Synthesis and DNA-recognition and -cleavage properties of multiply charged porphyrin esters

A series of systematically modified porphyrin esters, compounds 1-6, with multiple, permanent positive charges introduced at the meso-positions via N-methylated 4-, 3-, or 2-pyridyl moieties, were prepared and characterized. Their singlet-oxygen production, CT-DNA-binding properties, and plasmid-DNA photocleavage propensities were determined spectroscopically and by gel electrophoresis, and compared to those of the known, fourfold-charged parent porphyrin 4,4',4',4'-porphyrin-5,10,15,20-tetrayltetrakis(1-methylpyridinium) (TMPyP4). Some interesting structure-activity relationships could be established to rationalize effects affecting DNA binding mode and cleavage ability.     

Pre-Existing HCV Variants Resistant to DAAs and Their Sensitivity to PegIFN/RBV in Chinese HCV Genotype 1b Patients

BackgroundThe efficacy of direct-acting antiviral agents (DAAs) could be attenuated by the presence of resistance-associated variants (RAVs). The aim of this study was to investigate the natural prevalence of RAVs among Chinese HCV genotype 1b patients and analyze the efficacy of pegylated interferon (PegIFN)/ribavirin (RBV) therapy in patients with and without RAVs at baseline.MethodsDirect sequencing of the HCV NS3, NS5A and NS5B regions was performed in baseline serum samples of 117 DAAs-naïve subjects infected with HCV genotype 1b. The efficacy of PegIFN/RBV therapy in patients with and without RAVs at baseline was analyzed by comparing the response rates between patients with RAVs and patients with wild type virus.ResultsThe incidence of RAVs was 8.00% (8/100) in the NS3 region (T54S, n = 1, 1.00%; R117H, n = 5, 5.00%; S122T, n = 1, 1.00%; S174F, n = 1, 1.00%), 29.91% (32/107) in the NS5A region (L28M, n = 12, 11.21%; R30Q, n = 10, 9.35%; L31M, n = 1, 0.93%; P58S, n = 4, 3.74%; Y93H, n = 8, 7.48%) and 98.15% (106/108) in the NS5B region (L159F, n = 1, 0.93%; C316N, n = 103, 95.37%; A421V, n = 6, 5.56%). The response rates to PegIFN/RBV treatment did not differ between patients with or without RAVs in the NS5A region.ConclusionsPre-existing RAVs, including key RAVs, were detected in Chinese DAAs-naïve patients infected with HCV genotype 1b. IFN-based therapy could be a good option for patients with RAVs, especially key RAVs, at baseline.     

天童常绿阔叶林中常绿与落叶物种的物种多度分布格局

物种多度分布是对群落内不同物种多度情况的数量描述, 作为理解群落性质的基石, 其形成机制受到广泛关注。常绿与落叶物种是两类有着不同物候性状与生长策略的物种集合, 它们普遍共存于常绿阔叶林中。在天童20 ha常绿阔叶林动态监测样地内, 虽然常绿物种在物种多度和胸高断面积等指标上占有绝对优势, 但其在物种丰富度上却不及落叶物种。分析两者在常绿阔叶林中的物种多度分布特征, 能够为理解常绿阔叶林内物种多样性的维持机制提供一个全新的视角。为此, 我们基于天童样地的植被调查数据, 一方面利用累积经验分布函数对两类生活型植物的物种多度分布进行描述, 使用Kolmogorov-Smirnov检验(K-S检验)判断其差异性; 另一方面, 采用纯统计模型、生态位模型和中性理论模型对二者的物种多度分布曲线进行拟合, 并基于K-S检验的结果以及AIC值进行最优模型的筛选。结果显示: (1)常绿与落叶物种的物种多度分布曲线间并无显著差异。(2)在选用的3类模型中, 中性理论模型对于两类物种多度分布曲线的拟合效果都最好, 而生态位模型的拟合效果则一般。从上述结果可以看出, 尽管常绿与落叶物种在物种数量和多度等方面均存在差异, 但它们却有着近似的物种多度分布格局以及相近的多样性维持机制。然而, 鉴于模型拟合的结果只能作为理解群落多样性构建机制的必要非充分条件, 故而只能初步判定中性过程对于常绿与落叶物种的物种多样性格局影响更大, 却不能排除或衡量诸如生态位分化等其他过程在两类生活型多样性格局形成中的贡献。     

