Caveolin-1 Is Involved in Radiation-induced ERBB2 Nuclear Transport in Breast Cancer Cells

This study examined the radiation-induced ERBB2 nuclear transport in the BT474 breast cancer cell line and the relationship between caveolin-1 and radiation-induced ERBB2 nuclear transport. The BT474 cells were treated with herceptin (200 nmol/L), PP2 (a caveolin-1 inhibitor, 100 nmol/L) and irradiation combined or alone. Confocal microscopy was used to observe the nuclear import of ERBB2 and caveolin-1 after irradiation. Western blotting was employed to detect the expression of ERBB2, caveolin-1 and DNA-PKcs after irradiation, and immunoprecipitation to identify the ERBB2 and caveolin-1 complex before perinuclear ERBB2 localization. Confocal microscopy showed the transport of ERBB2 and caveolin-1 from the cell membrane to the nucleus 15 min after irradiation and the proteins accumulated at the perinuclear region within 45 min. Western blotting revealed that the expression levels of ERBB2, caveolin-1 and DNA-PKcs were increased after irradiation and reached a peak 45 min later. Both herceptin and PP2 treatments were found to decrease ERBB2 expression. An immune complex composed of ERBB2 and caveolin-1 was found in the herceptin group after irradiation. It was concluded that after irradiation, ERBB2 may be transported from the cell membrane to the nucleus and activate DNA-PKcs to trigger DNA double-strand break (DSB) repair; caveolin-1 may participate in this process. Treatments involving the downregulation of caveolin-1 may increase the radio-sensitization of breast cancer cells.

Using Nuclear Transport Theory to Study Nonlinear Effects Between the Different Strands in DNA

A dynamic model of DNA molecules which takes into account the interaction of the nearestbase pairs between the different strands is presented.The nonlinear effect and phase transition aresimulated by the nuclear transport theory and the method of fractorial moment in high energy physics,re-spectively.The results show that the nonlinear interaction of the nearest base pairs between the differentstrands may play a rule in DNA molecules.

Presence of a long nuclear-localization signal sequence in homeodomain transcription factor Nkx 1.2

Homeodomains,a 60-amino acid sequence encoded by 180 nucleotides,are highly conserved DNA-binding motifs that are present in a variety of transcription factors in species ranging from yeast to humans.The NKX proteins belong to the homeodomain(HD)-containing transcription factor family.They play vital roles in the regulation of morphogenesis.NKX1-2 is one member of the NKX subfamily.At present,information about its nuclear localization signal(NLS)sequence is limited.We studied the NLS sequence of zebrafish Nkx1.2 by introducing sequence changes such as deletion,mutation,and truncation,and identified an NLS motif(QNRRTKWKKQ)that is localized at the C-terminus of the homeodomain.Moreover,the deletion of two amino acid residues(RR)in this NLS motif prevents Nkx1.2 from entering the nucleus,indicating that the two amino acids are essential for Nkx1.2 nuclear localization.However,the NLS motif alone is unable to target cytoplasmic protein glutathione S-transferase(GST)to the nucleus.An intact homeodomain is necessary for mediating the complete nuclear transport of cytoplasmic protein.Unlike most nuclear import proteins with short NLS sequences,a long NLS is present in zebrafish Nkx1.2.We also demonstrated that the sequences of homeodomain of NKX1.2 are well conserved among different species.This study is informative to verify the function of the NKX1.2 protein.

Vesicular glutamate transporter-immunoreactivities in the vestibular nuclear complex of rat

Objective Aims to delineate the distribution profile of three isoforms of vesicular glutamate transporter （VGluT）, viz. VGluT1-3, and their cellular localization within vestibular nuclear complex （VNC）. Methods Brain sections from normal Sprague-Dawley rats were processed immunohistochemically for VGluT detection, employing avidinbiotinylated peroxidase complex method with 3-3＇-diaminobenzidine （DAB） as chromogen. Results The whole VNC expressed all of the three transporters that were observed to be localized to the fiber endings. Compared with VGluT1 and VGluT3, VGluT2 demonstrated a relatively homogeneous distribution, with much higher density in VNC. VGluT3 displayed the highest density in lateral vestibular nucleus and group X, contrasting with the sparse immunostained puncta within vestibular medial and inferior nuclei. Conclusion Glutamtatergic pathways participate in the processing of vestibular signals within VNC mainly through the re-uptake of glutamate into synaptic vesicles by VGluT1 and 2, whereas VGluT3 may play a similar role mainly in areas other than medial and inferior nuclei of VNC.

