Adult neural function requires MeCP2

Rett syndrome (RTT) is a postnatal neurological disorder caused by mutations in MECP2, encoding the epigenetic regulator methyl-CpG-binding protein 2 (MeCP2). The onset of RTT symptoms during early life together with findings suggesting neurodevelopmental abnormalities in RTT and mouse models of RTT raised the question of whether maintaining MeCP2 function exclusively during early life might protect against disease. We show by using an inducible model of RTT that deletion of Mecp2 in adult mice recapitulates the germline knock-out phenotype, underscoring the ongoing role of MeCP2 in adult neurological function. Moreover, unlike the effects of other epigenetic instructions programmed during early life, the effects of early MeCP2 function are lost soon after its deletion. These findings suggest that therapies for RTT must be maintained throughout life.     

Wnt gradient formation requires retromer function in Wnt-producing cells

Wnt proteins function as morphogens that can form long-range concentration gradients to pattern developing tissues. Here, we show that the retromer, a multiprotein complex involved in intracellular protein trafficking, is required for long-range signaling of the Caenorhabditis elegans Wnt ortholog EGL-20. The retromer functions in EGL-20-producing cells to allow the formation of an EGL-20 gradient along the anteroposterior axis. This function is evolutionarily conserved, because Wnt target gene expression is also impaired in the absence of the retromer complex in vertebrates. These results demonstrate that the ability of Wnt to regulate long-range patterning events is dependent on a critical and conserved function of the retromer complex within Wnt-producing cells.     

灰斑病菌毒素对玉米植株防御酶系活性的影响及诱导抗性作用

【目的】探讨玉米灰斑病菌毒素对抗、感自交系的诱抗机理及效果。【方法】测定不同质量浓度玉米灰斑病菌毒素处理及不同毒素处理时间后,玉米植株苯丙氨酸解氨酶(PAL)、过氧化物酶(POD)、多酚氧化酶(PPO)、过氧化氢酶(CAT)和超氧化物歧化酶(SOD)等防御酶系活性的变化,研究玉米灰斑病菌毒素对寄主防御酶系活性的影响及毒素与诱导抗性的关系。【结果】抗病自交系78599-1的PAL、POD和PPO活性高于感病自交系K12,而感病自交系的CAT和SOD活性高于抗病自交系。微晶纤维素处理毒素的诱抗效果高于炭柱处理,玉米抗病自交系的诱抗作用略高于感病自交系。【结论】玉米灰斑病菌毒素对灰斑病具有诱导抗性作用。     

腰果壳油抑菌及杀虫活性的初步研究

以苹果树腐烂病菌等11种植物病原真菌为供试菌,以甘蓝蚜虫为供试虫,评价了腰果壳油的抑菌杀虫活性.结果表明,腰果壳油对11种病原真菌均有不同程度的抑制作用,其中对苹果树腐烂病菌的效果最好,48 h的EC50为0.169 g·L-1(y=1.101x+3.648,r2=0.992 0);腰果壳油对蚜虫具有较好的毒杀作用,72 h的LC50为10.692 g·L-1(y=1.752 4x+3.1967,r2=0.907 7).研究结果对于开发环境友好农药以及充分利用腰果壳油均具有重要意义.     

Accuracy of in vivo aminoacylation requires proper balance of tRNA and aminoacyl-tRNA synthetase

The fidelity of protein biosynthesis in any cell rests on the accuracy of aminoacylation of tRNA. The exquisite specificity of this reaction is critically dependent on the correct recognition of tRNA by aminoacyl-tRNA synthetases. It is shown here that the relative concentrations of a tRNA and its cognate aminoacyl-tRNA synthetase are normally well balanced and crucial for maintenance of accurate aminoacylation. When Escherichia coli Gln-tRNA synthetase is overproduced in vivo, it incorrectly acylates the supF amber suppressor tRNA(Tyr) with Gln. This effect is abolished when the intracellular concentration of the cognate tRNA(Gln2) is also elevate. These data indicate that the presence of aminoacyl-tRNA synthetase and the cognate tRNAs in complexed form, which requires the proper balance of the two macromolecules, is critical in maintaining the fidelity of protein biosynthesis. Thus, limits exist on the relative levels of tRNAs and aminoacyl-tRNA synthetases within a cell.     

Fear erasure in mice requires synergy between antidepressant drugs and extinction training

Antidepressant drugs and psychotherapy combined are more effective in treating mood disorders than either treatment alone, but the neurobiological basis of this interaction is unknown. To investigate how antidepressants influence the response of mood-related systems to behavioral experience, we used a fear-conditioning and extinction paradigm in mice. Combining extinction training with chronic fluoxetine, but neither treatment alone, induced an enduring loss of conditioned fear memory in adult animals. Fluoxetine treatment increased synaptic plasticity, converted the fear memory circuitry to a more immature state, and acted through local brain-derived neurotrophic factor. Fluoxetine-induced plasticity may allow fear erasure by extinction-guided remodeling of the memory circuitry. Thus, the pharmacological effects of antidepressants need to be combined with psychological rehabilitation to reorganize networks rendered more plastic by the drug treatment.     

