四周模拟失重大鼠后身动脉平滑肌细胞钾电流的改变

本文采用全细胞膜片钳方法观察4周尾部悬吊大鼠（tail-suspended rats,SUS)隐动脉及肠系膜的动脉第2-6级动脉分支血管平滑肌细胞（vascular smooth muscle cells,VSMCs)钾电流密度的变化,结果表明：SUS大鼠后身动脉VSMCs的静息电位（RP）较对照大鼠（CON）后身动脉VSMCs的RP更负,SUS组隐动脉和肠系膜小鼠后身动脉VSMCs的静息电位（RP）较对照大鼠（CON）后身动脉VSMCs的RP更负,SUS组隐动脉和肠系膜小动脉VSMCs的全细胞钾电流密度较CON组显著增加,其中,SUS组的隐动脉和肠系膜小动脉VSMCs的大电导钙激活钙离子通道（BKca)和电压激活钾离子通道（Kv)电流密度较CON组的BKca和Kv电流密度均显著增加,以上结果提示,VSMCs的超极化及进一步引起的通过电压依赖性钙离子通道的钙内流减少可能是模拟失重引起后身动脉反应性降低的电生理机制之一。     

Changes in potassium currents of vascular smooth muscle cells from hindquarter arteries of 4-wk simulated weightlessness rats

It has been reported by Delp et al and Ma J et al that the vasoreactivity of hindquarter vessels from simulated weightless rats decreased. Many factors may contribute to the depressed vasoreactivity. Because the potassium channels play an important role in regulating the resting potential and contribute to the action of some vasoactive substances, we speculated that the changes of potassium channels may be an electro-physiological mechanism involved in the depressed vasoreactivity of hindquarter vessels due to simulated weightlessness.     

抗病毒感染固有免疫应答的信号转导

入侵病毒的探知和适应性免疫应答启动均依靠固有免疫系统。三种模式识别受体(PRRs)在宿主防御系统第一线占据极其重要地位:Toll样受体、维甲酸诱导基因I样受体、核苷酸结合寡聚化结构域样受体。PRRs识别病原相关分子模式(PAMP)或危险信号分子模式(DAMPs)启动和调节固有免疫和适应性免疫应答。每种PRR都有单独的识别配体和细胞定位。激活的PRRs将信号分子传递给其配体分子(MyD88,TRIF,IRAK,IPS-1),配体活化后作为信使激活信号途径下游激酶(IKK复合物,MAPKs,TBK1,RIP-1)和转录因子(NF-κB,AP-1,IRF3),最终产生细胞因子、趋化因子、促炎细胞因子和I型干扰素。本文重点讨论PRRs信号通路及该领域取得的成果,以期为人类健康和免疫疾病防治提供策略。     

Two Half-Sandwiched Ruthenium (II) Compounds Containing 5-Fluorouracil Derivatives: Synthesis and Study of DNA Intercalation

Two novel coordination compounds of half-sandwiched ruthenium(II) containing 2-(5-fluorouracil)-yl-N-(pyridyl)-acetamide were synthesized, and their intercalation binding modes with calf thymus DNA were revealed by hyperchromism of ultraviolet-visible spectroscopy; the binding constants were determined according to a Langmuir adsorption equation that was deduced on the base of careful cyclic voltammetry measurements. The two compounds exhibited DNA intercalation binding activities with the binding constants of 1.13×10⁶ M^-1 and 5.35 ×10⁵ M^-1, respectively.     

Hepatoma-Derived Growth Factor-Related Protein-3 Is a Novel Angiogenic Factor

Hepatoma-derived growth factor-related protein-3 (Hdgfrp3 or HRP-3) was recently reported as a neurotrophic factor and is upregulated in hepatocellular carcinoma to promote cancer cell survival. Here we identified HRP-3 as a new endothelial ligand and characterized its in vitro and in vivo functional roles and molecular signaling. We combined open reading frame phage display with multi-round in vivo binding selection to enrich retinal endothelial ligands, which were systematically identified by next generation DNA sequencing. One of the identified endothelial ligands was HRP-3. HRP-3 expression in the retina and brain was characterized by Western blot and immunohistochemistry. Cell proliferation assay showed that HRP-3 stimulated the growth of human umbilical vein endothelial cells (HUVECs). HRP-3 induced tube formation of HUVECs in culture. Wound healing assay indicated that HRP-3 promoted endothelial cell migration. HRP-3 was further confirmed for its in vitro angiogenic activity by spheroid sprouting assay. HRP-3 extrinsically activated the extracellular-signal-regulated kinase ½ (ERK1/2) pathway in endothelial cells. The angiogenic activity of HRP-3 was independently verified by mouse cornea pocket assay. Furthermore, in vivo Matrigel plug assay corroborated HRP-3 activity to promote new blood vessel formation. These results demonstrated that HRP-3 is a novel angiogenic factor.     

