The Molecular Mechanism and Biological Function of the Regulation of p53 Activity by Axin Complex

细胞在受到基因毒素的胁迫下会选择进入细胞周期阻滞以修复受损的遗传信息，或是进入凋亡途径以从群体中剔除这些带有错误信息的危险分子。人们普遍认为这两种细胞命运是由以p53为核心的信号传导途径决定的。然而，对于p53被激活的阈值是如何由繁多的因子精细地协作调节的问题，人们还一直没有明确答案。本文展示了Axin这个Wnt信号通路的核心调控分子，在这两种不同的细胞行为中，和Pirh2，Tip60，HIPK2以及p53形成不同的复合体。在亚致死剂量的紫外辐射或是柔红霉素的处理下，Pirh2通过竞争HIPK2与Axin的结合而阻碍Axin介导的由HIPK2催化的p53的46位氨基酸的磷酸化。而在致死剂量的刺...Cells can undergo cell-cycle arrest to repair damaged DNA or apoptosis to eliminate permanently damaged cells that carry inaccurate genetic information following genotoxic stresses. The two cell fates are determined by signaling cascades that seem to converge on p53 signaling. However, how thresholds of p53 activation are intricately controlled by orchestration of increasingly many factors remains...学位：理学博士院系专业：生命科学学院生物医学科学系_生物化学与分子生物学学号：2012005140332

Electrochemical property of spinel LiMn_2O_4 prepared by sol-gel method

利用循环伏安法 (CV )、恒流充放电、电化学阻抗谱 (EIS)等电化学手段研究了溶胶凝胶法制备的尖晶石型LiMn2 O4 的电化学性质。结果表明用溶胶凝胶法制备的样品放电容量大 ,可逆性好 ,其中 5 5 0℃煅烧的样品电化学性能最好 ;XRD结果表明 ,样品经过充放电 ,尖晶石结构仍保留 ,但出现深度放电产物Li2 Mn2 O4 。The electrochemical properties of spinel LiMn 2O 4 electrodes prepared by a sol gel method were studied by cyclic voltammetry, constant current charge discharge and electrochemical impedance spectrum(EIS) techniques. The experimental results showed that the electrochemical performance of the samples prepared by sol gel method was better than that of the sample prepared by normal method. The electrochemical performance of the sample prepared by sol gel method at 550℃ showed the best electrochemical performance. After constant current charge discharge the spinel structures in all samples were reserved and deeply discharging product Li 2Mn 2O 4 was detected from XRD results.国家自然科学基金 ( 2 98330 90 );; “86 3”高技术发展计划 ( 715 -0 0 4-0 2 5 0

Investigation of lithium manganese oxides with large tunnel structure as electrode material in Li ion batteries

锂锰氧化物材料是一类重要的锂离子电池电极材料。文中报道一种新型大隧道结构镁锰复合氧化物〔结构类型：钡镁锰矿（TOdOrOkITE）型〕的合成方法及其电化学性能表征。X-光衍射（Xrd）谱证实了合成物具有所预想的（3x3）隧道结构。在慢速循环伏安图中可发现该类电极材料分别在3.35V及2.45V（VS.lI）出现一对锂离子的脱出-嵌入峰。充放电实验结果表明：该类大隧道结构复合氧化物可作为一种3V锂离子电池的电极材料，当充放电电流密度为0.1MA/CM2时，材料的初次容量可达158MAg/H，经过4次充放电循环后其容量仍可保持在约130MAH/g。Lithium manganese oxide is one kind of the important electrode material of Li ion batteries.In this paper, investigations of a novel Li Mn oxide electrode material with large tunnel structure such as todorokite type electode material For Li ion batteries are carried out in the lab.It is demonstrated that the material synthesized has a todo rokite structure (i.e.3×3 tunnel)using X ray diFFraction(XRD) method.It is also observed that a couple of deintercalation/intercalation peaks of lithium ion appear at 3.35V and 2.46V (vs.Li) respectively in the slow rate cyclic voltammograms.In addition,it is Found that the material shows quite good cyclic perFormance,the initial capacity of the material is 158mAh/g,and its discharge capacity is still kept at about 130mAh/g aFter Four cycles at charging/discharging current density of 0.1mA/cm 2.福建省自然科学基金;杰出青年基

