Neurotrophic regulation of synapse development and plasticity

Neurotrophic factors are traditionally thought to be secretory proteins that regulate long-tern survival and differe, ntiation of neurons. Recent studies have revealed a previously unexpected role for these factors in synaptie de velopment ami plasticity in diverse neuronal populations. Here we review experimeuts carried oul in our own laboratory in the last few years.. We have made two important discoveries.First,we were among the first to report that brain-derived. neurotrophie faclor (BDNF) facilitates hippocampal hmg-term potentiation (LTP), a form of synaptic plaslicity believed to be involved in learning and memory. BDNF modulates LTP al CAI synapses by enhaneing synaptic responses to high frequency, tetanic slimulalion. This is achieved primafily by facilitating synaptie vesicle doeking, possibly due to an in crease in the levels of the vesicle prolein synaptobrevin and synaptoplysin in the nerve terminals. Gene knockout study demonstrates thai the effects of BDNF are primarily mediated through presynaptic mechanisms. Second, we demonstrated a form of long-term, neurotrophin-mediated synaptic regulation. We showed that long-term treatment of the neuromuscu lar synapses with neurotrophin-3 (NT3) resulted in an enhancement of both spontaneous and evoked synaptic currcuts, as well as profound changes in thc number of synaptic varicosities and syuaptic vesicle proteins in motoneurons, all of which are indicative of more mature synapses. Our current work addresses the following issues:(i) activity-dependent trafficking of neurotrophin receptors, and its role in synapse-specific modulation; (ii) signal transduction mechanisms medialing the acute enhancement of synaplic transmission by neurotrophins; (iii) acute and long-tenn synaptie actions of the GDNF family; (iv) role of BDNF in late-phase LTP and in the development of hippocampal circuit.     

On the self-association potential of transmembrane tight junction proteins

Tight junctions seal intercellular clefts via membrane-related strands, hence, maintaining important organ functions. We investigated the self-association of strand-forming transmembrane tight junction proteins. The regulatory tight junction protein occludin was differently tagged and cotransfected in eucaryotic cells. These occludins colocalized within the plasma membrane of the same cell, coprecipitated and exhibited fluorescence resonance energy transfer. Differently tagged strand-forming claudin-5 also colocalized in the plasma membrane of the same cell and showed fluorescence resonance energy transfer. This demonstrates self-association in intact cells both of occludin and claudin-5 in one plasma membrane. In search of dimerizing regions of occludin, dimerization of its cytosolic C-terminal coiledcoil domain was identified. In claudin-5, the second extracellular loop was detected as a dimer. Since the transmembrane junctional adhesion molecule also is known to dimerize, the assumption that homodimerization of transmembrane tight junction proteins may serve as a common structural feature in tight junction assembly is supported. Received 6 October 2005; received after revision 14 December 2005; accepted 27 December 2005 †These authors contributed equally to this work.     

Regulation of cell adhesion by PP2A and SV40 small tumor antigen: An important link to cell transformation

The serine/threonine protein phosphatase 2A (PP2A) represents a large family of highly conserved heterotrimeric enzymes. Their critical importance in cell homeostasis is underlined by the fact that they are targets of natural toxins like the tumor promoter okadaic acid, and of simian virus 40 small tumor antigen (SV40 small t), a viral protein known to promote cell transformation. Furthermore, mutated or lower expression levels of PP2A subunits have been found in certain cancers. One major known event in PP2A-dependent cell transformation is the alteration of key signaling pathways that control cell growth and survival. In this review, we focus on how PP2A enzymes also affect cell adhesion and cytoskeletal dynamics, the disruption of which is linked to loss of cell polarity, increased cell motility and invasiveness. We also examine how those various pathways participate in the transforming activity of SV40 small t. Received 29 June 2006; received after revision 3 August 2006; accepted 20 September 2006     

Harmonic mixing of Bi2Sr2CaCu2O8+x intrinsic junction at millimeter waveband

Using intrinsic Josephson junctions in Ba₂Sr₂CaCu₂O_8+x single crystal, harmonic frequency mixing at 8 and 3 mm wavebands was successfully demonstrated at liquid nitrogen temperatures with harmonic numbers up to 68 and 50 respectively. The dependences of intermediate frequency output on the local oscillator power and dc bias were carefully studied.     

CoFe/Al2O3/NiFe磁性隧道结的研究

利用离子束溅射技术制备了Ta/CoFe/Al2 O3 /NiFe磁性隧道结 ,研究了它的磁化曲线、磁电阻特性、伏安特性 ,发现它具有明显的巨磁电阻效应 .在研究电流与电压、电流与电阻特性中 ,发现了电流增大到 2 5 μA左右时隧道结呈现伪击穿现象的畸变输运行为 ,还分析了自旋相关散射对电流输运的影响     

硅单晶杂质补偿度对超高反压大功率晶体管耐压特性的影响

一、引言 超高反压大功率晶体管DF104是电视机的重要电子器件。提高其质量和合格率是发展国产电视机的重要课题之一。在严格的器件设计和工艺条件下,采用低补偿度的优质硅单晶材料,能有效地提高这晶体管的击穿电压及其合格率,从而降低其成本。 实验用的衬底硅单晶片是电阻率大体相同(P≈80Ωom)的N-Si。实验时,从同一硅单晶锭切下硅片,用55K低温霍尔法和迭代法抽样检测其杂质补偿度K,再将和抽样检测样品相邻的硅片,经严格抛光清洗之后投片生产晶体管。每次生产条件严格保持相同。对生产出的晶体管,统测其耐压BV_(ceo)和BV_(cbo)及其合格率ξ,η等。合格率ξ和η分别定义为耐压≥某额定耐压BV_(ceo)和BV_(cbo)的成品数对总成品数之比。     

Cholera toxin B-subunit incorporation into synaptic vesicles of the neuromuscular junction of the rat

Summary The B-subunit of cholera toxin, a nontoxic macromolecule which binds specifically to GM1 ganglioside, was conjugated to colloidal gold and injected into skeletal muscle of the rat. It was taken up rapidly in vesicles in the terminal axons at the neuromuscular junctions. Injection of albumin-colloidal gold conjugates resulted in an insignificant uptake. The results indicate that uptake of extracellular macromolecules into the terminal axon of the neuromuscular junction may be greatly enhanced by binding to gangliosides at the presynaptic membrane, and that it may occur without association with vesicular recycling related to transmitter release.The study was supported by grants from the Swedish Medical Research Council (proj. No. 07122).—Part of this study was performed at INSERM U-153, Paris, headed by Dr M. Fardeau.     

Calcitonin gene related peptide stimulates adenylate cyclase activity in rat striated muscle

Summary Rat calcitonin gene related peptide (CGRP) and salmon calcitonin (CT) stimulated adenylate cyclase activity in a dose-dependent manner in the rat diaphragm and in the kidney. The ED₅₀ value of rat CGRP was lower and that of salmon CT was higher in the diaphragm than in the kidney. These results suggest that CGRP stimulates adenylate cyclase activity in the striated muscle by reacting with sites distinct from the site in the kidney.     

二维Josephson结阵列的钉扎及棘轮效应

利用电阻分流结动力学数值模拟了二维Josephson结阵列在六角点阵钉扎下系统的磁通分布,通过测量钉扎强度-电压关系,得到该超导系统的电阻随着钉扎强度增加而减小的规律.同时进一步研究了三角状的非对称钉扎势所产生的棘轮效应.