Phosphatidylglycerol-containing ER-transport vesicles built and restore outer mitochondrial membrane and deliver nuclear DNA translation products to generate cardiolipin in the inner mitochondrial membrane

Phosphatidylglycerol (PG) an important membrane phospholipid required for the synthesis of diphos-phatidylglycerol (DPG) commonly known as cardiolipin (CL) was identified in the fraction of endo-plasmic reticulum (ER)-derived transport vesicles which had no affinity for Golgi. The vesicles were produced in the presence of Brefeldin A (BFA), the agent known to inhibit ER-Golgi transport, and found to display affinity to mitochondria. The analysis revealed that their cargo was not containing proteins that are transported to Golgi, and that their membrane was free of phosphatidylinositol (PI) and ceramides (Cer). The incubation of PG-containing transport vesicles with mitochondria afforded incorporation of their membrane into the Outer Mito-chondrial Membrane (OMM) and formation of lyso-phosphatidylglycerol (LPG). In turn, upon further incubation with fresh transport active cytosol, the mitochondrial LPG was converted to PG. The results of analysis of the OMM, Inner Mitochondrial Mem-brane (IMM) and Inner Mitochondrial Space Components (IMSC) strongly suggest that PG-containing transport vesicles deliver nuclear DNA translation products to the IMSC and thus facilitate CL synthesis in the IMM. In summary, our studies provide evidence that ER-generated PG-enriched transport vesicles represent the general pathway for restitution of mitochondrial membranes and the delivery of nuclear DNA translation products that generate CL, and thus sustain the mitochondrial matrix CL-dependent metabolic reactions.

国际可移动小型堆开发与运输安全研究现状

可移动小型堆(TNPPS)作为小型模块化反应堆(SMR)的一种(一般指30 MW以下的SMR),当通过陆路、海运等方式运输后在运输工具上或者从运输工具卸载后能够运行和产生电能,可以满足偏远、局部区域的供热、用电需求,引起了各国的重视。本文简要介绍了国际可移动小型堆发展现状,重点对国际上不同类型可移动小型堆的特点、可移动小型堆发展面临的问题和挑战进行总结,并重点讨论了可移动小型堆运输安全相关问题及对策建议。

多药耐药相关蛋白转运体在药物性肝损伤中的作用研究进展

肝脏是人体新陈代谢最旺盛的器官,也是体内多种药物的解毒器官。当长期或过量使用药物时会增加药物性肝损伤(DILI)的风险。多药耐药相关蛋白(MRPs)是位于细胞膜上的功能蛋白,可转运多种药物,在DILI中发挥重要作用。MRPs功能的抑制、缺失是药物肝毒性产生的重要原因。本文对MRPs的结构、表达部位及功能进行归纳,并对MRPs与DILI的关系及其改善DILI的机制进行总结,期望更好地了解MRPs转运体与DILI的关系,为后续防治DILI提供参考。

Hepatic drug transporters and nuclear receptors:Regulation by therapeutic agents

The canalicular membrane represents the excretory pole of hepatocytes.Bile is an important route of elimination of potentially toxic endo-and xenobiotics(including drugs and toxins),mediated by the major canalicular transporters:multidrug resistance protein 1(MDR1, ABCB1),also known as P-glycoprotein,multidrug resistance-associated protein 2(MRP2,ABCC2),and the breast cancer resistance protein(BCRP,ABCG2).Their activities depend on regulation of expression and proper localization at the canalicular membrane,as regulated by transcriptional and post-transcriptional events,respectively.At transcriptional level,specific nuclear receptors(NR)s modulated by ligands,co-activators and co-repressors,mediate the physiological requirements of these transporters.This complex system is also responsible for alterations occurring in specific liver pathologies.We briefly describe the major ClassⅡNRs, pregnane X receptor(PXR)and constitutive androstane receptor(CAR),and their role in regulating expression of multidrug resistance proteins.Several therapeutic agents regulate the expression of relevant drug transporters through activation/inactivation of these NRs.We provide some representative examples of the action of therapeutic agents modulating liver drug transporters, which in addition,involve CAR or PXR as mediators.

