Reactivation of mutant p53: Constraints on mechanism highlighted by principal component analysis of the DNA binding domain

Most p53 mutations associated with cancer are located in its DNA binding domain (DBD). Many structures (X‐ray and NMR) of this domain are available in the protein data bank (PDB) and a vast conformational heterogeneity characterizes the various free and complexed states. The major difference between the apo and the holo‐complexed states appears to lie in the L1 loop. In particular, the conformations of this loop appear to depend intimately on the sequence of DNA to which it binds. This conclusion builds upon recent observations that implicate the tetramerization and the C‐terminal domains (respectively TD and Cter) in DNA binding specificity. Detailed PCA analysis of the most recent collection of DBD structures from the PDB have been carried out. In contrast to recommendations that small molecules/drugs stabilize the flexible L1 loop to rescue mutant p53, our study highlights a need to retain the flexibility of the p53 DNA binding surface (DBS). It is the adaptability of this region that enables p53 to engage in the diverse interactions responsible for its functionality. Proteins 2016; 84:1443–1461. © 2016 Wiley Periodicals, Inc.     

Identification of the active site of human mitochondrial malonyl‐coenzyme a decarboxylase: A combined computational study

Malonyl‐CoA decarboxylase (MCD) can control the level of malonyl‐CoA in cell through the decarboxylation of malonyl‐CoA to acetyl‐CoA, and plays an essential role in regulating fatty acid metabolism, thus it is a potential target for drug discovery. However, the interactions of MCD with CoA derivatives are not well understood owing to unavailable crystal structure with a complete occupancy in the active site. To identify the active site of MCD, molecular docking and molecular dynamics simulations were performed to explore the interactions of human mitochondrial MCD (HmMCD) and CoA derivatives. The findings reveal that the active site of HmMCD indeed resides in the prominent groove which resembles that of CurA. However, the binding modes are slightly different from the one observed in CurA due to the occupancy of the side chain of Lys183 from the N‐terminal helical domain instead of the adenine ring of CoA. The residues 300 ? 305 play an essential role in maintaining the stability of complex mainly through hydrogen bond interactions with the pyrophosphate moiety of acetyl‐CoA. Principle component analysis elucidates the conformational distribution and dominant concerted motions of HmMCD. MM_PBSA calculations present the crucial residues and the major driving force responsible for the binding of acetyl‐CoA. These results provide useful information for understanding the interactions of HmMCD with CoA derivatives. Proteins 2016; 84:792–802. © 2016 Wiley Periodicals, Inc.     

蜜柚不同砧穗组合苗期嫁接亲和性评价

为评价蜜柚砧穗的嫁接亲和性,以红绵蜜柚(Citrus grandis‘Hongmianmiyou’)、三红蜜柚(‘Sanhongmiyou’)、红肉蜜柚(‘Hongroumiyou’)、黄金蜜柚(‘Huangjinmiyou’)和琯溪蜜柚(‘Guanximiyou’)作接穗,枳(Poncirus trifoliata)、香橙(Citrus junos)、酸柚(Citrus grandis)作砧木,田间调查15个砧穗组合苗期生长指标,测定嫁接愈合期叶片多酚氧化酶(PPO)和过氧化物酶(POD)活性、可溶性蛋白和可溶性糖含量,采用主成分分析和聚类分析方法对蜜柚砧穗组合嫁接亲和性进行评价。结果表明,以柚作砧木的砧穗组合保存率高、生长势旺盛、抽梢能力强,以枳和香橙作砧木的砧穗组合部分指标存在差异,其中红绵蜜柚和黄金蜜柚以枳作砧木时表现出不亲和现象。不同砧穗组合嫁接愈合时期PPO、POD、可溶性蛋白和可溶性糖变化趋势基本一致。主成分分析结果表明,4个主成分基本反映了15个指标91.33%的数据信息。聚类分析将15个砧穗组合分为4类,与主成分分析结果基本一致。因此,琯溪蜜柚、红肉蜜柚和三红蜜柚嫁接可采用枳和柚作砧木,红绵蜜柚和黄金蜜柚嫁接可采用柚作砧木,红绵蜜柚和黄金蜜柚嫁接不可采用枳作砧木。     

