In vivo study on the effects of microcystin extracts on the expression profiles of proto-oncogenes (c-fos, c-jun and c-myc) in liver, kidney and testis of male Wistar rats injected i.v. with toxins

Microcystins (MCs) are a potent liver tumor promoter, possessing potent tumor-promoting activity and weak initiating activity. Proto-oncogenes are known to be involved in the tumor-promoting mechanisms of microcystin-LR. However, few data are available on the effects of MCs oil proto-oncogenes in the whole animal. To investigate the effects of MCs on the expression profile of the proto-oncogenes in different organs, male Wistar rats were injected intravenously with microcystin extracts at a dose of 86.7 mu g MC-LR eq/kg bw (MC-LR eq, MC-LR equivalents). mRNA levels of three proto-oncogenes c-fos, c-jun and c-myc in liver, kidney and testis were analyzed using quantitative real-time PCR at several time points post-injection. Significant induction of these genes at transcriptional level was observed in the three organs. In addition, the increase of mRNA expression of all three genes was much higher in liver than in kidney and testis. Meanwhile, the protein levels of c-Fos and c-Jun were investigated by western blotting. Both proteins were induced in the three organs. However, elevations of protein levels were Much lower than those of mRNA levels. These findings suggest that the expression of c-fos, c-jun and c-myc might be one possible mechanism for the tumor-promoting activity and initiating activity of microcystins. (c) 2008 Published by Elsevier Ltd.

条件反射性免疫抑制及其脑机制的c-fos研究

To explore the neural mechanisms underlying conditioned immunomodulation, this study employed the classical taste aversion (CTA) behavioral paradigm to establish the conditioned humoral and cellular immunosuppression (CIS) in Wistar rats, by paring saccharin (CS) with intraperitoneal (i.p.) injection of an immunosuppressive drug cyclophophamide (UCS). C-fos immunohistochemistry method was used to observe the changes of the neuronal activities in the rat brain during the acquisition, expression and extinction of the conditioned immunosuppression (CIS). The followings are the main results: 1. Five days after one trial of CS-UCS paring, reexposure to CS alone significantly decreased the level of the anti-ovalbumin (OVA) IgG in the peripheral serum. Two trials of CS-UCS paring and three reexposures to CS not only resulted in further suppression of the primary immune response, but also reduced the numbers of peripheral lymphocytes and white blood cells. This finding indicates that CS can induce suppression of the immune function, and the magnitude of the effects is dependent on the intensity of training. 2. On day 5 following two trials of CS-UCS pairing, CS suppressed the spleen lymphocytes responsiveness to mitogens ConA, PHA and PWM, and decreased the numbers of peripheral lymphocytes and white blood cells. On day 15, only PHA induced lymphocyte proliferation was suppressed by CS. On day 30, presentation of CS did not have any effect on these immune parameters. These results suggest that the conditioned suppression of the cellular immune function can retain 5-15 days, and extinct after 30 days. 3. CTA was easily induced by one or two CS-UCS parings, and remained robust even after 30 days. These data demonstrate that CIS can be dissociated from CTA, and they may be mediated by different neural mechanisms. 4. Immunohistochemistry assays revealed a broad pattern of c-fos expression throughout the rat brain following the CS-UCS pairing and reexposure to CS, suggesting that many brain regions are involved in CIS. Some brain areas including the solitary tract nucleus (Sol), lateral parabrachial nucleus (LPB) and insular cortex (IC), showed high level c-fos expressions in response to both CS and UCS, suggesting that they may be involved in the transmission and integration of the CS and UCS signals in the brain. There were dense c-FOS positive neurons in the paraverntricular nucleus (PVN) and supraoptic nucleus (SO) of hypothalamus, subfornical organ (SFO) and area postrema (AP) etc. after two trials of CS-UCS paring and after the reexposure to CS 5 days later, but not in the first training and after the extinction of CIS (30 days later). The results reflect that these nuclei may have an important role in CIS expression, and may also response to the immunosuppression of UCS. The conditioned training and reexposure to CS 5 days later induced high level c-fos expression in the cingulate cortex (Cg), central amygdaloid nucleus (Ce), intermediate part of lateral septal nucleus (LSI) and ventrolateral parabrachial nucleus (VLPB) etc. But c-fos induction was not apparent when presenting CS 30 days later. These brain regions are mainly involved in CIS, and may be critical structures in the acquisition and expression of CIS. Some brain regions, including the frontal cortex (Fr), ventral orbital cortex (VO), IC, perirhinal cortex (PRh), LPB and the medial part of solitary nucleus (SolM), showed robust c-FOS expression following the conditioning training and reexposure to CS both on day 5 and day 30, suggesting that they are critically involved in CTA.