MySQL密码认证算法的FPGA优化实现

My SQL数据库软件被广泛地应用于WEB项目中,因此它的安全性极为重要。本文针对My SQL密码认证算法的FPGA实现以及应用进行研究,利用并行化、流水线架构实现My SQL认证算法。提出一种基于BRAM的SHA-1算法流水线架构并对其流水线级数进行优化,从而实现高性能。同时利用多模块并行,多密码验证算法,以提高硬件运行速度和计算资源的利用效率。通过优化,高性能实现了基于FPGA硬件的My SQL认证算法,单块芯片的口令恢复速度为18亿个口令密码每秒,多个FPGA构成子板的认证速度为72亿/秒,比采用GPU GTX 690平台的速度提高了5倍。本研究项目获得集成电路设计与测试分析福建省高校重点实验室建设资金.厦门市科技局科技专项经费以及2017年厦门大学教学改革研究项目资金的支持

Novel cathode material for lithium ion batteries Investigation of the intercalation behavior of manganese dioxide nano fiber

采用TEM、Xrd分析等方法对新型二氧化锰纳米纤维电极材料进行表征，TEM观测结果显示这种锰材料是由许多二氧化锰纳米纤维缠绕成巢状，其纤维直径约为1nM~10nM之间；从Xrd分析表明，它是一种复合结构的锰氧化物，以钡镁锰矿为主体结构，并含有其他钠水锰矿及水羟锰矿结构。从样品电极在1MOl/llIClO4的PC-dME（1∶1）溶剂中的循环伏安曲线，可以看出在扫描的电压范围内，在3.8V和2.8V附近出现一对可逆对称的氧化还原峰，它对应于二氧化锰纳米纤维电极中锂离子的脱出-嵌入反应。通过二氧化锰纳米纤维电极在不同电流密度下的放电，可以看出该电极采用小电流放电（0.24MA/CM2），其容量可达到约190MAH/g，而且具有3V的放电平台；而在较大的电流密度（0.96MA/CM2）放电仍具有约150MAH/g的放电容量。可见，该电极具有良好的负荷特性和较高的放电容量。A novel cathode material (MnO 2) has been characterized by using transmission electron microscope (TEM) and X ray diffraction (XRD). From the TEM examination, it was found that the MnO 2 has a distinct birds nest shaped nano fiber with the diameter in the range of 1nm～10 nm. XRD data shows that the MnO 2 has a complex structure that is in the form of todorokite (3×3 tunnel) birnessite, and vernadite structure. Cyclic voltammetry has been performed in 1 mol/L LiClO 4的PC DME(1∶1) electrolyte solution. It can be seen that a pair of reversible redox peaks, which mainly occurs in the potential ranged from 2.8 to 3.8 V vs.Li/Li +, it can be described by a lithium intercalation mechanism. The galvanostatic charge discharge experiments at various current density reveal that the MnO 2 nano fiber electrodes have a high electrochemical performance and stability. The reversible capacity can reach 190 mAh/g, 150 mAh/g at lower and higher current density respectively, i.e. 0.24mA/cm 2 and 0.96mA/cm 2.国家“863”高技术发展计划课题;中国大洋矿产资源研究开发课题;国家自然科学基

AIDA通过内质网相关的蛋白质降解途径选择性下调脂肪合成途径的代谢酶从而减缓肠道脂肪吸收并防止肥胖发生

文章简介肠道对膳食脂肪吸收的效率是个人是否易患肥胖的主要决定因素之一。然而,目前人们还不清楚脂肪吸收是如何受调控并导致肥胖的。本研究表明,抑制内质网相关的蛋白质降解途径会提高甘油三酯合成途径的数个代谢酶的水平,并促进小肠对脂肪的吸收。包含C2结构域的蛋白AIDA作为一个重要国家重点基础研发计划;;\n国家自然科学基金;;\n厦门大学校长基金等支