菌类多糖的生物活性与结构关系

真菌多糖是从真菌中分离出的由10个以上的单糖以糖苷键连接而成的高分子多聚物。真菌多糖倍受关注首先是日本人（1969年）千原从香菇中分离出抗肿瘤活性的多糖而轰动整个医药界，全世界掀起了一股从食用菌中寻找抗肿瘤成分的高潮。实验表明真菌多糖可通过淋巴细胞、巨噬细胞、网状内皮系统的作用而调节机体的免疫功能，提高身体抵抗病毒和细菌的入侵的能力。[第一段]     

己唑醇衍生物的合成及其抑菌性能研究

为了提高己唑醇的杀菌广谱性以及杀菌活性,参考己唑醇的化学结构,以戊酰氯和取代苯为原料,经傅克酰基化、Corey-Chaykovsky环氧化反应、开环反应得到8种化合物,所有化合物均经质谱和核磁共振氢谱确证。选取常用木材腐朽菌——白腐菌(彩绒革盖菌、乳白耙齿菌)、褐腐菌(密粘褶菌、绵腐卧孔菌)和霉菌——黑曲霉作为实验菌株,采用滤纸片法研究8种目标化合物的抑菌活性。结果表明:在质量分数0.5%~2.0%范围内,除化合物A4、A5外,其余化合物对彩绒革盖菌、乳白耙齿菌、密粘褶菌、绵腐卧孔菌和黑曲霉均有一定的抑菌效果,其抑菌能力随着药液浓度的增加而增强。通过与己唑醇对照可知,化合物C3总体抑菌效果最好,并优于己唑醇;化合物C2对腐朽菌的抑菌效果优于己唑醇,对黑曲霉的抑菌效果弱于己唑醇;化合物A1、A2、A3、C1的抑菌效果均弱于己唑醇;化合物A4、A5对木材腐朽菌和霉菌几乎没有抑制作用。可见,卤素(F、Cl)对苯环2,4-二位上的取代、叔醇碳上异丁基的引入均有利于提高目标化合物的抑菌活性。      

茶多酚的抑菌活性研究

采用平板计数法和滤纸片法研究了茶多酚对细菌、酵母和霉菌的抑菌活性及茶多酚质量浓度、pH值、温度和食盐质量浓度对抑菌活性的影响.结果表明:茶多酚对细菌有较强的抑菌活性,而对供试的酵母和霉菌抑制作用不明显;茶多酚对供试菌种的最低抑菌质量浓度不超过1.0 g·L-1,最佳抑菌质量浓度为4.0 g·L-1;在自然pH值和中性偏碱性环境中的抑菌活性比强碱性环境的抑菌活性强;一定温度内处理不影响茶多酚的抑菌活性;食盐可增强茶多酚的抑菌活性.表6参18     

Tumor necrosis factor signaling requires iRhom2 to promote trafficking and activation of TACE

The cytokine tumor necrosis factor (TNF) is the primary trigger of inflammation. Like many extracellular signaling proteins, TNF is synthesized as a transmembrane protein; the active signal is its ectodomain, which is shed from cells after cleavage by an ADAM family metalloprotease, ADAM17 (TNFα-converting enzyme, TACE). We report that iRhom2 (RHBDF2), a proteolytically inactive member of the rhomboid family, is required for TNF release in mice. iRhom2 binds TACE and promotes its exit from the endoplasmic reticulum. The failure of TACE to exit the endoplasmic reticulum in the absence of iRhom2 prevents the furin-mediated maturation and trafficking of TACE to the cell surface, the site of TNF cleavage. Given the role of TNF in autoimmune and inflammatory diseases, iRhom2 may represent an attractive therapeutic target.     

T cell antigen receptor-mediated activation of phospholipase C requires tyrosine phosphorylation

Triggering of the antigen-specific T cell receptor-CD3 complex (TCR-CD3) stimulates a rapid phospholipase C-mediated hydrolysis of inositol phospholipids, resulting in the production of second messengers and in T cell activation and proliferation. The role of tyrosine phosphorylation in these events was investigated with a tyrosine protein kinase (TPK) inhibitor, genistein. At doses that inhibited TPK activity and tyrosine phosphorylation of the TCR zeta subunit, but not phospholipase C activity, genistein prevented TCR-CD3-mediated phospholipase C activation, interleukin-2 receptor expression, and T cell proliferation. These findings indicate that tyrosine phosphorylation is an early and critical event that most likely precedes, and is a prerequisite for, inositol phospholipid breakdown during receptor-mediated T cell activation.     