饲养层FGF2表达量对猕猴胚胎干细胞自我更新及多能性的影响

用转基因和RNA干扰(RNAi)法建立5组不同成纤维细胞生长因子-2(fibroblast growth factor-2,FGF2)表达量的猕猴耳部皮肤成纤维细胞(MESF)系:过表达FGF2组(f1),过表达的阴性对照组(f2),FGF2 RNA干扰组(f3),RNA干扰的阴性对照组(f4)和未作任何处理的对照组(f5).5组MESF的FGF2表达量相对值为f1:f2:f3:f4:f5=4:2:1:2:2;c-fos,TGF-β1,INHBA,Gremlinl在f1中表达量上升,在f3中表达量下降;BMP4,TGF-β2在f1中表达量下降,在f3中表达量上升;表明内源FGF2能够作用于MESF的TGF-β信号通路,引起相关基因表达量的变化.用这砦细胞作为饲养层长期培养(10代)猕猴胚胎干细胞(RhESC),结果在f1上培养的RhESC增殖速度都比对照组快,并且c-fos,TGF-β1,INHBA,Gremlinl,Oct-4,Nanog,Sox2表达量均上升,BMP4表达下调;在f3上培养的RhESC增殖较慢,BMP4表达上调,c-fos,TGF-β1,INHBA,Gremlinl,Oct-4,Nanog,Sox2表达下调.5组MESF上培养的RhESC形成的EB均表达各胚层早期标记基因(marker),说明RhESC的多能性没有受到影响,但表达量有差异,f1上RhESC形成的EB所有marker都低表达.结果表明饲养层的FGF2含量不仅影响自身相关基凶的表达,还对RhESC的自我更新有一定的作用.

不同FGF-2表达量的饲养层对猕猴和兔胚胎干细胞的增殖和自我更新的影响

胚胎干细胞（ESC）培养是ESC研究的基础，饲养层的选择是ESC培养的一个重要方面。本实验曾对不同的猕猴饲养层进行研究，显示能够更好的支持猕猴ESC生长的饲养层FGF-2表达量也较高。FGF-2，又名bFGF（碱性成纤维生长因子），是ESC生长所需的重要因子，但其中的分子机制现在并未完全了解。本文一方面对ESC相关研究进展进行了综述，另一方面对以下内容进行了研究：用转基因和RNA干（RNAi）扰的方法建立不同FGF-2的表达量猕猴耳部皮肤细胞（MESF）系五组：过表达FGF-2（f1），过表达的阴性对照组（f2），FGF-2 RNA干扰组（f3），RNA干扰的阴性对照组（f4）以及未作任何处理的对照组（f5），这五组MESF的FGF-2表达量相对值为f1：f2：f3：f4：f5＝4：2：1：2：2；c-fos，TGF-β1，INHBA，Gremlin1在f1中表达量上升，在f3中表达量下降；BMP4，TGF-β2在f1中表达量下降，在f3中表达量上升；表明内源FGF-2能够作用于MESF的TGF-β信号通路，引起相关基因表达量的变化。用这些细胞作为饲养层分别培养两种ESC（猕猴ESC，R366. 4和兔ESC，RFESC） ，连续培养了10代，其中在f1上培养的两种ESC增殖速度都比对照组快，并且c-fos，TGF-β1，INHBA，Gremlin1，OCT-4，Nanog，Sox2表达量均上升，BMP4表达下调；在f3上培养的猕猴ESC增殖较慢，BMP4表达上调，c-fos，TGF-β1，INHBA，Gremlin1，OCT-4，Nanog，Sox2表达下调；f3上的兔ESC没有变化。表明ESC中的TGF-β信号通路也受到调节。五组猕猴和兔的ESC形成的EB均表达各胚层早期标记基因(marker)，但表达量有差异，f1上ESC形成的EB所有marker都低表达。实验结果表明饲养层中的FGF-2含量高低不仅影响自身相关基因的表达，还对ESC的增殖和维持自我更新有一定的作用。

