5-HT2和5-HT3受体在外周初级感觉神经末梢痛反应和痛调制中的相互作用

目的：探讨5-HT2和5-HT3受体亚型在5-HT引起外周痛反应和痛调制中的相互作用及其机制;方法：在大鼠三又神经节神经元标本上应用全细胞膜片钳技术记录5-羟色胺激活电流（15_HT）,并结合痛行为实验进行观察。结果：在大多数受检细胞（54／88,61．4％）特别是中、小型细胞外加5-HT可引起一快去敏感的内向电流,此内向电流能被5-HT,受体特异性激动剂2-甲基-5-羟色胺所模拟,被5-HT3受体拮抗剂ICS250-930可逆性阻断,而5-HT2受体激动剂α-甲基-5-羟色胺则有明显增强15-HT的作用,5-HT1受体激动剂R-（＋）-UH301无明显反应。在进一步的整体清醒动物的行为学试验中我们观察到,大鼠后肢掌底皮下注射5-HT（10-5,10-4和10-3mol／L）引起浓度依赖性的痛行为反应,而用5-HT2和5-HT3受体特异性拮抗剂Cyproheptadine和ICS250-930分别阻断相应受体亚型后,5-HT引起的痛行为反应的强度序列为：5-HT〉5-HT＋ICS〉5-HT＋Cyp。结论：本文结果提示：5-HT所引起的痛反应中,在初级感觉神经元水平5-HT3受体可能仅起着启始作用,而5-HT,受体则在伤害性信息的维持和调制过程中发挥更大的作用。     

Genetic analysis,molecular tagging and mapping of the thermo-sensitive genic male-sterile gene (wtms1) in wheat

A thermo-sensitive genic male-sterile (TGMS) wheat line ( Triticum aestivum L.) BNY-S was obtained from the spontaneous mutant of BNY-F. Its fertility was decided by the temperature during the differentiation stage of the spikelets. BNY-S was completely sterile when the temperature was lower than 10 degrees C during the differentiation stage of the spikelets, but fertile when the temperature was higher than 10 degrees C. Genetic analysis indicated that the sterility of BNY-S was controlled by a single recessive gene, which was named as wtms1. An F(2) population, consisting of 3,000 individuals from the cross between BNY-S and Lankao 52-24, was used for genetic analysis and statistical analysis of the TGMS and, out of them, 158 sterile and 93 fertile extremes were present for molecular tagging and mapping of the wtms1 gene. SSR (simple sequence repeat) and AFLP (amplified fragment length polymorphism) techniques combined with BSA (bulked segregant analysis) were used to screen markers linked to the target gene. As a result, wtms1 was preliminarily mapped on chromosome 2B according to SSR analysis. In AFLP analysis, 14 polymorphic AFLP loci were identified with a linkage relation to the wtms1 gene. Then linkage analysis using the F(2) population showed that three of them, E: AAG/M: CTA(163), E: AGG/M: CTC(220) and E: ACA/M: CTA(160), were linked to the wtms1 gene relatively close to a genetic distance of 6.9 cM, 6.9 cM and 13.9 cM, respectively. Finally, the wtms1 gene was mapped between the SSR marker Xgwm 374 and the AFLP marker E: AAG/M: CTA(163) with the distance of 4.8 cM and 6.9 cM, respectively. A partial linkage map was constructed according the SSR and AFLP data.     

Vascular endothelial growth factor causes translocation of p47phox to membrane ruffles through WAVE1

Growth factors initiate cytoskeletal rearrangements tightly coordinated with nuclear signaling events. We hypothesized that the angiogenic growth factor, vascular endothelial growth factor (VEGF), may utilize oxidants that are site-directed to a complex critical to both cytoskeletal and mitogenic signaling. We identified the WASP-family verprolin homologous protein-1 (WAVE1) as a binding partner for the NADPH oxidase adapter p47phox within membrane ruffles of VEGF-stimulated cells. Within 15 min of VEGF stimulation, p47phox coprecipitated with WAVE1, with the ruffle and oxidase agonist Rac1, and with the Rac1 effector PAK1. VEGF also increased p47phox phosphorylation, oxidant production, and ruffle formation, all of which were dependent upon PAK1 kinase activity. The antioxidant Mn (III) tetrakis(4-benzoic acid) porphyrin and ectopic expression of either the p47-binding WAVE1 domain or the WAVE1-binding p47phox domain decreased VEGF-induced ruffling, whereas the active mutant p4-(S303D, S304D,S328D) stimulated oxidant production and formation of circular dorsal ruffles. Both kinase-dead PAK1-(K298A) and Mn (III) tetrakis(4-benzoic acid) porphyrin decreased c-Jun N-terminal kinase (JNK) activation by VEGF, whereas dominant-negative JNK did not block ruffle formation, suggesting a bifurcation of mitogenic and cytoskeletal signaling events at or distal to the oxidase but proximal to JNK. Thus, WAVE1 may act as a scaffold to recruit the NADPH oxidase to a complex involved with both cytoskeletal regulation and downstream JNK activation.     

