The influence of L-norvalyl-N3-4-methoxyfumaroyl-L-2,3-diaminopropanoic acid, an antifungal agent, on mammalian cells in tissue culture.

Murine leukemia L1210 cells contain active glucosamine 6-phosphate synthase inhibited by N3-4-methoxyfumaroyl-L-2,3-diaminopropanoic acid (FMDP). However, FMDP-peptides do not exhibit any cytotoxicity against these cells, HeLa S3 human cervical carcinoma cells, and LL2 murine Lewis lung carcinoma cells. It is suggested that the lack of cytotoxicity of FMDP-peptides, in spite of good drug uptake and the presence of target enzyme might be due to the poor rate of peptides cleavage by the intracellular peptidases.     

Relationships between stream macroinvertebrates and environmental variables at multiple spatial scales

1. Aquatic communities are structured by multiple forces, and identifying the driving factors over multispatial scales is an important research issue. The East Asian monsoon region is globally one of the richest environments in terms of biodiversity, and is undergoing rapid human development, yet the river ecosystems in this region have not been well studied. We applied a hierarchical framework to incorporate regional and local environmental effects on stream macroinvertebrate communities in this region. The knowledge gained is expected to improve the understanding of the importance of spatial scale on regional and local diversity in the East Asian monsoon region. 2. A national data set of benthic macroinvertebrates and environmental variables (geographical, land‐use, hydrological, substratum and physicochemical elements) in Korean rivers was used to determine the habitat preferences of macroinvertebrates. 3. Latitude, proportion of forest coverage, riffle habitat, silt substratum and temperature were the most important determinants for the ordinations of macroinvertebrate communities in each category evaluated by canonical correspondence analysis (CCA). The optimal habitats for stream macroinvertebrates are not the same for all species, and overall community metrics and abundance of sensitive species tended to be lower in open agricultural and urban streams than in forested streams. The sensitivity of mayflies and stoneflies to anthropogenic disturbances implicated them as good indicators to assess the effects of urban and agricultural activities. 4. A partial CCA was used to evaluate the relative importance of macrohabitat and microhabitat variables on community composition at three spatial scales (whole country, the large Han River basin and two small sub‐basins in the lowlands and highlands). The majority of community variation (17–22% for each environmental element) was explained by macrohabitat variables at the regional spatial scale. In contrast, large proportions (15–18%) were explained by microhabitat variables at the local spatial scale. 5. Our findings indicate that the relative importance of habitat scales should be determined by geographical size and that comprehensive understanding of multispatial scale patterns can be important for implementing sound biodiversity conservation programmes.     

基于质谱技术的蛋白质互作研究进展

蛋白质作为生命活动的执行者,其功能往往体现在与其他蛋白质的相互作用中,研究蛋白-蛋白相互作用对于人们深入了解和预防传染病、靶向治疗多基因疾病、阐明蛋白质的分子作用机制及各种复杂的生命现象具有重要意义。目前,有多种技术被用来研究蛋白间的相互作用,研究难点在于实时捕获瞬时或弱蛋白质间的相互作用,质谱技术（mass spectrometry, MS）可在某种程度上解决该难点。由于质谱技术可研究简单的蛋白质复合物再到大规模的蛋白质组实验,基于质谱技术研究蛋白质间相互作用被越来越多地应用于科学研究中。综述了蛋白质间相互作用检测方法的研究进展,重点介绍了氢氘交换质谱法和化学交联质谱法研究蛋白质间相互作用的优缺点及其应用,最后对基于质谱技术研究蛋白质间相互作用进行了总结与展望,以期为深入开展相关研究提供借鉴。     