核电新燃料运输容器聚氨酯泡沫填充材料寿命预测

核电新燃料运输容器长期服役寿命主要受限于填充在壳体中起防震和隔热作用且不可更换的硬质聚氨酯泡沫材料。为评估填充在新燃料运输容器中的硬质聚氨酯泡沫材料的老化寿命,分别在不同温度条件下对硬质聚氨酯泡沫材料进行加速热氧老化试验,定期监测其压缩性能、颜色及微观形貌变化规律,分析其热氧老化行为。根据聚氨酯泡沫材料在不同温度下的压缩强度变化规律,获得聚氨酯泡沫材料在不同温度条件下的老化失效时间,采用阿伦尼乌斯方程外推法预测其在实际服役温度条件下的老化寿命。结果表明,聚氨酯泡沫材料适宜的热氧老化试验温度区间为100~120℃。经微观形貌观察,新燃料运输容器聚氨酯泡沫填充材料在热氧老化试验期间发生泡孔塌陷和泡孔壁破裂的现象,导致压缩强度下降。通过计算分析,在新燃料运输容器设计最高使用温度38℃条件下,预测聚氨酯泡沫材料服役寿命为54 a,能够满足30 a的设计要求。

基于空间核反应堆事故工况下的仿真研究

随着我国航天事业的发展,空间核反应堆电源因其功率密度大、寿命长、环境适应性强、工作性能稳定等特点,已成为未来空间探索的理想动力能源。为了研究空间核反应堆在正常运行工况和掉落事故工况下的安全性,基于中子输运计算程序Open MC对空间核反应堆开展临界仿真研究,得到正常工况下堆芯反应性、控制鼓价值以及燃耗计算等一系列重要参数。同时模拟分析了空间核反应堆在水淹和沙埋2种事故工况下的堆芯反应性和中子能谱。结果表明,空间核反应堆在保持控制鼓功能正常的掉落事故工况下仍然有3000pcm左右的负反应性以防止反应堆达到临界状态,保证了空间核反应堆在此事故工况下的安全性,表明此堆芯的设计是安全可靠的。空间核反应堆仿真研究对我国未来空间核反应堆实际应用具有一定的指导意义。计算结果为空间核反应堆的安全分析和事故分析提供了重要的参考数据。

我国空间推进技术领域发展思考与建议

我国空间推进技术领域历经60余年发展形成了较完善的技术体系和较丰富的产品谱系,支持了载人航天、应用卫星、深空探测等重大工程应用;面向我国航天领域未来规划、重大工程和科学项目的应用需求,空间推进系统现有的技术水平存在不足,亟需谋划创新发展和突破方向。本文从电推进、化学推进、核推进、新概念空间推进等角度出发,系统梳理了空间推进系统的发展现状;重点提炼了高性能、低成本的空间推进系统支撑低轨小卫星组网发展,大推力、可重复使用的低温化学推进技术推动新型空间运输系统发展,多类型、长寿命的空间推进技术保障深空关键应用等未来应用需求。研究认为,我国空间推进技术领域面临系统可靠性和寿命亟需进一步提高、部分领域的产品成熟度与国际先进水平差距明显、产品成本高、可选推进技术种类少且重点技术研究滞后等迫切挑战,需开展顶层规划、优化技术选择,重视基础研究、构建发展机制,在重点技术方向上分类推进科研攻关,尽快实现低轨小卫星、地月空间转移、深空探测(含载人航天)用推进系统的技术突破与在轨应用。