The Streptomyces coelicolor Lipoate-protein Ligase Is a Circularly Permuted Version of the Escherichia coli Enzyme Composed of Discrete Interacting Domains

Lipoate-protein ligases are used to scavenge lipoic acid from the environment and attach the coenzyme to its cognate proteins, which are generally the E2 components of the 2-oxoacid dehydrogenases. The enzymes use ATP to activate lipoate to its adenylate, lipoyl-AMP, which remains tightly bound in the active site. This mixed anhydride is attacked by the ϵ-amino group of a specific lysine present on a highly conserved acceptor protein domain, resulting in the amide-linked coenzyme. The Streptomyces coelicolor genome encodes only a single putative lipoate ligase. However, this protein had only low sequence identity (<25%) to the lipoate ligases of demonstrated activity and appears to be a circularly permuted version of the known lipoate ligase proteins in that the canonical C-terminal domain seems to have been transposed to the N terminus. We tested the activity of this protein both by in vivo complementation of an Escherichia coli ligase-deficient strain and by in vitro assays. Moreover, when the domains were rearranged into a protein that mimicked the arrangement found in the canonical lipoate ligases, the enzyme retained complementation activity. Finally, when the two domains were separated into two proteins, both domain-containing proteins were required for complementation and catalysis of the overall ligase reaction in vitro. However, only the large domain-containing protein was required for transfer of lipoate from the lipoyl-AMP intermediate to the acceptor proteins, whereas both domain-containing proteins were required to form lipoyl-AMP.     

Molecular Typing of Pathogenic Leptospira Serogroup Icterohaemorrhagiae Strains Circulating in China during the Past 50 Years

Background

Leptospirosis is one of the most important neglected tropical infectious diseases worldwide. Icterohaemorrhagiae has been throughout recent history, and still is, the predominant serogroup of this pathogen in China. However, very little in detail is known about the serovars or genotypes of this serogroup.

Methodology/Principal Findings

In this study, 120 epidemic strains from five geographically diverse regions in China collected over a 50 year period (1958~2008), and 8 international reference strains characterized by 16S rRNA sequencing and MLST analysis. 115, 11 and 2 strains were identified as L. interrogans, L. borgpetersenii, and L. kirschneri, respectively. 17 different STs were identified including 69 ST1 strains, 18 ST17, 18 ST128, 9 ST143 and 2 ST209. The remaining 12 strains belonged to 12 different STs. eBURST analysis demonstrated that, among the clonal complexes isolated (CCs), CC1 accounted for 73.3% (88/120) strains representing three STs: ST1, ST128 and ST98. ST1 was the most likely ancestral strain of this CC, followed by singleton CC17 (17/120) and CC143 (11/120). Further analysis of adding 116 serogroup Icterohaemorrhagiae strains in the MLST database and studies previously described using global eBURST analysis and MST dendrogram revealed relatively similar ST clustering patterns with five main CCs and 8 singletons among these 244 strains. CC17 was found to be the most prevalent clone of pathogenic Leptospira circulating worldwide. This is the first time, to our knowledge, that ST1 and ST17 strains were distributed among 4 distinct serovars, indicating a highly complicated relationship between serovars and STs.

Conclusions/Significance

Our studies demonstrated a high level of genetic diversity in the serogroup Icterohaemorrhagiae strains. Distinct from ST17 or ST37 circulating elsewhere, ST1 included in CC1, has over the past 50 years or so, proven to be the most prevalent ST of pathogenic leptospires isolated in China. Moreover, the complicated relationship between STs and serovars indicates an urgent need to develop an improved scheme for Leptospira serotyping.     