Centromeric Aurora-B activation requires TD-60, microtubules, and substrate priming phosphorylation

The chromosome passenger complex (CPC) controls chromosome congression, kinetochore-microtubule attachments, and spindle checkpoint signaling during mitosis. Aurora-B kinase is the catalytic subunit of the CPC. To understand how a single kinase can regulate such diverse events, we have investigated the activation of Aurora-B and describe two distinct activation mechanisms. First, Aurora-B activation in vitro requires two cofactors, telophase disc-60kD (TD-60) and microtubules. TD-60 is critical to localize both the CPC and Haspin kinase activity to centromeres and thus regulates Aurora-B at several levels. Second, Aurora-B substrates can inhibit kinase activation, and this is relieved by phosphorylation of these substrates by the centromeric kinases Plk1 and Haspin. These regulatory mechanisms suggest models for phosphorylation by Aurora-B of centromeric substrates at unaligned chromosomes and merotelic attachments.     

休闲观光农业与户外运动的复合开发策略及实证研究

休闲观光农业为户外运动提供了良好的开发平台,而发展户外运动能拓展休闲观光农业发展空间,增强其发展动力,提高综合开发效益.提出休闲观光农业与户外运动复合开发框架,及相应的产品整体开发、项目耦合经营、品牌联合推广等开发策略,包括景观环境乡土化和生态化建设、活动体验化设计、文化有形化展示、经营模式合理设计、管理人才分类开发、品牌联合推广等6个方面,并以杭州富阳市永安高山农庄为例进行了实证分析.     

别隐品碱衍生物的合成及其生物活性

【目的】测定别隐品碱化合物抗植物病原真菌和杀灭兔痒螨的活性,为后续结构优化和药品研发提供依据。【方法】以从博落回中分离的别隐品碱为原药,对其十元氮杂环进行结构修饰,合成了12种衍生物A1～A12,采用质谱(ESI-MS)、核磁共振谱(1 H NMR和13 C NMR)对其结构进行表征。以嘧菌酯为阳性对照,采用菌丝生长速率法,测定50μg/mL目标化合物对6种常见植物病原真菌(苹果腐烂病菌(Valsa mali)、番茄早疫病菌(Alternaria solani)、小麦赤霉病菌(Fusarium graminearum)、玉米弯孢病菌(Curvularia lunata)、马铃薯干腐病菌(Fusarium solani)、水稻稻瘟病菌(Pyricularia oryza))的体外抗菌活性;采用浸虫法检测5mg/mL目标化合物对兔痒螨(Psoroptes cuniculi)的体外杀灭活性。【结果】确认了12种别隐品碱衍生物的结构,它们对供试菌均具有不同程度的抑制活性,对兔痒螨具有一定的杀灭活性。其中,以化合物A11的抑菌活性和杀螨活性最高,其对苹果腐烂病菌的抑制率达73.28%,对兔痒螨的致死率达61.55%。【结论】原药别隐品碱十元氮杂环上的羰基被还原成羟基后,不仅提高了其抗菌活性和杀螨活性,同时也拓宽了其抗菌谱。     

甲壳低聚糖体外抗氧化及降血脂活性研究

通过研究甲壳低聚糖对自由基的清除能力和对脂质的吸附效果,探讨其在体外的抗氧化和降血脂活性.试验结果表明,甲壳低聚糖对羟自由基(·OH)和超氧阴离子(O-2·)的清除效果显著,当浓度为30mg·mL-1时,对羟自由基(·OH)和超氧阴离子(O-2·)的清除率分别达到92.9%和97.6%;对脂质的吸附能力也较强,300 ...     

新三唑类化合物的合成及抑菌活性研究

以3,3-二甲基-1-(1,2,4-三唑-1-基)-2-丁酮为原料,合成了6个新化合物,化合物的结构均经1H-NMR和IR予以确认。以小麦赤霉病菌(Fusariumgraminearum)、苹果炭疽病菌(Glomerellacingulata)、玉米大斑病菌(Exserohilumturcium)及南瓜枯萎病菌(Fusariumoxysporium)为供试菌种,在100μg/mL质量浓度下,对合成化合物进行了杀菌活性测定,结果表明6种化合物均有不同程度的杀菌活性。     

苹果多酚的超声波提取及抗氧化作用研究

苹果中富含维生素、矿物质、黄酮类、酚类等多种生物活性物质,具有预防多种疾病的作用,其中原花青素和绿原酸为苹果中主要的酚类物质,且具有很强的抗氧化作用. 该文以国光苹果为试验材料,通过对苹果多酚超声波提取条件的研究,确立了提取的最佳工艺参数,并对苹果多酚的体外抗氧化性进行了研究,采用DPPH法和2-脱氧-D-核糖法研究了苹果多酚对DPPH自由基和·OH自由基的抑制效果. 结果表明,乙醇可作为苹果多酚的良性提取溶剂,其超声波提取的最佳工艺条件:乙醇浓度为60％,料液比为1∶6,提取时间为20 min,提取温度为60℃,提取一次. 苹果多酚清除DPPH自由基速度快,其抗氧化能力可与葡萄籽多酚相媲美. 通过2-脱氧D－核糖法可以看出:在一定浓度范围内,苹果提取物有很强的抗氧化能力,其最佳浓度范围为8～10 mg/mL,此外,苹果提取物及葡萄籽提取物清除羟基自由基（5OH）的效果远远高于茶多酚.