Binding Kinetics of ZM241385 Derivatives at the Human Adenosine A2A Receptor

Classical drug design and development rely mostly on affinity‐ or potency‐driven structure–activity relationships (SAR). Thus far, a given compound’s binding kinetics have been largely ignored, the importance of which is now being increasingly recognized. In the present study, we performed an extensive structure–kinetics relationship (SKR) study in addition to a traditional SAR analysis at the adenosine A_2A receptor (A_2AR). The ensemble of 24 A_2AR compounds, all triazolotriazine derivatives resembling the prototypic antagonist ZM241385 (4‐(2‐((7‐amino‐2‐(furan‐2‐yl)‐[1,2,4]triazolo[1,5‐a][1,3,5]triazin‐5‐yl)amino)ethyl)phenol), displayed only minor differences in affinity, although they varied substantially in their dissociation rates from the receptor. We believe that such a combination of SKR and SAR analyses, as we have done with the A_2AR, will have general importance for the superfamily of G protein‐coupled receptors, as it can serve as a new strategy to tailor the interaction between ligand and receptor.     

网络化防空系统研究

网络化防空系统是“网络中心战”与防空作战结合的产物,是防空系统发展的趋势.文中描述了网络化防空系统的优越性,研究了网络化防空系统的体系结构及相关问题,并分析了网络化防空中网络组织结构及指控网、探测网和武器网的协同关系,提出了网络化防空系统中的网络拓扑发现算法和系统体系结构设计方法的基本思路.     

细菌Sh34的鉴定及其对几种植物病原真菌的拮抗作用测定

从黄瓜田土壤中分离得到拮抗细菌Sh34,根据其形态特征和生理生化特性及其细菌的16SrDNA序列分析,鉴定其为枯草芽孢杆菌(Bacillus subtilis)。经平皿测试表明,菌株Sh34及其无菌滤液对黄瓜蔓枯病菌(Ascochyta cucumis)、黄瓜枯萎菌(Fusarium oxysporum f.sp.cucumerinum)、黄瓜菌核((Sclerotinia scleotiorum)、瓜果腐霉菌(Pythium aphanidermatum)、立枯丝核菌(Rhixoctonia solani)等多种植物病原真菌均有良好稳定的抑制作用。其无菌滤液能使黄瓜枯萎菌菌丝老化,原生质浓缩。     

烟草黑胫病拮抗放线菌的分离与筛选

从堆沤过圈肥的土壤中采集样品,用平板法对所采样品进行菌株分离、纯化培养,共获得原始放线菌101株,再通过室内拮抗试验,从随机28株试验菌株中初步获得16株具有一定拮抗作用的菌株。对拮抗效果较好的6株菌株以及抑菌圈较小、但其菌落较大的A15菌株进一步做盆栽防治试验。结果表明,A6的防治效果最好,达到55.26%,其它菌株效果一般。     

Perspectives on additives for polymers. 1. Aspects of stabilization

Since the earliest discovery and subsequent developments in the world of polymers associated problems and increasing applications have resulted in the rapidly expanding field of “additives.” In this context, the term additive is very generalized in that it encompasses many facets associated with ever growing needs. Of the most important are antioxidants (primary and secondary), light stabilizers, processing aids, metal deactivators, flame retardants, biocides, nucleating agents, antistatic compounds, fillers, dyes, pigments (nano, micro, and macro) to name but only a few each serving a particular function and not necessarily all at the same time in the one package. This article presents a general perspective on the type, mode of action, properties, uses, and problems (and circumvention) based on some of the more important key additives. The properties and behavior of many additives in this regard relates very much to the initial incorporation and formulation and in turn is often a major controlling factor in end use performance from a physical, esthetic, structural, mechanical, and chemical point of view. Indeed, with many polymers like PVC, for example, one enters a highly complex world of interactions which can in many cases destroy or even enhance the activity of functional processing additives. Some of these will be highlighted and hopefully the aim being here to enthuse the polymer and additive manufacturers and technologists in the processing laboratories to become more aware of potential issues and problems.     

