（BFM） were collected and analyzed.Results： Results showed that growing-finishing pigs fed the MP or AP diet improved（P 〈 0.01） the average daily gain and feed： gain ratio compared with those fed the LP diet, and the MP diet tended to increase（P = 0.09） the weight of LDM. Moreover, the ATP content and energy charge value were varied among muscle samples from different locations of pigs fed the reduced protein diets. We also observed that pigs fed the MP diet up-regulated（P 〈 0.05） muscular m RNA expression of all the selected key genes, except that myosin heavy chain（My HC） IIb,My HC IIx, while m RNA expression of ubiquitin ligases genes was not affected by dietary CP level. Additionally, the activation of mammalian target of rapamycin complex 1（m TORC1） pathway was stimulated（P 〈 0.05） in skeletal muscle of the pigs fed the MP or AP diet compared with those fed the LP diet.Conclusion： The results suggest that the pigs fed the MP diet could catch up to the growth performance and the LDM weight of the pigs fed the AP diet, and the underlying mechanism may be partly due to the alteration in energy status, modulation of muscle fiber characteristics and m TORC1 activation as well as its downstream effectors in skeletal muscle of different locations in growing-finishing pigs.展开更多
无人驾驶技术的关键是决策层根据感知环节输入信息做出准确指令。强化学习和模仿学习比传统规则更适用于复杂场景。但以行为克隆为代表的模仿学习存在复合误差问题,使用优先经验回放算法对行为克隆进行改进,提升模型对演示数据集的拟合...无人驾驶技术的关键是决策层根据感知环节输入信息做出准确指令。强化学习和模仿学习比传统规则更适用于复杂场景。但以行为克隆为代表的模仿学习存在复合误差问题,使用优先经验回放算法对行为克隆进行改进,提升模型对演示数据集的拟合能力;原DDPG(deep deterministic policy gradient)算法存在探索效率低下问题,使用经验池分离以及随机网络蒸馏技术(random network distillation,RND)对DDPG算法进行改进,提升DDPG算法训练效率。使用改进后的算法进行联合训练,减少DDPG训练前期的无用探索。通过TORCS(the open racing car simulator)仿真平台验证,实验结果表明该方法在相同的训练次数内,能够探索出更稳定的道路保持、速度保持和避障能力。展开更多
深度确定性策略梯度(deep deterministic policy gradient,DDPG)算法在自动驾驶领域中应用广泛,但DDPG算法因采用均匀采样而导致低效率策略比例较高、训练效率低、收敛速度慢等.提出了基于优先级的深度确定性策略梯度(priority-based DD...深度确定性策略梯度(deep deterministic policy gradient,DDPG)算法在自动驾驶领域中应用广泛,但DDPG算法因采用均匀采样而导致低效率策略比例较高、训练效率低、收敛速度慢等.提出了基于优先级的深度确定性策略梯度(priority-based DDPD,P-DDPG)算法,通过优先级采样代替均匀采样来提升采样利用率、改善探索策略和提高神经网络训练效率,并且提出新的奖励函数作为评价标准.最后,在开源赛车模拟(The Open Racing Car Simulator,TORCS)平台上对P-DDPG算法的性能进行了测试,结果表明相对于DDPG算法,P-DDPG算法的累积奖励在25回合之后就有明显提升而DDPG在100回合之后训练效果才逐渐显现,提升约4倍.P-DDPG算法不仅训练效率提升且收敛速度加快.展开更多
文摘TORC1(target of rapamycin complex 1)可整合营养、能量、生长因子及氨基酸等多种细胞外信号,调控基因转录、蛋白质翻译、核糖体合成等生物过程,在细胞生长和凋亡中发挥极为重要的作用。亮氨酰-tRNA合成酶(LeuRS)的经典功能是催化合成亮氨酰-tRNA直接参与遗传信息的解码合成蛋白质。最新研究结果表明人细胞质LeuRS除了经典功能外,还参与调控TORC1途径。综述了LeuRS的非经典功能,它是如何通过感受细胞内的亮氨酸浓度来调节TORC1活性的。这些结果表明了古老的氨基酰-tRNA合成酶家族在进化的过程中被赋予了新的功能。
文摘酿酒酵母的TORC1(target of rapamycin complex 1)复合体是由Kog1、Lst8、Tco89以及Tor1或者Tor2组成,其中,Tor1和Tor2最初是作为雷帕霉素作用靶点而在1991年被发现的。近年来的一些研究表明,TORC1以及另一个相似的复合体TORC2参与营养代谢、核糖体合成、细胞周期、自噬衰老等细胞进程。近几年来对TORC1上游调控元件EGO(escape from rapamycin-induced growth arrest)复合体的深入研究,很大程度上解释了TORC1对氨基酸的感知途径。核糖体的生物合成是高度耗能的过程,而TORC1在r RNA转录及核糖体蛋白合成的过程中起到重要的控制作用。该文以酿酒酵母TORC1为例,回顾它的发现过程,并综述近几年在TORC1上游调控元件以及核糖体合成中作用的研究进展。
基金Supported by National Natural Science Foundation of China,No.30973836
文摘AIM: To investigate the molecular mechanisms of berberine inhibition of hepatic gluconeogenesis in a diabetic rat model.METHODS: The 40 rats were randomly divided into five groups. One group was selected as the normal group. In the remaining groups(n = 8 each), the rats were fed on a high-fat diet for 1 mo and received intravenous injection of streptozotocin for induction of the diabetic models. Berberine(156 mg/kg per day)(berberine group) or metformin(184 mg/kg per day)(metformin group) was intragastrically administered to the diabetic rats and 5-aminoimidazole-4-carboxamide1-β-D-ribofuranoside(AICAR)(0.5 mg/kg per day)(AICAR group) was subcutaneously injected to the diabetic rats for 12 wk. The remaining eight diabetic rats served as the model group. Fasting plasma glucose and insulin levels as well as lipid profile were tested.The expressions of proteins were examined by western blotting. The nuclear