情绪应激对大鼠体液免疫功能的影响及其机制

This study was undertaken to investigate the effect of emotional stress on humoral immunoactivity and to examine whether the sympathetic nervous system was involved in the immunomodulation. In the present study, two types of emotional stressors were used. One was footshock apparatus used to cause the rats which were given footshock before, emotional stressed; the other was an empty water bottle used to cause the rats which were trained to drink water at two set times each day, emotional stressed. The effect of emotional stress on the primary immune function (anti-ovallum antibody level and spleen index), the endocrine response (corticosterone level, epinephrine and norepinephrine level), the behavioral changes (freezing, defecation, grooming and attacking behavior) were investigated. The main results were: 1. Two types of emotional stress significantly increased the level of plasma corticosterone, norepinephrine and epinephrine, as well as freezing, defecation and attacking behavior. 2. Two types of emotional stress significantly decreased the level of anti-ovallum antibody. A negative correlation between catecholamine level (epinephrine and norepinephrine) and antibody level or spleen index was found. 3. β-adrenergic receptor antagonist propranolol could reverse the immunomodulation induced by emotional stress. 4. After two types of emotional stress, c-fos expression was observed in the following brain areas or nucleus; arcuate nucleus, anterior commissure nucleus, diffuse part of dorsalmedial nucleus hypothalamus, lateral dorsal nucleus thalamus, medial nucleus amygdala, solitary nucleus, frontal cortex and cingulum. These brain areas and nucleus are involved in the central modulation of the autonomic nervous system. Taken together, these findings demonstrate that emotional stress can suppress humoral immunity and the activation of the sympathetic nervous system is involved in the humoral immunomodulation induced by emotional stress.

Nonequilibrium microstructures and their evolution in a Fe-Cr-W-Ni-C laser clad coating

The laser-solidified microstructural and compositional characterization and phase evolution during tempering at 963 K were investigated using an analytical transmission electron microscope with energy dispersive X-ray analysis. The cladded alloy, a powder mixture of Fe, Cr, W, Ni, and C with a weight ratio of 10:5:1:1:1, was processed with a 3 kW continuous wave CO2 laser. The processing parameters were 16 mm/s beam scanning speed, 3 mm beam diameter. 2 kW laser power, and 0.3 g/s feed rate. The coating was metallurgically bonded to the substrate, with a maximum thickness of 730 mu m, a microhardness of about 860 Hv and a volumetric dilution ratio of about 6%. Microanalyses revealed that the cladded coating possessed the hypoeutectic microstructure comprising the primary dendritic gamma-austenite and interdendritic eutectic consisted of gamma-austenite and M7C3 carbide. The gamma-austenite was a non-equilibrium phase with extended solid solution of alloying elements and a great deal of defect structures, i.e. a high density of dislocations, twins, and stacking faults existed in gamma phase. During high temperature aging, in situ carbide transformation occurred of M7C3 to M23C6 and M6C. The precipitation of M23C6, MC and M2C carbides from austenite was also observed.