侧条光唇鱼两邻近地理种群的繁殖生物学特征的差异

2007年7月至2009年6月间,分别于北江中上游及流溪河上游支流采集侧条光唇鱼样本358尾及522尾,对两种群的繁殖生物学特征的差异进行了研究。研究结果显示,两种群雌鱼及雄鱼的最小性成熟年龄均为1 龄,北江种群雌性由1 ~5 龄组成,雄性由1 ~4 组成,性比为雌性：雄性=1:1.73;而流溪河种群雌性由1 ~4 龄组成,雄性由1 ~3 组成,性比为雌性：雄性=1:1.40。北江种群繁殖群体的各年龄组体长及体重均较显著大于流溪河种群。北江种群的繁殖期约为2~10月份,高峰期为3~7月份;而流溪河种群繁殖期为2~8月份,高峰期约为每年的5~7月份;繁殖期内,北江种群雌性及雄性的成熟系数均高于流溪河种群。北江种群各年龄组或体长组的绝对生殖力、体长相对生殖力与体重相对生殖力均极显著地大于流溪河种群。本文结合北江和流溪河在营养状况、捕捞压力及溪流级别上的差异对研究结果进行了分析和讨论。     

神经病靶标酯酶的调节与功能

神经病靶标酯酶(NTE)是一种只催化经CDP-胆碱途径合成的卵磷脂的磷脂酶B,其表达可能受着卵磷脂、环腺苷酸和泛素-蛋白酶体途径的调节。NTE不仅对于胚胎发育和神经系统中非常重要,还在细胞增殖和细胞分化中起着一定的作用。有机磷酸酯可能通过抑制NTE,破坏膜脂稳态,阻碍神经细胞内的物质运输引发轴突损伤的迟发性神经病。     

Cloning of thrombolytic enzyme (lumbrokinase) from earthworm and its expression in the yeast Pichia pastoris

Lumbrokinase (PI239, GenBank Accession No. AF433650) from the earthworm Lumbricus bimastus has been identified. The cDNA of PI239 is composed of 852bp and includes an open reading frame that encodes two parts of the protein: a signal peptide of 44 amino acids and a mature peptide of 239 residues. The cDNA of PI239 exhibits a high degree of sequence identity with other lumbrokinase genes, ranging from 87.6% (F-III-I) to 98.3% (EFE-3). The gene encoding the native form of PI239, with a 5' non-functional end removed, was obtained by PCR amplification and was sub-cloned into pPICZalpha-A, a yeast expression and secretion vector. SDS-PAGE and Western blot analyses showed that rPI239 secreted into the culture medium was specifically recognized by the wild type lumbrokinase polyclonal antibody and was able to dissolve artificial fibrin plates.     

地理来源与生物化学属性对泥炭地植物残体分解的影响

不同地理来源的泥炭地植物残体在同一环境中的分解速率一直缺乏比较研究。该研究沿纬度梯度, 选择大九湖、哈泥和满归3处泥炭地, 以三地的10种植物为分解材料, 使用分解袋包装, 埋藏于长白山哈泥泥炭地, 开展为期1年的分解实验, 研究地理来源及生物化学属性对泥炭地植物残体分解的影响。结果表明, 如不考虑物种差异, 从总体上看, 随着纬度增加, 3处泥炭地植物残体的初始氮(N)含量下降, 初始木质素含量、碳氮比(C/N)和木质素/N上升。经一年分解后残体分解速率因植物类群不同而不同, 桦木属(Betula)和薹草属(Carex)植物残体的干质量损失率均接近50%, 远大于泥炭藓属(Sphagnum)植物(约为10%)。3处来源地植物残体干质量损失率总体上无差异, 但比较同种植物残体发现, 来自中纬度泥炭地哈泥的中位泥炭藓(S. magellanicum)的干质量损失率(19%)远高于来自高纬度泥炭地满归的(9%)。制约残体分解的因素因植物类群不同而不同, 残体初始总酚/N是决定属间残体干质量损失率差异的重要指标。薹草属植物初始N含量和C/N与残体分解速率、泥炭藓属植物初始Klason木质素含量和总酚/N与残体分解速率均呈正相关关系。该研究一定程度上表明, 若以纬度降低指代气候变暖, 当前持续的气候变暖可能通过改变高纬度泥炭地的植物组成和植物的生物化学属性, 来改变植物残体分解速率, 进而影响泥炭地的碳汇功能。     

Inhibition of fibroblast growth by Notch1 signaling is mediated by induction of Wnt11-dependent WISP-1

Fibroblasts are an integral component of stroma and important source of growth factors and extracellular matrix (ECM). They play a prominent role in maintaining tissue homeostasis and in wound healing and tumor growth. Notch signaling regulates biological function in a variety of cells. To elucidate the physiological function of Notch signaling in fibroblasts, we ablated Notch1 in mouse (Notch1(Flox/Flox)) embryonic fibroblasts (MEFs). Notch1-deficient (Notch1(-/-)) MEFs displayed faster growth and motility rate compared to Notch1(Flox/Flox) MEFs. Such phenotypic changes, however, were reversible by reconstitution of Notch1 activation via overexpression of the intracellular domain of Notch1 (NICD1) in Notch1-deficient MEFs. In contrast, constitutive activation of Notch1 signaling by introducing NICD1 into primary human dermal fibroblasts (FF2441), which caused pan-Notch activation, inhibited cell growth and motility, whereas cellular inhibition was relievable when the Notch activation was countered with dominant-negative mutant of Master-mind like 1 (DN-MAML-1). Functionally, "Notch-activated" stromal fibroblasts could inhibit tumor cell growth/invasion. Moreover, Notch activation induced expression of Wnt-induced secreted proteins-1 (WISP-1/CCN4) in FF2441 cells while deletion of Notch1 in MEFs resulted in an opposite effect. Notably, WISP-1 suppressed fibroblast proliferation, and was responsible for mediating Notch1's inhibitory effect since siRNA-mediated blockade of WISP-1 expression could relieve cell growth inhibition. Notch1-induced WISP-1 expression appeared to be Wnt11-dependent, but Wnt1-independent. Blockade of Wnt11 expression resulted in decreased WISP-1 expression and liberated Notch-induced cell growth inhibition. These findings indicated that inhibition of fibroblast proliferation by Notch pathway activation is mediated, at least in part, through regulating Wnt1-independent, but Wnt11-dependent WISP-1 expression.