红外光谱结合多元统计方法的不同产地红根草红外指纹图谱比较研究

红根草为唇形科鼠尾带根全草植物,是著名的广西道地药材和常用中药,对白血病细胞有很强的抑制作用,同时具有较强的抗菌活性和抗癌作用,主治菌莉、腹泻、肠炎、肺炎、急性咽喉炎、扁桃体炎、感冒等症。为快速鉴别和评价不同产地中药红根草主要化学成分的差异,该研究利用红外光谱对不同产地红根草进行检测,并结合主成分分析和聚类分析及载荷因子等方法对不同产地样本进行鉴别。结果表明：(1)在1800~600 cm-1范围内,不同产地红根草根系在1727、1635、1551、1513、1442、1373、1255、1154、1036、795、776、690 cm-1等处均有较强的振动吸收,表明不同产地红根草主要化学组分构成比较相似。(2)红外指纹图谱结合主成分和聚类分析结果表明,不同产地红根草化学成分的差异与地理位置有明显对应性,产地相近的地区红根草化学成分的较似,产地较远的区域红根草化学成分差异较大,但两种方法检测结果均有自己的特征。(3)通过PCA载荷因子分析,可以得出比原始图谱更多的化学成分信息,对主成分聚类贡献较大的吸收峰主要表现在1670、1630、1616、1579、1473、1411、1159、1129、1082、1042、1000、972、946、913、891、806 cm-1附近,进一步揭示出不同产地红根草化学成分差异主要是红根草内酯和甾醇类成分,以及主要有效成分红根草邻醌和丹参酮类成分的差异。该研究结果为红根草的引种栽培及良种选育研究提供了参考。     

石灰岩山地优势种淡竹生物量分配的影响主因研究

该研究在江西省瑞昌市设置9个淡竹林样地,调查和测定了淡竹林密度、淡竹各构件的生物量和总生物量,以及土壤含水率、土层厚度、林下裸岩率、pH、电导率、全氮和全磷等7个土壤环境因子,并对竹林密度、土壤环境因子和淡竹生物量分配指标进行了相关分析和回归分析。结果表明：(1)密度与淡竹蔸比重相关系数r达0.66( P＝0.02<0.05),而与叶比重、枝比重、秆比重、鞭比重、根比重及根冠比均无显著相关关系;土壤环境因子与生物量分配指标有密切相关,环境主成分Z1与叶比重、秆比重及蔸比重均显著相关(P<0.05),Z2与鞭比重显著相关(P＝0.034<0.05)。(2)密度与土壤环境因子密切相关(P<0.05),控制土壤环境因子的偏相关分析显示密度与淡竹生物量分配不显著相关( P>0.05),而控制密度时,土壤环境因子与淡竹生物量分配仍有显著相关关系(P<0.05);逐步回归分析也验证了偏相关分析的结果,密度被排除出回归方程。分析认为,土壤含水率、土层厚度及土壤养分等环境因子是影响石灰岩山地优势种淡竹生物量分配的主因,密度对生物量分配的影响实为土壤环境因子的间接作用。该研究结果为石灰岩地区植被恢复提供了理论支撑。     

A New Type of Anatolian Propolis: Evaluation of Its Chemical Composition,Activity Profile and Botanical Origin