铁基抗高温磨损激光熔覆涂层强韧设计和研究II:Fe-Cr-C-W-Ni激光熔覆层的微观组织及性能

本文以对热工模具进行失效分析的基础上，利用激光熔覆技术，在５ＣｒＭｎＭｏ基础上设计并制备强韧兼备的抗高温磨损涂层。

裂纹顶端位错的运动和小范围屈服的K_(Ⅱc)

本文从裂纹顶端位错运动的简化模型估计形成塑性区所消耗的功;从而计算临界裂纹扩展力。由于Ⅰ型加载和Ⅱ型加载的应力状态有所不同,裂纹顶端塑性功耗也会不一样。基于上述思想,考虑了小范围屈服的K_(Ⅰc)和K_(Ⅱc)的关系,得出K(Ⅱc)>K(Ⅰc)的结论,符合实验结果;并就K(Ⅱc)/K(Ⅰc)的比值与材料性能和温度的关系作了讨论。

铁基抗高温磨损激光熔覆涂层强韧设计和研究 Ⅱ:Fe-Cr-C-W-Ni激光熔覆层的微观组织及性能

利用ＯＭ、ＳＥＭ、ＴＥＭ研究了Ｆｅ－Ｃｒ－Ｃ－Ｗ－Ｎｉ激光熔覆涂层熔覆态及其高温时效态的微观组织结构。结果表明激光熔覆层组织细小，具有强韧两相组成（奥氏体和Ｍ_７Ｃ_３碳化物）的微观结构特征，高温时效处理组织中有Ｍ_（２３）Ｃ_６、Ｍ_６Ｃ、Ｍ_２Ｃ等新碳化物形成。显微硬度和冲击磨损实验证实了激光熔覆态和峰值时效态熔覆层均具有良好的力学性能。

钾离子通道Kir2.1/C-末端功能区的分子动力学模拟

<正>内向整流型钾离子通道(Kir,inwardlyrectifyingpotassium)在细胞激活、细胞内外钾离子K~+的动态平衡、胰岛素分泌等细胞生理过程中起重要作用。而细胞内各种不同因素和第二信使对Kir的调控则是实现其不同生理功能的途径。已有实验结果表明,4,5二磷酸磷脂酰肌醇(PIP2,phosphatidylinositol4,5-bisphosphate)与Kir相互作用的强弱决定了Kir对各种调控因素的响应程度。根据Kir2.1与Kir3.1胞内C-末端X-ray

Visual C++ 6.0学习教程

MicrosoftVisualC十十6.0作为Microsoft Visual Studio的重要组成部分，包含了迄今为止功能最为强大的基于Windows的应用框架，在同类产品中处于领先地位。VisualC十十6.0是Microsoft迄今为止最全面、最完善的程序开发工具，为了适应各种编程风格，该软件提供了各种各样的辅助工具，在发挥编程能力和提高灵活性方面达到了空前的水平。与以往VisualC十十的各种版本相比较，VisualC十十6.0在编程环境、程序语言技术等方面做了许多改进，从而使VisualC十十更加适合专业程序员快速进行应用程序的开发。

