Excitatory glycine receptors containing the NR3 family of NMDA receptor subunits

The N-methyl-D-aspartate subtype of glutamate receptor (NMDAR) serves critical functions in physiological and pathological processes in the central nervous system, including neuronal development, plasticity and neurodegeneration. Conventional heteromeric NMDARs composed of NR1 and NR2A-D subunits require dual agonists, glutamate and glycine, for activation. They are also highly permeable to Ca2+, and exhibit voltage-dependent inhibition by Mg2+. Coexpression of NR3A with NR1 and NR2 subunits modulates NMDAR activity. Here we report the cloning and characterization of the final member of the NMDAR family, NR3B, which shares high sequence homology with NR3A. From in situ and immunocytochemical analyses, NR3B is expressed predominantly in motor neurons, whereas NR3A is more widely distributed. Remarkably, when co-expressed in Xenopus oocytes, NR3A or NR3B co-assembles with NR1 to form excitatory glycine receptors that are unaffected by glutamate or NMDA, and inhibited by D-serine, a co-activator of conventional NMDARs. Moreover, NR1/NR3A or -3B receptors form relatively Ca2+-impermeable cation channels that are resistant to Mg2+, MK-801, memantine and competitive antagonists. In cerebrocortical neurons containing NR3 family members, glycine triggers a burst of firing, and membrane patches manifest glycine-responsive single channels that are suppressible by D-serine. By itself, glycine is normally thought of as an inhibitory neurotransmitter. In contrast, these NR1/NR3A or -3B 'NMDARs' constitute a type of excitatory glycine receptor.     

英国国际合作格局

该报告运用文献计量学方法，对英国及其主要合作伙伴国的国际合作格局做了全面的分析。所选
择的主要国家包括美国、加拿大、法国、德国、日本、澳大利亚、中国与印度；数据覆盖领域有临床、医药
卫生、生物科学、环境科学、数学、物质科学以及工程技术领域；数据时间分为1996－2000年与2001－2005
年两个时间段。结果显示：国际论文数量增长显著；英国国际合作论文份额的增长比G7 国家更加快速； 德
国和美国是英国最大的国际合作伙伴；英国国际合作论文的平均影响力显著高于其科研论文的总体影响力；
中国与英国合作发表的论文数量超过了与其他欧洲各国的合作论文数。     

科学新格局：英国科研及其国际合作

国际合作研究不仅可以利用其他国家的科研投资，而且能够产生具有轰动效应的创新型结果。由
于语言文化的相似性，英国与美国及欧洲国家有着较为广泛的联系，他们之间的合作是英国科学研究合作的
主体。随着科学研究及技术革新的发展更多地转向东方，以及中国和印度这两大科技力量的迅猛发展，英国
应该更加重视与这两个国家的合作。文章指出：应该就英国及其新伙伴之间的关系进行详细的研究，从而深
入理解中英两国间的合作并建立成功的合作模式。     

Induction of vanilloid receptor channel activity by protein kinase C

Capsaicin or vanilloid receptors (VRs) participate in the sensation of thermal and inflammatory pain. The cloned (VR1) and native VRs are non-selective cation channels directly activated by harmful heat, extracellular protons and vanilloid compounds. However, considerable attention has been focused on identifying other signalling pathways in VR activation; it is known that VR1 is also expressed in non-sensory tissue and may mediate inflammatory rather than acute thermal pain. Here we show that activation of protein kinase C (PKC) induces VR1 channel activity at room temperature in the absence of any other agonist. We also observed this effect in native VRs from sensory neurons, and phorbol esters induced a vanilloid-sensitive Ca2+ rise in these cells. Moreover, the pro-inflammatory peptide, bradykinin, and the putative endogenous ligand, anandamide, respectively induced and enhanced VR activity, in a PKC-dependent manner. These results suggest that PKC may link a range of stimuli to the activation of VRs.