Auxin/Cytokinin Antagonistic Control of the Shoot/Root Growth Ratio and Its Relevance for Adaptation to Drought and Nutrient Deficiency Stresses

The hormones auxin and cytokinin regulate numerous aspects of plant development and often act as an antagonistic hormone pair. One of the more striking examples of the auxin/cytokinin antagonism involves regulation of the shoot/root growth ratio in which cytokinin promotes shoot and inhibits root growth, whereas auxin does the opposite. Control of the shoot/root growth ratio is essential for the survival of terrestrial plants because it allows growth adaptations to water and mineral nutrient availability in the soil. Because a decrease in shoot growth combined with an increase in root growth leads to survival under drought stress and nutrient limiting conditions, it was not surprising to find that auxin promotes, while cytokinin reduces, drought stress tolerance and nutrient uptake. Recent data show that drought stress and nutrient availability also alter the cytokinin and auxin signaling and biosynthesis pathways and that this stress-induced regulation affects cytokinin and auxin in the opposite manner. These antagonistic effects of cytokinin and auxin suggested that each hormone directly and negatively regulates biosynthesis or signaling of the other. However, a growing body of evidence supports unidirectional regulation, with auxin emerging as the primary regulatory component. This master regulatory role of auxin may not come as a surprise when viewed from an evolutionary perspective.     

药物相互作用动力学分析方法及其 CoDrug 软件

在药物治疗学领域, 复方新药的组方筛选和优化、 临床联合用药方案的设计与评价, 以及中药方剂配伍规律的定量研究, 均需要药物相互作用的动力学分析。 本文结合其专用软件 CoDrug, 简介了多药物联合应用时优选最佳组份、 剂量和比例的权重配方法; 分析药物相互作用动态规律的参数法和映射法, 以及多指标综合分析法; 列出了系统研究药物相互作用动力学的完整方案。     

Selective Extraction of Scandium by a Long Alkyl Chain Carboxylic Acid/Organophosphonic Ester Binary Extractant

ABSTRACT

The organophosphorus extractant 2-ethylhexylphosphonic acid mono-2-ethylhexyl ester (PC88A) is widely used for solvent extraction of rare earth elements in an acidic leaching solution, but stripping of the loaded metals is difficult because of the high affinity between the metals and the extractant. Adding 100 times the concentration of neodecanoic acid (Versatic 10) to the extractant solution reduces the extraction ability for scandium (Sc) and enables quantitative stripping of the loaded Sc with a mild acidic solution, such as a 1 M mineral acid. The loading capacity is dependent on the PC88A concentration, so PC88A is the main species responsible for Sc extraction in the binary mixture. Nuclear magnetic resonance spectroscopy (NMR) of the organic phases suggests a potential interaction between the mixed extractants through the change in the hydrogen bonding. This causes an antagonistic effect and facilitates efficient Sc stripping from the extractant solution, so this method could be used for scandium recovery in industry.     

Structural and Dynamical Insight into PPARγ Antagonism: In Silico Study of the Ligand-Receptor Interactions of Non-Covalent Antagonists

The structural and dynamical properties of the peroxisome proliferator-activated receptor γ (PPARγ) nuclear receptor have been broadly studied in its agonist state but little is known about the key features required for the receptor antagonistic activity. Here we report a series of molecular dynamics (MD) simulations in combination with free energy estimation of the recently discovered class of non-covalent PPARγ antagonists. Their binding modes and dynamical behavior are described in details. Two key interactions have been detected within the cavity between helices H3, H11 and the activation helix H12, as well as with H12. The strength of the ligand-amino acid residues interactions has been analyzed in relation to the specificity of the ligand dynamical and antagonistic features. According to our results, the PPARγ activation helix does not undergo dramatic conformational changes, as seen in other nuclear receptors, but rather perturbations that occur through a significant ligand-induced reshaping of the ligand-receptor and the receptor-coactivator binding pockets. The H12 residue Tyr473 and the charge clamp residue Glu471 play a central role for the receptor transformations. Our results also demonstrate that MD can be a helpful tool for the compound phenotype characterization (full agonists, partial agonists or antagonists) when insufficient experimental data are available.     

劳伦斯与池莉的双性和谐思想之比较

双性和谐是追求男人和女人之间一种完美的两性关系,它是一种理想的文化境界。运用比较方法从两性关系和文化对抗两个视角探讨了劳伦斯和池莉的双性和谐思想。劳伦斯强调的是一种虚幻的双性和谐,其作品主题表现出男权中心主义思想;而池莉则强调现实的双性和谐,其作品主题是以宽容和理解来探讨真正意义上的两性平等。