The Ecological Secondary Xylem Anatomy of 7 Desert Species of Leguminosae

The wood anatomy of 7 species (Ammopiptanthus mongolicus, Amorpha fruticosa, Halimodendron halodendron, Hedysarum mongolicum. Hedysarum scoparium, Lespedeza bicolor and Robinia pseudoacacia)of Leguminosae, which grow in desert regions of Northern China, is described in details. A comparative study on the quantitative wood anatomical characters among the species is made. Except some anatomical characters in A. fruticosa were larger in vessel diameter, thin walled in vessels and libriform fibres, all the rest six species showed a general similarities:vessel frequency/sq, mm very numerous and percentage of multiple vessels high; vessel elements very short, perforations simple and in almost horizontal end walls, intervessel bordered pits alternate and vestured; libriform fibres very short, and usually with thickened walls, and with simple pits; average ray height very low, and with multiseriate as well as uniseriate. However, there are differences in other characters, e. g. vessel distribution, percentage of solitary vessels; spiral thickenings present or absent; amount of axial parenchyma and distribution; ray frequency and type; crystals present or absent, and crystal distribution, if present. According to these anatomical diversities, a key to the identification of the 7 species is given. In this article, the relation between the structure of wood and the environmental influences has been discussed.     

中国蝴蝶新种, 新亚种及新记录种（Ⅲ）（鳞翅目）

记述中国粉蝶科1新种,4新亚种,1新型,1中国新记录种及6个《中国蝶类志》未记述的已知种,所有模式标本保存在西北农林科技大学昆虫博物馆。     

Ion Specificity of Na+-Transporting Systems in the Plasma Membrane of the Halotolerant Alga Tetraselmis (Platymonas) viridis

Vesicular preparations of plasma membranes (PM) from the microalga Tetraselmis (Platymonas) viridisRouch were used to investigate the ion specificity of the Na⁺/H⁺antiporter and Na⁺-translocating ATPase, two Na⁺-transporting systems previously identified functionally by our studies of T. viridisPM. The Na⁺/H⁺antiporter and Na⁺-ATPase were shown to translocate, with similar efficiencies, Na⁺and Li⁺across the membrane, whereas other cations, such as K⁺, Rb⁺, and Cs⁺, were not transported by these systems. Transport of the latter cations across PM of T. viridisoccurred through the ion channels of PM, which were apparently selective for K⁺.     

Endogenous angiogenesis inhibitors and their therapeutic implications

A number of endogenous inhibitors targeting the tumor vasculature have recently been identified using in vitro and in vivo antiangiogenesis models. While many of these angiogenesis inhibitors display a broad spectrum of biological actions on several systems in the body, several inhibitors including angiostatin, endostatin, and serpin antithrombin seem to act specifically on the proliferating endothelial cell compartment of the newly formed blood vessels. The discovery of these specific endothelial inhibitors not only increases our understanding of the functions of these molecules in the regulation of physiological and pathological angiogenesis, but may also provide an important therapeutic strategy for the treatment of cancer and other angiogenesis dependent diseases, including diabetic retinopathy and chronic inflammations. Systemic administration of these angiogenesis inhibitors in animals significantly suppresses the growth of a variety of tumors and their metastases. However, their production as functional recombinant proteins has been proven to be difficult. In addition, high dosages of these inhibitors are required to suppress tumor growth in animal studies. Other disadvantages of the antiangiogenic protein therapy include repeated injections, prolonged treatment, transmission of toxins and infectious particles, and high cost for manufacturing large amounts of protein molecules. Thus, alternative strategies need to be developed in order to improve the clinical settings of antiangiogenic therapy. Developments of these strategies are ongoing and they include identification of more potent inhibitors, antiangiogenic gene therapy, improvement of protein/compound half-lives in the circulation, increase of their concentrations at the disease location, and combinatorial therapies with approaches including chemotherapy, radiotherapy, and immunotherapy. Despite the above-mentioned disadvantages, a few inhibitors have entered into the early stages of clinical trials and they may bring new hopes for the treatment of cancer and other angiogenesis dependent diseases.