Protein phosphorylation-acetylation cascade connects growth factor deprivation to autophagy

Different from unicellular organisms, metazoan cells require the presence of extracellular growth factors to utilize environmental nutrients. However, the underlying mechanism was unclear. We have delineated a pathway, in which glycogen synthase kinase 3 (GSK3) in cells deprived of growth factors phosphorylates and activates the acetyltransferase KAT5/TIP60, which in turn stimulates the protein kinase ULK1 to elicit autophagy. Cells with the Kat5/Tip60 gene replaced with Kat5(S86A) that cannot be phosphorylated by GSK3 are resistant to serum starvation-induced autophagy. Acetylation sites on ULK1 were mapped to K162 and K606, and the acetylation-defective mutant ULK1(K162,606R) displays reduced kinase activity and fails to rescue autophagy in Ulk1(-/-) mouse embryonic fibroblasts, indicating that acetylation is vital to the activation of ULK1. The GSK3-KAT5-ULK1 cascade seems to be specific for cells to sense growth factors, as KAT5 phosphorylation is not enhanced under glucose deprivation. Distinct from the glucose starvation-autophagy pathway that is conserved in all eukaryotic organisms, the growth factor deprivation response pathway is perhaps unique to metazoan organisms.973 Program [2011CB910800]; NSFC [31130016, 30921005, 31000621]; Fundamental Research Funds for the Central Universities [2010121094]; MOE of China [B06016

AMP as a Low-Energy Charge Signal Autonomously Initiates Assembly of AXIN-AMPK-LKB1 Complex for AMPK Activation

The AMP-activated protein kinase (AMPK) is a master regulator of metabolic homeostasis by sensing cellular energy status. AMPK is mainly activated via phosphorylation by LKB1 when cellular AMP/ADP levels are increased. However, how AMP/ADP brings about AMPK phosphorylation remains unclear. Here, we show that it is AMP, but not ADP, that drives AXIN to directly tether LKB1 to phosphorylate AMPK. The complex formation of AXIN-AMPK-LKB1 is greatly enhanced in glucose-starved or AICAR-treated cells and in cell-free systems supplemented with exogenous AMP. Depletion of AXIN abrogated starvation-induced AMPK-LKB1 colocalization. Importantly, adenovirus-based knockdown of AXIN in the mouse liver impaired AMPK activation and caused exacerbated fatty liver after starvation, underscoring an essential role of AXIN in AMPK activation. These findings demonstrate an initiating role of AMP and demonstrate that AXIN directly transmits AMP binding of AMPK to its activation by LKB1, uncovering the mechanistic route for AMP to elicit AMPK activation by LKB1.http://news.xmu.edu.cn/s/13/t/542/22/a9/info139945.ht

