Cellular internalization of proinsulin C-peptide

Proinsulin C-peptide is known to bind specifically to cell membranes and to exert intracellular effects, but whether it is internalized in target cells is unknown. In this study, using confocal microscopy and immunostained or rhodamine-labeled peptide, we show that C-peptide is internalized and localized to the cytosol of Swiss 3T3 and HEK-293 cells. In addition, transport into nuclei was found using the labeled peptide. The internalization was followed at 37°C for up to 1 h, and was reduced at 4°C and after preincubation with pertussis toxin. Hence, it is concluded to occur via an energy-dependent, pertussis toxin-sensitive mechanism and without detectable degradation within the experimental time course. Surface plasmon resonance measurements demonstrated binding of HEK-293 cell extract components to C-peptide, and subsequent elution of bound material revealed the components to be intracellular proteins. The identification of C-peptide cellular internalization, intracellular binding proteins, absence of rapid subsequent C-peptide degradation and apparent nuclear internalization support a maintained activity similar to that of an intracrine peptide hormone. Hence, the data suggest the possibility of one further C-peptide site of action. Received 31 October 2006; received after revision 27 December 2006; accepted 30 December 2006     

G蛋白偶联受体研究进展

G蛋白偶联受体（GPCRs）是体内最大的蛋白质超家族，根据结构的同源性，主要分为A、B、C3族．GPCRs配体的多样性决定配体结合域的多样性．受体分子内相互作用力的破坏、质子化、构象改变、与G蛋白的偶联及受体二聚化参与了GPCRs的活化过程，近年发现GPCRs的失敏和内吞对受体功能调节亦非常重要，本文拟综述以上内容的研究进展．     

越轨社会学视角下的审判行为瑕疵控制机制及其运行机理

从越轨社会学的视角来看，审判行为瑕疵即指法官在审判中实施的越轨行为，其控制机制不外乎制裁、奖励和内化三种类型。然而，这三者皆有局限性，在实践中须相互补充、共同作用才能有效发挥对审判行为瑕疵的控制功能。     

科技成果转化与我国企业发展分析

科技成果转化水平受社会经济制度、社会发展水平、企业科技吸收能力等条件的制约，由于我国企业发展层次不同，科技成果转化的途径也有所差异，大中型企业走内部化道路．小型企业通过技术市场获取科技成果，总的趋势是促进科技成果企业内部化。     

Nitric oxide mediates histamine induced down-regulation of H<Subscript>2</Subscript> receptor mRNA and internalization of the receptor protein (R1)

During agonist-dependent long-term stimulation of cells, histamine receptor subtypes are frequently down-regulated. However, the mechanisms underlying the modulation of receptor expression during long-term histamine stimulation have yet to be resolved. Based on our recently reported results showing an H₁-mediated down-regulation of histamine H₂ receptor mRNA in endothelial cells, our aim was to characterize the mechanism controlling rapid and long-term histamine-mediated modulation of H₂ receptor expression in more detail. We were able to show that the histamine-induced down-regulation of H₂ receptor mRNA and cell surface expression lasting for 24 h was accompanied by augmentation of the receptor protein level in the cytoplasmatic fraction of endothelial cells for this time period. Furthermore, changes in receptor protein levels in whole-cell lysate were negligible, indicating that the rapid and prolonged modulation of cell surface H₂ receptor levels by histamine was regulated solely via internalization. The role of nitric oxide (NO) as a key mediator in histamine-stimulated cell responses was underlined by subsequent studies showing the attenuation of histamine-induced H₂ receptor mRNA down-regulation and protein trafficking following NO synthase isozyme inhibition.Received 11 March 2003; received after revision 11 June 2003; accepted 17 June 2003     

论中国高等教育国际化的几个问题

该文阐述了高等教育国际化的科学内涵，揭示了中国高等教育国际化的必然性，分析了我国高等教育国际化存在的问题与障碍，指出了我国高等教育国际化的对策与路径选择。     

服务业外商直接投资动因分析

从邓宁的国际生产折衷理论出发,从所有权优势,内部化优势以及区位优势的角度,并以中国为例,具体阐述了外商对华服务业直接投资的动因。     

西藏旅游发展中的负外部效应及其内化研究

西藏旅游发展中负外部性表现在以下几个方面：一是季节性集中的大量游客导致的环境成本;二是旅游对藏民族传统文化生态的破坏引起的社会成本;三是旅游对西藏其他产业的＂挤出效应＂所导致的机会成本。文章认为促使外部效应内部化,减少西藏旅游外部效应的对策包括政府运用税收、补贴、押金、保证金等经济手段实现旅游企业外部成本内部化;合理界定旅游资源产权,防止＂公地悲剧＂发生;建立民族生态博物馆,实行民族文化＂前台、帷幕、后台＂开发与保护模式;对旅游项目进行综合成本—收益分析,追求旅游综合效益最大化。     

交通社会成本内部化与我国电动车的市场化

分析了城市交通社会成本对清洁型交通工具电动车市场化的影响,给出了电动车市场化的经济基本条件;从城市交通的可持续发展、平衡利用能源和加强环境保护的角度论述和探讨了通过城市交通社会成本内部化来促进电动车市场化的途径和扶持力度,并提出了相应的对策     

交通运输外部成本评估及内部化

综合分析了交通运输外部成本的影响和评价结果,指出外部成本评价在对运输外部影响进行货币化估值方面所作出的贡献,并对外部成本内部化效果进行了经济分析,给出了实施外部成本内部化的策略．