固体核磁共振技术解析固态电池离子输运机制研究进展

固态电池具有高能量密度和高安全性的特点,是下一代高比能电池的重要发展方向。固态电解质的离子电导率和固态电池多尺度界面性质共同决定固态电池的电化学性能。相比之下,离子在固态电池界面的迁移相对缓慢,这也是提高电化学性能的关键所在。然而传统表征方法有其局限性,无法有效解析固态电池纳米尺度界面对离子传输的影响。固体核磁共振技术可以原位无损地分析局域结构,并对离子传输动力学进行定量分析。本文基于作者所在团队以及国内外先进研究成果,立足于固态电池的离子传输关键科学问题,从固态电解质的离子电导率以及电极电解质界面出发,介绍分析了固体核磁共振技术在研究离子传输方面取得的研究成果。本文首先对固态电池面临的问题进行总结,其次介绍电池研究中常见的固体核磁共振方法,重点介绍了如何通过固体核磁技术解析固态电解质的晶界、离子迁移路径、复合电解质两相界面对传输机制的影响,以及电极电解质界面接触、(电)化学反应和空间电荷层对界面离子传输机制的影响。最后展望了固体核磁共振技术在未来研究固态电池科学问题方面的重要作用。

电化学储能界面的核磁共振谱学研究方法

深入认识电化学储能体系(如锂离子电池与锂金属电池等)表界面层的组成与结构,以及相关的物质传递、电荷存储与转移机理,对于开发宽温区、长循环与高倍率电化学储能器件具有重要的理论指导价值。电化学表界面层呈现出稀薄、无序和敏感等特征,直接观测并获取准确信息充满了挑战。在众多表征技术中,核磁共振技术表现出非侵入性和可定量等特点,是物质鉴别以及微观结构与动力学研究的重要手段。利用原位电化学核磁共振技术还能够观测电化学表界面生成的亚稳态中间相或发生的动态结构演变,为电化学储能体系表界面研究提供了独特而关键的见解。本文综述了电化学储能界面的典型核磁共振研究方法,着重介绍了一维与二维核磁共振技术、同位素示踪技术、动态核极化技术和交叉极化技术以及原位电化学核磁共振技术等方法的基本原理与应用策略。通过上述方法在电极与电解质、复合固态电解质等界面的组成结构、离子输运与界面电荷存储机理等电化学储能界面的应用实例,展示了核磁共振技术在电化学储能界面研究中的应用潜力和重要研究成果。

Intracellular transport of hepatitis B virus

For genome multiplication hepadnaviruses use the tran-scriptional machinery of the cell that is found within the nucleus.Thus the viral genome has to be transported through the cytoplasm and nuclear pore.The intracy-tosolic translocation is facilitated by the viral capsid that surrounds the genome and that interacts with cellular microtubules.The subsequent passage through the nu-clear pore complexes(NPC) is mediated by the nuclear transport receptors importin α and β.Importin α binds to the C-terminus of the capsid protein that comprises a nuclear localization signal(NLS).The exposure of the NLS is regulated and depends upon genome maturation and/or phosphorylation of the capsid protein.As for oth-er karyophilic cargos using this pathway importin α inter-acts with importin β that facilitates docking of the import complex to the NPC and the passage through the pore.Being a unique strategy,the import of the viral capsid is incomplete in that it becomes arrested inside the nuclear basket,which is a cage-like structure on the karyoplas-mic face of the NPC.Presumably only this compartment provides the factors that are required for capsid disas-sembly and genome release that is restricted to those capsids comprising a mature viral DNA genome.