大鼠肠道内NOS与AChE、VIP阳性神经元的分布关系研究

应用一氧化氮合酶 (NOS)、乙酰胆碱酯酶 (ACh E)组织化学及血管活性肠肽 (VIP)免疫组织化学方法 ,光镜下比较观察大鼠肠道内 NOS、ACh E、VIP阳性神经元的形态学特征。结果显示 ,肠肌间丛 NOS阳性神经元胞体大小不等 ,形态不一 ,NOS、ACh E和 VIP阳性神经元的分布密度为 ACh E>NOS>VIP,在不同的肠段和层次分布密度有差异 ,NOS与 ACh E存在共染。在肌间丛和粘膜下丛 ,少数 VIP与 NOS共染。在粘膜下丛 ,三种阳性神经元的分布密度为 ACh E>VIP>NOS。在肌间丛和粘膜下丛 ,可见 VIP阳性末梢环抱 NOS阳性神经元胞体 ,两者呈终扣样接触。上述结果提示 NOS阳性神经元与 ACh E、 VIP阳性神经元有密切的形态学联系。在消化道功能调节上 ,它们可能起协调作用。     

供氧对产丙三醇假丝酵母科丙三醇发酵研究

研究了产丙三醇假丝酵母（Ｃａｎｄｉｄａ ｇｌｙｃｅｒｏｌｇｅｎｅｓｉｓ）产丙三醇及副产物与氧供给的关系。摇瓶试验发现其它营养条件一定,玉米浆添加量决定酵母量。在０．４％的玉米浆和装液比０．０８时产丙醇最高,副产物乙醇、乙酸和乙酸乙酯最小,玉米浆和装液比影响丙三醇和副产物的形成。在５Ｌ的反应器中以搅拌转速控制供氧水平,菌体生长阶段比耗氧速率为２８ｍｇ／（ｇ．ｈ）,在发酵阶段比耗氧速率１６ｍｇ／（ｇ．     

景观空间格局对滇金丝猴猴群分布的影响

结合景观生态学,建立研究区域景观格局分析与内部生物之间的联系,能够为生物多样性保护和自然保护区的管理提供更加真实准确及可实践操作的指导。借助遥感和地理信息系统软件,将滇金丝猴分布区内景观划分为适宜生境、次适宜生境、连接生境、天然阻碍及人为干扰5种类型,通过计算得到5种类型斑块的景观指数,并将其与滇金丝猴猴群出现概率及种群密度进行相关性分析。结果表明:(1)滇金丝猴猴群出现概率受人为干扰斑块影响较大,与人为干扰斑块面积所占比例呈负相关,与人为干扰斑块的权重边界密度呈正相关;(2)影响猴群分布密度的景观指数较多,其中除适宜生境斑块所占面积比及其权重边界密度与猴群密度呈正相关之外,其他指数均与猴群密度呈负相关;(3)现阶段对滇金丝猴生境保护最为直接的方法应该是增加适宜生境和次适宜生境斑块间的连通性,即增强这两类斑块的自然增扩潜力,同时减少人为干扰对猴群的影响;(4)对于自然保护的管理应当更加重视边界效应的作用,尽量保持适宜生境与其性质相近类型斑块的连通性,以提高景观质量。     

Beneficial Effects of Caloric Restriction on Chronic Kidney Disease in Rodent Models: A Meta-Analysis and Systematic Review

Background

Numerous studies have demonstrated the life-extending effect of caloric restriction. It is generally accepted that caloric restriction has health benefits, such as prolonging lifespan and delaying the onset and progression of CKD in various species, especially in rodent models. Although many studies have tested the efficacy of caloric restriction, no complete quantitative analysis of the potential beneficial effects of reducing caloric intake on the development and progression of CKD has been published.

Methods

All studies regarding the relationship between caloric restriction and chronic kidney diseases were searched in electronic databases, including PubMed/MEDLINE, EMBASE, Science Citation Index (SCI), OVID evidence-based medicine, Chinese Bio-medical Literature and Chinese science and technology periodicals (CNKI, VIP, and Wan Fang). The pooled odds ratios (OR) and 95% confidence intervals (95% CI) were calculated by using fixed- or random-effects models.

Results

The data from 27 of all the studies mentioned above was used in the Meta analysis. Through the meta-analysis, we found that the parameter of blood urea nitrogen, serum creatinine and urinary protein levels of the AL group was significant higher than that of the CR group, which are 4.11 mg/dl, 0.08mg/dl and 33.20mg/kg/24h, respectively. The incidence of the nephropathy in the caloric restriction (CR) group was significantly lower than that in the ad libitum—fed (AL) group. We further introduced the subgroup analysis and found that the effect of caloric restriction on the occurrence of kidney disease was only significant with prolonged intervention; the beneficial effects of CR on the 60%-caloric-restriction group were greater than on the less-than-60%-caloric-restriction group, and caloric restriction did not show obvious protective effects in genetically modified strains. Moreover, survival rate of the caloric restriction group is much higher than that of the ad libitum—fed (AL) group.

Conclusions

Our findings demonstrate for the first time that compared with the AL group, the caloric restriction indeed decreased urea nitrogen, creatinine, urine protein, incidence of kidney diseases and increased the survival rate on 700~800 days.     

金属螯合亲和层析纯化金属硫蛋白

将二价铜离子螯合在Chelating Sepharose Fast Flow凝胶上制成亲和层析柱,锌诱导兔肝和镉诱导小鼠肝经匀浆、乙醇处理后上柱,用pH4.0的醋酸盐缓冲液平衡,再用pH5.2不同浓度的醋酸盐缓冲液分别洗脱,可得两个金属硫蛋白(MT)洗脱峰,经确定先后为MT-2和MT-1.分离方法比传统的凝胶过滤-离子交换法简单、省时,适于实验室规模分离纯化.     

Syntheses and EGFR and HER-2 kinase inhibitory activities of 4-anilinoquinoline-3-carbonitriles: analogues of three important 4-anilinoquinazolines currently undergoing clinical evaluation as therapeutic antitumor agents

The syntheses and biological evaluations of 4-anilinoquinoline-3-carbonitrile analogues of the three clinical lead 4-anilinoquinazolines Iressa, Tarceva, and CI-1033 are described. The EGFR and HER-2 kinase inhibitory activities and the cell growth inhibition of the two series are compared with each other and with the clinical lead EKB-569. Similar activities are observed between these two series.