LED红、蓝、白组合光对茄子幼苗质量和果皮品质的影响

本试验采用发光二极管(LED)精准调控光源环境,以‘改良大龙茄’为试材,在前期探明红/蓝组合光(R/B)=3/1有利于培育茄子壮苗基础上,以R/B=3/1(9/3,CK₁)和LED白光(W,CK₂)为对照,分别设定LED红蓝白组合光为: R/B/W=3/1/1(9/3/3,T₁)、R/B/W=9/3/8(T₂)、R/B/W=3/1/6(9/3/18,T₃)和R/B/W=3/1/16(9/3/48,T₄),研究其对茄子幼苗生长、根系发育及定植后茄子产量和品质的影响,以期为茄子集约化高效育苗和设施生产补光提供理论依据和技术指导.结果表明: R/B/W=9/3/8组合光处理下,茄子幼苗株高、茎粗、壮苗指数、地上部干重、根干重、根系发育,以及定植后茄皮花青素、类黄酮含量和前期产量均较高;R/B/W=3/1/1组合光处理下,幼苗根冠比、定植后茄皮总酚和果肉中可溶性糖含量较高;而R/B/W=3/1/6组合光处理下,全株叶面积及定植后茄子果肉中游离氨基酸含量较高;R/B/W=3/1/16组合光处理下,定植后茄子果肉中可溶性蛋白含量较高.不同红蓝白组合光可不同程度提高茄子幼苗质量及定植后茄子前期产量和品质,以R/B/W=9/3/8组合光效果最显著.     

依赖于微环境的TGFβ信号

转化生长因子β（transforming growth factor β,TGFβ）家族成员是一类分泌的细胞因子,在胚胎发育、免疫调节、伤口修复、细胞增殖和抑制等过程中发挥重要作用。其中,TGFβ1、TGFβ2和TGFβ3在进化上最晚出现,并以潜伏态分泌。有别于家族中的大多数成员,TGFβ1-3的信号具有时空区域性,并依赖于其所处的微环境。阐明依赖于微环境的TGFβ信号的多层次调控机制对于理解TGFβ信号在免疫、癌症等生理、病理条件下的功能,以及开发临床治疗策略具有重要意义。本文从TGFβ前体复合物的结构入手,并从TGFβ的激活,配体-受体识别,跨膜信号传导及转录调控等方面,论述依赖于微环境的TGFβ信号的调控机制,同时讨论肿瘤微环境中多效的TGFβ信号,进而对今后的研究方向进行展望。     

The CFTR-derived peptides as a model of sequence-specific protein aggregation

Protein aggregation is a hallmark of a growing group of pathologies known as conformational diseases. Although many native or mutated proteins are able to form aggregates, the exact amino acid sequences involved in the process of aggregation are known only in a few cases. Hence, there is a need for different model systems to expand our knowledge in this area. The so-called ag region was previously found to cause the aggregation of the C-terminal fragment of the cystic fibrosis transmembrane conductance regulator (CFTR). To investigate whether this specific amino acid sequence is able to induce protein aggregation irrespective of the amino acid context, we altered its position within the CFTR-derived C-terminal peptide and analyzed the localization of such modified peptides in transfected mammalian cells. Insertion of the ag region into a different amino acid background affected not only the overall level of intracellular protein aggregation, but also the morphology and subcellular localization of aggregates, suggesting that sequences other than the ag region can substantially influence the peptide’s behavior. Also, the introduction of a short dipeptide (His-Arg) motif, a crucial component of the ag region, into different locations within the C-terminus of CFTR lead to changes in the aggregation pattern that were less striking, although still statistically significant. Thus, our results indicate that even subtle alterations within the aggregating peptide can affect many different aspects of the aggregation process.     

FXR激动剂GW4064对裸鼠肝癌细胞移植瘤增殖及血管生成的影响

目的:探讨研究法尼酯x受体(FXR)激动剂GW4064对裸鼠肝癌细胞移植瘤增殖及血管生成的影响。方法:选取人肝癌细胞系Hep G2进行体外培养,将细胞悬液接种于BALB/c裸鼠皮下。裸鼠成瘤后,随机分为两组,分别腹腔注射DMSO和GW4064。一周后,处死动物取肿瘤组织,通过免疫组织化学法检测肿瘤组织中Ki-67和CD31的表达,同时计数肿瘤组织中的微血管密度(CD31-MVD);Western blot法检测其FXR和白介素-8(IL-8)的蛋白表达。结果:与对照组相比,FXR激动剂GW4064处理组的肿瘤组织中FXR的蛋白表达量明显增高,微血管密度CD31-MVD值显著降低,同时Ki-67、IL-8及CD31的表达水平均显著降低。结论:FXR激动剂GW4064能显著增加FXR的表达,抑制裸鼠肝癌细胞移植瘤的增殖及新生血管的形成。     

