Identification of the Active Sites in the Methyltransferases of a Transcribing dsRNA Virus

Many double-stranded RNA (dsRNA) viruses are capable of transcribing and capping RNA within a stable icosahedral viral capsid. The turret of turreted dsRNA viruses belonging to the family Reoviridae is formed by five copies of the turret protein, which contains domains with both 7-N-methyltransferase and 2′-O-methyltransferase activities, and serves to catalyze the methylation reactions during RNA capping. Cypovirus of the family Reoviridae provides a good model system for studying the methylation reactions in dsRNA viruses. Here, we present the structure of a transcribing cypovirus to a resolution of ~ 3.8 Å by cryo-electron microscopy. The binding sites for both S-adenosyl-l-methionine and RNA in the two methyltransferases of the turret were identified. Structural analysis of the turret in complex with RNA revealed a pathway through which the RNA molecule reaches the active sites of the two methyltransferases before it is released into the cytoplasm. The pathway shows that RNA capping reactions occur in the active sites of different turret protein monomers, suggesting that RNA capping requires concerted efforts by at least three turret protein monomers. Thus, the turret structure provides novel insights into the precise mechanisms of RNA methylation.     

Pulmonary Toxocariasis Mimicking Invasive Aspergillosis in a Patient with Ulcerative Colitis

A 45-year-old-male who had underlying ulcerative colitis and presented with fever and dry cough. Initially, the patient was considered to have invasive aspergillosis due to a positive galactomannan assay. He was treated with amphotericin B followed by voriconazole. Nevertheless, the patient deteriorated clinically and radiographically. The lung biopsy revealed eosinophilic pneumonia, and ELISA for Toxocara antigen was positive, leading to a diagnosis of pulmonary toxocariasis. After a 10-day treatment course with albendazole and adjunctive steroids, the patient recovered completely without any sequelae. Pulmonary toxocariasis may be considered in patients with subacute or chronic pneumonia unresponsive to antibiotic agents, particularly in cases with eosinophilia.     

萘对川西亚高山森林土壤微生物量、丰度和磷脂脂肪酸的影响

萘作为土壤动物化学抑制剂已在土壤动物生态功能的研究中广泛使用,但其非目标效应使其应用仍存在很大的不确定性。为了解在亚高山森林土壤应用萘抑制土壤动物群落的非目标效应,以川西亚高山森林土壤为研究对象,采用微缩实验研究了土壤微生物生物量、丰度和磷脂脂肪酸对萘胁迫的短期响应。结果表明,萘处理和对照的土壤微生物生物量碳(MBC)、真菌丰度以及细菌、真菌、革兰氏阳性菌(G~+)和革兰氏阴性菌(G~-)PLFAs含量在整个培养期间表现为降低的变化趋势,二者的土壤微生物生物量碳和G~+PLFAs含量以培养52d最低,细菌、真菌和G~-PLFAs含量以培养的45d最低。萘处理和对照的微生物生物量氮(MBN)含量表现出先升高后降低的动态,微生物生物量碳氮比(MBC/MBN)则表现为相反趋势。对照的真菌/细菌PLFAs比值呈现先升高后降低的动态,以培养的17d最高,但萘处理的真菌/细菌PLFAs比值无明显变化规律;萘处理的G~+/G~-PLFAs比值表现为降低的变化趋势,对照的G~+/G~-PLFAs比值表现为先降低后升高的趋势。萘处理仅显著影响了G~+/G~-PLFAs比值,但萘处理和采样时间的交互作用显著影响MBC/MBN、细菌丰度、真菌/细菌丰度比以及细菌、真菌的PLFAs含量、真菌/细菌PLFAs比值、G~+/G~-PLFAs比值。萘作为土壤动物抑制剂对川西亚高山森林土壤微生物群落的非目标效应具有时间变异性。     

Primate stem cells: bridge the translation from basic research to clinic application

A growing body of literature has shown that stem cells are very effective for the treatment of degenerative diseases in rodents but these exciting results have not translated to clinical practice. The difference results from the divergence in genetic, metabolic, and physiological phenotypes between rodents and humans. The high degree of similarity between non-human primates(NHPs) and humans provides the most accurate models for preclinical studies of stem cell therapy. Using a NHP model to understand the following key issues, which cannot be addressed in humans or rodents, will be helpful for extending stem cell applications in the basic science and the clinic. These issues include pluripotency of primate stem cells, the safety and efficiency of stem cell therapy, and transplantation procedures of stem cells suitable for clinical translation. Here we review studies of the above issues in NHPs and current challenges of stem cell applications in both basic science and clinical therapies. We propose that the use of NHP models, in particular combining the serial production and transplantation procedures of stem cells is the most useful for preclinical studies designed to overcome these challenges.     