This study was undertaken to analyze the phenolic profiles of 19 propolis samples from Turkey by using a high‐performance thin‐layer chromatographic (HPTLC) method in order to identify their plant origins. Furthermore, their antioxidant and antimicrobial activity profiles were comparatively evaluated. For the appraisal of antioxidant potential, total phenolic (TPC) and total flavonoid contents (TFC) of propolis samples were firstly determined and then their effects on free radicals were evaluated by FRAP, ABTS^.+, CUPRAC, DPPH^. and HPTLC‐DPPH^. methods. Antimicrobial activity of propolis samples against Staphylococcus aureus (ATCC 6538), Pseudomonas aeruginosa (ATCC 15442), Escherichia coli (ATCC 11229) and Candida albicans ATCC 10231 were determined by disc diffusion and broth dilution methods. HPTLC fingerprinting analyses revealed that O‐type (botanical origin from Populus nigra L.) was the primarily available propolis type in Turkey. Moreover, 3‐O‐methylquercetin (3MQ) rich propolis was identified as a new propolis type for the first time. Principal component analysis (PCA) indicated that 3MQ‐type propolis differs from the O‐type. Antioxidant activity studies showed that O‐type of propolis possesses higher antioxidant effect than the other tested propolis types. Quercetin, caffeic acid, caffeic acid phenethyl ester (CAPE) and galangin were determined to contribute significantly to the antioxidant potential of O‐type propolis among others. Propolis extracts exerted moderate antimicrobial activity against the tested microorganisms with MIC values between the ranges of 128–512 μg/mL.     

Gene editing of the wheat homologs of TONNEAU1‐recruiting motif encoding gene affects grain shape and weight in wheat

Grain size and weight are important components of a suite of yield‐related traits in crops. Here, we showed that the CRISPR‐Cas9 gene editing of TaGW7, a homolog of rice OsGW7 encoding a TONNEAU1‐recruiting motif (TRM) protein, affects grain shape and weight in allohexaploid wheat. By editing the TaGW7 homoeologs in the B and D genomes, we showed that mutations in either of the two or both genomes increased the grain width and weight but reduced the grain length. The effect sizes of mutations in the TaGW7 gene homoeologs coincided with the relative levels of their expression in the B and D genomes. The effects of gene editing on grain morphology and weight traits were dosage dependent with the double‐copy mutant showing larger effect than the respective single copy mutants. The TaGW7‐centered gene co‐expression network indicated that this gene is involved in the pathways regulating cell division and organ growth, also confirmed by the cellular co‐localization of TaGW7 with α‐ and β‐tubulin proteins, the building blocks of microtubule arrays. The analyses of exome capture data in tetraploid domesticated and wild emmer, and hexaploid wheat revealed the loss of diversity around TaGW7‐associated with domestication selection, suggesting that TaGW7 is likely to play an important role in the evolution of yield component traits in wheat. Our study showed how integrating CRISPR‐Cas9 system with cross‐species comparison can help to uncover the function of a gene fixed in wheat for allelic variants targeted by domestication selection and select targets for engineering new gene variants for crop improvement.     

基于Nextflow构建的宏条形码自动化分析流程EPPS

基于宏条形码技术的物种快速检测有助于生物多样性的评估、预测和保护。本文介绍了常用宏条形码分析的步骤和参数设定方法。我们利用Nextflow搭建了一款宏条形码分析流程EPPS, 可以自动化地运行从原始数据的质量控制到环境多样性的比较。Nextflow软件还拥有流程监控的功能, 可视化输出每个进程所消耗的时间与内存。本文还使用测试数据和已发表数据证明该平台能够有效地分析宏条形码数据并可靠地分析环境生物多样性的相似性。     

橄榄果实发育过程中细胞壁物质和相关酶活性变化

为了解橄榄(Canarium album)果实质地差异形成的原因,以鲜食型橄榄‘清榄1号’和加工型橄榄‘长营’为材料,对果实发育过程中细胞壁物质含量和相关酶活性进行了测定。结果表明,随着橄榄果实的成熟,‘清榄1号’较‘长营’维持较高的果胶甲酯酶(PME)活性,促进了果胶的水解,离子型果胶(ISP)含量较高而共价型果胶(CSP)含量较低。2个橄榄品种纤维素含量均较高,‘清榄1号’果实的半纤维素含量低于‘长营’。‘清榄1号’木质素含量低于‘长营’,较高的苯丙氨酸解氨酶(PAL)和过氧化物酶(POD)活性促进了木质素含量的增加。因此,ISP、CSP、半纤维素和木质素含量的不同可能是2个橄榄品种果实质地差异形成的原因。