AIDA directly connects sympathetic innervation to adaptive thermogenesis by UCP1

AIDA最早是由林圣彩教授团队首先鉴定和命名的。2007年林圣彩教授团队与孟安明院士团队合作发现AIDA在斑马鱼体轴发育中的功能(Rui, 2007)。2018年，林圣彩教授团队首次发现了AIDA在哺乳动物中的功能，即AIDA介导的内质网降解途径通过降解脂肪合成途径中的关键酶，而限制膳食脂肪在肠道的吸收这一内在抵御肥胖(Luo, 2018)。而本次成果揭示了AIDA在棕色脂肪组织中特定的功能。这些工作将AIDA引入了脂质应激代谢的重要环节，包括脂质吸收和依赖于脂质的产热过程。该论文的共同第一作者为生命科学学院博士生史猛和硕士生黄晓羽，林圣彩教授和林舒勇教授则为共同通讯作者。【Abstract】The sympathetic nervous system–catecholamine–uncoupling protein 1 (UCP1) axis plays an essential role in non-shivering adaptive thermogenesis. However, whether there exists a direct effector that physically connects catecholamine signalling to UCP1 in response to acute cold is unknown. Here we report that outer mitochondrial membrane-located AIDA is phosphorylated at S161 by the catecholamine-activated protein kinase A (PKA). Phosphorylated AIDA translocates to the intermembrane space, where it binds to and activates the uncoupling activity of UCP1 by promoting cysteine oxidation of UCP1.Adipocyte-specific depletion of AIDA abrogates UCP1-dependent thermogenesis, resulting in hypothermia during acute cold exposure. Re-expression of S161A-AIDA, unlike wild-type AIDA, fails to restore the acute cold response in Aida-knockout mice.The PKA–AIDA–UCP1 axis is highly conserved in mammals, including hibernators. Denervation of the sympathetic postganglionic fibres abolishes cold-induced AIDA-dependent thermogenesis. These findings uncover a direct mechanistic link between sympathetic input and UCP1-mediated adaptive thermogenesis.We thank Y. Li, E. Gnaiger, T. Kuwaki, J. R. B. Lighton, E. T. Chouchani and D. Jiang for technical instruction; X. Li and X.-D. Jiang (Core Facility of Biomedical, Xiamen University) for raising the p-S161-AIDA antibody; the Xiamen University Laboratory Animal Center for the mouse in vitro fertilization service and all the other members of S.C.L. laboratory for their technical assistance. This work was supported by grants from the National Key Research and Development Project of China (grant no. 2016YFA0502001) and the National Natural Science Foundation of China (grant nos 31822027, 31871168, 31690101, 91854208 and 82088102), the Fundamental Research Funds for the Central Universities (grant nos 20720190084 and 20720200069), Project ‘111’ sponsored by the State Bureau of Foreign Experts and Ministry of Education of China (grant no. BP2018017), the Youth Innovation Fund of Xiamen (grant no. 3502Z20206028), the Natural Science Foundation of Fujian Province of China (grant no. 2017J01364) and XMU Training Program of Innovation and Entrepreneurship for Undergraduates (grant no. 2019×0666). 该工作得到了厦门大学实验动物中心和生物医学学部仪器平台的重要协助和国家重点研究和发展项目，国家自然科学基金，厦门大学校长基金等的支持

The Lysosomal v-ATPase-Ragulator Complex Is a Common Activator for AMPK and mTORC1, Acting as a Switch between Catabolism and Anabolism

林圣彩教授课题组长期致力于细胞信号转导的研究。近年来，该课题组潜心研究，不断攻关，取得了一系列重大成果，如揭示细胞如何应对生长因子缺乏的内在机理，发现了细胞自噬“路线图”、还发现了细胞如何感应“饥饿”信号AMP的信号传导通路等。其中，“发现细胞自噬‘路线图’”成果曾登上《科学》杂志，并入选2012年度“中国科学十大进展”。AMPK and mTOR play principal roles in governing metabolic programs; however, mechanisms underlying the coordination of the two inversely regulated kinases remain unclear. In this study we found, most surprisingly, that the late endosomal/lysosomal protein complex v-ATPase-Ragulator, essential for activation of mTORC1, is also required for AMPK activation. We also uncovered that AMPK is a residential protein of late endosome/lysosome. Under glucose starvation, the v-ATPase-Ragulator complex is accessible to AXIN/LKB1 for AMPK activation. Concurrently, the guanine nucleotide exchange factor (GEF) activity of Ragulator toward RAG is inhibited by AXIN, causing dissociation from endosome and inactivation of mTORC1. We have thus revealed that the v-ATPase-Ragulator complex is also an initiating sensor for energy stress and meanwhile serves as an endosomal docking site for LKB1-mediated AMPK activation by forming the v-ATPase-Ragulator-AXIN/LKB1-AMPK complex, thereby providing a switch between catabolism and anabolism. Our current study also emphasizes a general role of late endosome/lysosome in controlling metabolic programs