Optimized syntheses of Fmoc azido amino acids for the preparation of azidopeptides

The rise of CuI‐catalyzed click chemistry has initiated an increased demand for azido and alkyne derivatives of amino acid as precursors for the synthesis of clicked peptides. However, the use of azido and alkyne amino acids in peptide chemistry is complicated by their high cost. For this reason, we investigated the possibility of the in‐house preparation of a set of five Fmoc azido amino acids: β‐azido l ‐alanine and d ‐alanine, γ‐azido l ‐homoalanine, δ‐azido l ‐ornithine and ω‐azido l ‐lysine. We investigated several reaction pathways described in the literature, suggested several improvements and proposed several alternative routes for the synthesis of these compounds in high purity. Here, we demonstrate that multigram quantities of these Fmoc azido amino acids can be prepared within a week or two and at user‐friendly costs. We also incorporated these azido amino acids into several model tripeptides, and we observed the formation of a new elimination product of the azido moiety upon conditions of prolonged couplings with 2‐(1H‐benzotriazol‐1‐yl)‐1,1,3,3‐tetramethyluronium hexafluorophosphate/DIPEA. We hope that our detailed synthetic protocols will inspire some peptide chemists to prepare these Fmoc azido acids in their laboratories and will assist them in avoiding the too extensive costs of azidopeptide syntheses. Experimental procedures and/or analytical data for compounds 3 – 5 , 20 , 25 , 26 , 30 and 43 – 47 are provided in the supporting information. © 2017 The Authors Journal of Peptide Science published by European Peptide Society and John Wiley & Sons Ltd.     

西南地区红花龙胆分布格局模拟与气候变化影响评价

应用最大熵(MaxEnt)模型,基于230条分布记录及33个气候因子数据,模拟全新世中期(约6000年前)、当前时期(1950—2000年)和未来(2050s、2070s)气候条件下,红花龙胆西南地区的潜在分布范围;结合多元统计分析和ArcGIS空间分析,筛选影响物种分布的关键气候因子,探讨不同分布区对气候变化的敏感性.结果表明: 模型训练集AUC值为0.942,验证集AUC值为0.849,表明模型预测的准确性较高.5个气候因子(7月最高气温、8月最低气温、昼夜温差与年温差比值、7月最低气温和6月最低气温)对模型贡献最大,累计贡献率达59.9%.随未来气候变化,红花龙胆适生区将呈现先减少后增加的变化趋势,在RCP 8.5情景下,至2070s阶段,西南地区红花龙胆适宜生境总面积与当前气候条件相比减少15.0%,但云南境内适生区和高适生区面积较当前分别增加32.8%和32.7%.红花龙胆适宜生长于温暖、湿润的气候条件下,气候变暖明显影响着适宜生境的面积和范围,尤其低海拔分布区对气候变化较敏感,适宜生境退缩严重,而高海拔地区由于降水、温度条件的改善适宜生境有所增加.随着全球气候的变化,未来西南地区红花龙胆主要分布区可能向西迁移,并向更高海拔扩张.     

长白山阔叶红松林3个常见树种径向生长的影响因素

为探究树木径向生长的影响因子,基于对长白山阔叶红松林25 hm²样地中3个常见树种红松、紫椴、蒙古栎连续5年的生长环监测数据,分析各树种的季节生长变化,比较树种间的生长速率差异,并分析初始径级、邻体树木竞争、土壤、地形因素等对不同树种径向生长的作用.结果表明: 3个树种径向生长的季节变化趋势一致,树木于5月末开始生长,7月是生长旺盛期,8月底生长开始减缓,于10月中下旬停止生长.3个树种的径向相对生长率存在显著差异,蒙古栎相对径向生长率显著高于红松和紫椴,该差异在小、中径级个体中表现更为显著.3个树种径向生长的主要影响因子不同,邻体树木的竞争显著抑制了红松和蒙古栎的径向生长,而紫椴的径向生长主要受初始径级、土壤和地形等因子的影响.