translocation of CREB-regulated transcription co-activator(TORC)2 was observed by immunohistochemical staining. RESULTS: Berberine improved impaired glucose tolerance and decreased plasma hyperlipidemia. Moreover, berberine decreased fasting plasma insulin and homeostasis model assessment of insulin resistance(HOMA-IR). Berberine upregulated protein expression of liver kinase(LK)B1, AMP-activated protein kinase(AMPK) and phosphorylated AMPK(p-AMPK). The level of phophorylated TORC2(p-TORC2) protein in the cytoplasm was higher in the berberine group than in the model group, and no significant difference in total TORC2 protein level was observed. Immunohistochemical staining revealed that more TORC2 was localized in the cytoplasm of the berberine group than in the model group. Moreover, berberine treatment downregulated protein expression of the key gluconeogenic enzymes(phosphoenolpyruvate carboxykinase and glucose-6-phosphatase) in the liver tissues. CONCLUSION: Our findings revealed that berberine inhibited hepatic gluconeogenesis via the regulation of the LKB1-AMPK-TORC2 signaling pathway.
基金financially supported by the National Basic Research Program of China(2013CB127305)the Nature Science Foundation of Hunan Province(S2014J504I)+1 种基金the Major Project of Hunan Province(2015NK1002)the National Science and Technology Ministry(2014BAD08B11)
文摘Background： To investigate the effects of dietary crude protein（CP） restriction on muscle fiber characteristics and key regulators related to protein deposition in skeletal muscle, a total of 18 growing-finishing pigs（62.30 ± 0.88 kg）were allotted to 3 groups and fed with the recommended adequate protein（AP, 16 % CP） diet, moderately restricted protein（MP, 13 % CP） diet and low protein（LP, 10 % CP） diet, respectively. The skeletal muscle of different locations in pigs, including longissimus dorsi muscle（LDM）, psoas major muscle（PMM） and biceps femoris muscle（BFM） were collected and analyzed.Results： Results showed that growing-finishing pigs fed the MP or AP diet improved（P 〈 0.01） the average daily gain and feed： gain ratio compared with those fed the LP diet, and the MP diet tended to increase（P = 0.09） the weight of LDM. Moreover, the ATP content and energy charge value were varied among muscle samples from different locations of pigs fed the reduced protein diets. We also observed that pigs fed the MP diet up-regulated（P 〈 0.05） muscular m RNA expression of all the selected key genes, except that myosin heavy chain（My HC） IIb,My HC IIx, while m RNA expression of ubiquitin ligases genes was not affected by dietary CP level. Additionally, the activation of mammalian target of rapamycin complex 1（m TORC1） pathway was stimulated（P 〈 0.05） in skeletal muscle of the pigs fed the MP or AP diet compared with those fed the LP diet.Conclusion： The results suggest that the pigs fed the MP diet could catch up to the growth performance and the LDM weight of the pigs fed the AP diet, and the underlying mechanism may be partly due to the alteration in energy status, modulation of muscle fiber characteristics and m TORC1 activation as well as its downstream effectors in skeletal muscle of different locations in growing-finishing pigs.
文摘无人驾驶技术的关键是决策层根据感知环节输入信息做出准确指令。强化学习和模仿学习比传统规则更适用于复杂场景。但以行为克隆为代表的模仿学习存在复合误差问题,使用优先经验回放算法对行为克隆进行改进,提升模型对演示数据集的拟合能力;原DDPG(deep deterministic policy gradient)算法存在探索效率低下问题,使用经验池分离以及随机网络蒸馏技术(random network distillation,RND)对DDPG算法进行改进,提升DDPG算法训练效率。使用改进后的算法进行联合训练,减少DDPG训练前期的无用探索。通过TORCS(the open racing car simulator)仿真平台验证,实验结果表明该方法在相同的训练次数内,能够探索出更稳定的道路保持、速度保持和避障能力。
文摘深度确定性策略梯度(deep deterministic policy gradient,DDPG)算法在自动驾驶领域中应用广泛,但DDPG算法因采用均匀采样而导致低效率策略比例较高、训练效率低、收敛速度慢等.提出了基于优先级的深度确定性策略梯度(priority-based DDPD,P-DDPG)算法,通过优先级采样代替均匀采样来提升采样利用率、改善探索策略和提高神经网络训练效率,并且提出新的奖励函数作为评价标准.最后,在开源赛车模拟(The Open Racing Car Simulator,TORCS)平台上对P-DDPG算法的性能进行了测试,结果表明相对于DDPG算法,P-DDPG算法的累积奖励在25回合之后就有明显提升而DDPG在100回合之后训练效果才逐渐显现,提升约4倍.P-DDPG算法不仅训练效率提升且收敛速度加快.