Discovery of 4-oxo-6-((pyrimidin-2-ylthio)methyl)-4H-pyran-3-yl 4-nitrobenzoate (ML221) as a functional antagonist of the apelin (APJ) receptor

The recently discovered apelin/APJ system has emerged as a critical mediator of cardiovascular homeostasis and is associated with the pathogenesis of cardiovascular disease. A role for apelin/APJ in energy metabolism and gastrointestinal function has also recently emerged. We disclose the discovery and characterization of 4-oxo-6-((pyrimidin-2-ylthio)methyl)-4H-pyran-3-yl 4-nitrobenzoate (ML221), a potent APJ functional antagonist in cell-based assays that is >37-fold selective over the closely related angiotensin II type 1 (AT1) receptor. ML221 was derived from an HTS of the ～330,600 compound MLSMR collection. This antagonist showed no significant binding activity against 29 other GPCRs, except to the κ-opioid and benzodiazepinone receptors (<50/<70%I at 10 μM). The synthetic methodology, development of structure–activity relationship (SAR), and initial in vitro pharmacologic characterization are also presented.     

陆地生态系统碳水通量贡献区评价综述

综述了通量贡献区研究的基本理论、最新进展、研究热点与难点,旨在促进中国区域碳水通量数据空间代表性的定量评价.通量贡献区是通量观测点上风向的空间代表区域,能够反映代表区域对应下垫面的源区内每一点对观测点的通量贡献权重影响,主要受观测高度、空气动力学粗糙度和大气稳定度等因素的影响.通量贡献区通常随着观测高度的增加、空气动力学粗糙度的降低和大气稳定度的增加而变大,反之则变小.通量贡献区的评价模型包括解析模型、拉格朗日随机模型、大涡模拟和闭合模型四类.通量贡献区的评价结果可以广泛应用于通量数据质量评价、实验设计的指导、与遥感技术结合的区域尺度的总初级生产力的估算、城市CO2通量变化的评估以及能量闭合的评价等研究.最新研究表明,对流边界层的通量贡献区存在负的通量贡献区域;有裸地存在的情况下解析模型通常会低估裸地对观测通量的贡献;与水平地面处的通量贡献区相比,山谷处通量贡献区变小而山脊处的通量贡献区变大.通量贡献区模型研究应进一步考虑大气中的平流效应、湍流的非高斯扩散以及建立冠层内部的通量贡献区模型.解决森林冠层内流场的不均匀性、冠层重叠问题、冠层湍流的不稳定性是建立适合冠层内部通量贡献区模型的前提条件.在理想条件的气体释放验证试验的基础上,需要开展复杂条件下的相关试验.     

盐碱胁迫下碱地肤Na+/H+逆向转运蛋白基因KsNHX1表达分析

利用RACE技术得到碱地肤KsNHX1的3’cDNA序列.分子系统进化分析显示,KsNHX1为液泡膜Na⁺/H⁺逆向转运蛋白编码基因.通过半定量RT-PCR检测了该基因在盐碱胁迫下的表达,结果表明: 200 mmol·L^-1 NaCl胁迫2~24 h,KsNHX1在叶片中表达量持续增加;200 mmol·L^-1 NaCl处理10 h,KsNHX1在根、茎、叶和花中的表达都上调;不同浓度NaCl处理下,叶片中KsNHX1表达上调,160 mmol·L^-1时达到最高;低于400 mmol·L^-1浓度下,根中该基因的表达也都上调.经不同浓度Na₂CO₃胁迫,根中KsNHX1的表达变化趋势与相应浓度NaCl胁迫下的变化相同;但叶片中除160 mmol·L^-1 Na₂CO₃处理下KsNHX1表达略有上调外,其他浓度下KsNHX1的表达都低于对照.KsNHX1的表达模式暗示,在不同盐碱胁迫下,碱地肤能够维持体内相对稳定的K⁺/Na⁺,其耐盐特性可能与Na⁺/H⁺逆向转运蛋白的作用密切相关.