本书内容丰富、图文并茂，是一本适合各种读者学习VisualC十十6.0的优秀参考书。

目 录
第一章 VisualC十十6.0简介及安装
1.1VisualC十十6.0新特性
1.2viSualC十十6.0开发环境简介
1.3如何学习使用VisualC十十6.0
1.4VisualC十十6.0的安装
第二章 走进C十十的世界
2.1类和对象的简介
2.2继承和多态性――一个具体的例子
2.3内嵌对象
2.4在栈中申请对象
2.5全程对象的申请
2.6对象之间的相互关系――指针数据成员
2.7this指针的使用
2.8对指针的引用
2.9友元类和友元函数
2.10静态类成员
2.11重载运算符
2.12从代码中分离出类定义
2.13匈牙利表示法
第三章 VisualC十十6.0的编程环境
3.1VisualC十十6.0主窗口
3.2VisualC十十6.0工具栏
3.3VisualC十十6.0菜单栏
3.4项目与项目工作区
3.5资源与资源编辑器
第四章 编一个最简单的VC十十程序
4.1什么是AppWizard？
4.2迎接你的第一个AppWizard程序
4.3“Iamaprogrammer.”在哪儿？
第五章 程序框架入门
5.1一个简化过的程序框架
5.2WinMain（）：第一个动作
5.3登记窗口类
5.4创建一个窗口
5.5显示窗口
5.6显示出那条消息
5.7窗口类与窗口对象
第六章 消息循环
6.1在消息循环中兜圈子
6.2对事件做出响应：WindowFun（）
6.3响应不同的消息
6.4现在你还跟得上吗？
6.5设备界面进行交互
第七章 精通程序框架
7.1WinMain（）函数在哪儿？
7.2应用程序框架和源文件
7.3工具条、状态条和打印等选项
7.4程序的控制流程
第八章 使用classWizard编程
8.1使用ClassWizard添加消息处理函数
8.2classWizard功能介绍
8.3传送鼠标消息
8.4保存鼠标绘图的信息
第九章 视图与文档
9.1Document－View模式
9.2从视图中分离出文档
9.3保存文档
9.4再访MyProg2.cpp
第十章 对象连接与嵌入（OLE）及其自动化
10.1公共对象模式（COM）
10.2类厂（classfactory）
10.3OLE自动化
10.4IDispatch接口
第十一章 动态连接库（DLLs）
11.1为什么使用DLL
11.2传统的DLL
11.3MFC库DLL
11.4MyProg4A――编写自己的类库扩展DLL
11.5MyProg4B――使用MFC库扩展DLL
11.6资源访问
第十二章 图形设备接口
12.1设备环境类
12.2GDI对象
12.3Windows的颜色映射
12.4映射方式
12.5字体
12.6MyProg3例程序
12.7MyProg3B程序
12.8MyPr0g3C例程序――使用CScrollView
第十三章 对话框
13.1在状态条上显示对话控件的帮助信息
13.2利用Fi1eOpen通用对话框打开多个文件
13.3定制通用文件对话框
13.4扩展和缩减一个对话框
13.5显示一个模式或无模式对话框
13.6编写定制的DDX/DDV例程
第十四章 剖析工具Spy十＋
14.1窗体
14.2消息
14.3进程与线程
第十五章 代码调试
15.1TRACE
15.2调试框架
15.3自我诊断
15.4调试代码的作用
15.5用Dump（）显示对象的信息
15.6检查内存

Development And Characterization Of Composite Ni-Cr-C-Caf2 Laser Cladding On Gamma-Tial Intermetallic Alloy

A process of laser cladding Ni-CF-C-CaF2 mixed powders to form a multifunctional composite coatingd on gamma-TiAl substrate was carried out. The microstructure of the coating was examined using XRD, SEM and EDS. The coating has a unique microstructure consisting of primary dendrite or short-stick TiC and block Al4C3 carbides reinforcement as well as fine isolated spherical CaF2 solid lubrication particles uniformly dispersed in the NiCrAlTi (gamma) matrix. The average microhardness of the composite coatings is approximately HV 650 and it is 2-factor greater than that of the TiAl substrate. (C) 2008 Elsevier B.V. All rights reserved.

Improved fluorescence from Tm3+/Er3+/Ce3+ triply doped bismuth-silicate glasses for S+C-bands amplifiers

Fluorescence of Tm3+/Er3+ codoped bismuth-silica (BS) glasses and the sensitization of Ce3+ are investigated. It shows that Ce3+ codoping with Tm3+/Er3+ in BS glasses results in a quenching of Tm3+ ion emission from F-3(4) to the H-3(6) level. Consequently, the 1.47 mu m emission occurs after the population inversion between the H-3(4) and F-3(4) levels. Furthermore, the codoped glasses show the broad emission spectra over the whole S and C bands with full-width at half-maximum (FWHM) up to about 119nm, as it combines 1.55 mu m emission band of Er3+ with 1.47 mu m emission band of Tm3+ under 800nm excitation.