microRNA在非渗出性年龄相关性黄斑变性氧化应激和脂质代谢中的作用

年龄相关性黄斑变性(ARMD)是一种与氧化应激相关的神经退行性疾病,其特征是光感受器和视网膜色素上皮(RPE)细胞的进行性死亡,是导致65岁以上人群不可逆中心视力丧失最常见的原因之一。microRNA(miRNA)是一类调节性短链非编码RNA,能够结合并抑制同一生物途径中的多个基因,这种独特的性质使其成为用于探索非渗出性ARMD发病机制、诊断和治疗的理想靶点。既往研究发现非渗出性ARMD的发病机制涉及年龄、遗传、环境、氧化应激、脂质代谢、自噬和免疫等多方面,但其发病机制尚未完全阐明。miRNA作为非渗出性ARMD的生物标志物在氧化应激和脂质代谢中发挥重要作用,本文总结了多种miRNA通过靶向Nrf2、HIF-1α抑制缺氧相关的血管生成信号影响氧化应激;miRNA通过调节脂蛋白的摄取、RPE和巨噬细胞中ABCA1的表达影响脂质代谢,加深了对miRNA在非渗出性ARMD氧化应激、脂质代谢方面的认识,为完善非渗出性ARMD发病机制和进一步预防提供了帮助。

Theoretical Determination and Experimental Verification of Transport Index of Rectangular Shaped Radioactive Containers

Ionizing radiations are widely used to sustain and enhance our quality of life in the areas such as medical diagnosis, therapy, scientific research and industry etc. Ionizing radiations are available from radioactive sources which are made of radioactive materials. The radioactive materials are produced in either nuclear power or research reactors or nuclear accelerators or extracted from the naturally found radioactive ores. These radioactive sources and radioactive materials need to be transported from their places of production to the places of applications and finally to waste repositories. The radioactive materials are transported in well designed packages having various shapes and sizes. In the field of radioactive transport, it is a mandatory to find the Transport Index (TI) to be mentioned on each package for transportation. This research is focused on the determination of the maximum γ-ray radiation dose at one meter from the surface of cubic and rectangular shaped package or containers. A computer code “Solid Angle for Transport Index” (SAFTI) has been developed using MATLAB to determine the location of maximum value of the radiation dose rate from the surface of a rectangular or square container. This maximum dose rate is used to determine the transport index. Some of the results of the code have been compared with the experimental results. The results of this research are useful not only to determine TI for individual packages but also to find the TI of the vehicles carrying the transport packages.

Atmospheric Dispersion and Deposition of Radionuclides (¹³⁷Cs and ¹³¹I) Released from the Fukushima Dai-ichi Nuclear Power Plant

The Lagrangian Particle Dispersion Model (LPDM) in the 594 km× 594 km model domain with the horizontal grid scale of 3 km×3 km centered at a power plant and the Eulerian Transport Model (ETM) modified from the Asian Dust Aerosol Model 2 (ADAM2) in the domain of 70° LAT × 140° LON with the horizontal grid scale of 27 km×27 km have been developed. These models have been implemented to simulate the concentration and deposition of radionuclides (137Cs and 131I) released from the accident of the Fukushima Dai-ichi nuclear power plant. It is found that both models are able to simulate quite reasonably the observed concentrations of 137Cs and 131I near the power plant. However, the LPDM model is more useful for the estimation of concentration near the power plant site in details whereas the ETM model is good for the long-range transport processes of the radionuclide plume. The estimated maximum mean surface concentration, column integrated mean concentration and the total deposition (wet+dry) by LPDM for the period from 12 March to 30 April 2011 are, respectively found to be 2.975 × 102 Bq m-3, 3.7 × 107 Bq m-2, and 1.78 × 1014 Bq m-2 for 137Cs and 1.96 × 104 Bq m-3, 2.24 × 109 Bq m-2 and 5.96 × 1014 Bq m-2 for 131I. The radionuclide plumes released from the accident power plant are found to spread wide regions not only the whole model domain of downwind regions but the upwind regions of Russia, Mongolia, Korea, eastern China, Philippines and Vietnam within the analysis period.

The Flow of Information from Nucleus to Golgi Is Contingent upon Nuclear Membrane Synthesis and Protraction of the Ceramide-Containing Membrane to Endoplasmic Reticulum

The nucleus-initiated augmentation of ER membrane is reflected in a coordinated synthesis and intercalation of the explicit proteins and lipids required for the replacement, repair and function of the cell and its organelles. The direct connection between nucleus and the membranes containing labeled sphingosine (SphN) and ceramide (Cer) was affirmed by determining synthetic activity of serine palmitoyltransferase (SPT). The SPT and the newly synthesized serine-labeled lipid products were identified in the Outer- and Inner-Nuclear Membrane (ONM, INM) and ER. The pulse-chase experiments disclosed that the incorporation of radiolabeled lipids into both nuclear membranes declined upon their simultaneous increase in Endoplasmic Reticulum (ER). These results, and prior findings regarding metabolic transfer of nuclear membrane phosphoinositides to the outer leaflet of ER [Slomiany and Slomiany, Health, 2011, 3, 187-199], allowed us to reason that INM and ONM are not distinct entities, but uninterrupted continuum facing nucleosol and then cytosol when protracted into segment known as ER. Consequently, the identification of SPT and its products in the inner leaflet of nuclear and ER microsomes lent credence to the luminal presence of Cer in Golgi, luminal synthesis of glycosphingolipids (GSphLs), sphingomyelin (SM), and their delivery to the outer leaflet of apical and basolateral cell membrane, respectively. The findings presented in this communication provide further support to our concept that the factual intercalation of proteins and lipids into the cell membranes can only take place during their simultaneous synthesis that is guided by the nuclear and cytosolic processes enacted in nuclear-ER membrane continuum. At the nuclear stage, the signal-specific genes expression promotes active synthesis and intercalation of lipids into the organelles’ customized membrane that is protracted and articulated in ER in form of transport vesicles.

Nuclear dynamics and particle production near threshold energies in heavy-ion collisions

Recent progress of the quantum molecular dynamics model for describing the dynamics of heavy-ion collisions is viewed, in particular the nuclear fragmentation, isospin physics, particle production and in-medium effect, hadron-induced nuclear reactions, hypernucleus, etc.The neck fragmentation in Fermi-energy heavy-ion collisions is investigated for extracting the symmetry energy at subsaturation densities. The isospin effects, in-medium properties, and the behavior of high-density symmetry energy in medium-and high-energy heavy-ion collisions are thoroughly discussed. The hypernuclide dynamics formed in heavy-ion collisions and in hadron-induced reactions is analyzed and addressed in the future experiments at the high-intensity heavy-ion accelerator facility(HIAF).

Atmospheric pollutants transport tracks revealed from ^(131)I, ^(137)Cs, and ^(134)Cs leaked from Fukushima accident and ~7Be and ^(210)Pb observed at Guiyang of China

A massive earthquake measuring 9.0 on the Richter scale that occurred on March 11, 2011, on Honshu Island, Japan, caused radioactivity leakage from the Fukushima Nuclear Power Plant, which led to the leakage of artificial nuclides(131I, 137 Cs, and 134Cs) and their global transportation by atmospheric circulation. This paper reports a systematic comparative observation on radioactive concentrations of natural nuclides(7Be and 210Pb) and artificial nuclides(131I, 137 Cs, and 134Cs) at the surface level, measured in weekly continuous aerosol sampling at Mount Guanfeng, Guiyang, China, from March 17, 2011 to April 28, 2011. During this period, the variations in the nuclide concentrations associated with their transport paths were analyzed with 315 hour back-trajectories of air mass initialized 500 m above the surface level at Guiyang. The results show that the pollutants of nuclear leakage from the Fukushima accident were transported to the Guiyang region of China via two significant pathways. In the first pathway the first wave of nuclear pollutants were transported from west to east in air masses at higher altitudes via global atmospheric circulation. The nuclear pollutants encircled the Earth almost once and after about 10 days to two weeks, between March 24 and March 31, 2011, intruded Guiyang from the northwestern region of China. In the second pathway, the nuclear pollutants from the Fukushima region arrived at Guiyang between April 7 and April 14, 2011, via air masses at lower altitudes that moved southwards because of the squeezing of the northeast Asian weather system and then by the influence, in succession, of the northeastern and southeastern air currents in the low-latitude region. The first transport pathway for atmospheric pollutants is on a global scale and based on air masses at higher altitudes, and the second transport pathway is on an eastern Asia regional scale and based on the air masses at lower altitude.