-cyano-substituted analogoues of decarboxylated S-adenosylmethionine as enzyme activated, irreversible inhibitors of S-adenosylmethionine decarboxylase

A pair of -cyano analogues of decarboxylated S-adenosylmethionine (2a and 2b) were synthesized as potential enzyme activated, irreversible inhibitors of the[pyruvoyl enzyme S-adenosylmethionine decarboxylase (AdoMet-DC). Each of these analogues acts as an irreversible inactivator for ADoMet-DC from Escherichia coli (IC₅₀ values of 9 and 50 μM, respectively). These analogues also inactivate human AdoMet-DC, with K_I values of 246.6 and 7.2 μM, and k_inact values of 0.29 and 0.03 min⁻¹, respectively.     

论Paracarinachitids

研究证明Paracarinachitids的外骨骼都不是由8个骨板组成,骨片具有清楚的微层构造,表明它们是由叠覆的生长层组成,每个生长节上有一个小刺,在顶端下侧面前端都有肾形缺凹。同一标本上存在顶端部的融合和远顶端部的分节彼此递交的现象表明这种表象上的差异是后期次生磷灰石包裹或腐蚀的结果;其下侧缘融合和下侧面无缝隙的现象说明将Paracarinachites spinus的骨片分成头板、中间板和尾板是没有根据的。骨片表面存在的针状体是成岩作用的产物,它是粘土矿物和磷酸盐针状结晶体而不是多板纲的骨针。凡此强有力地说明Yangtzechiton是Paracarinachites的晚出同义名。根据形态功能、组织结构,特别是叠覆状排列的骨片和孤立的生长节等特征,paracarinachitids 可能与zhijinitids有密切关系,但两者是否同源尚缺少进一步的证据、据此,笔者认为将paracarinachitids 暂置于分类位置未定的具骨片后生动物较妥。     

Preparation of the pure diastereomeric forms of S- (5′-deoxy-5′-adenosyl)-1-ammonio-4-methylsulfonio-2- cyclopentene and their evaluation as irreversible inhibitors of S-adenosylmethionine decarboxylase from Escherichia coli

The conformationally restricted S-adenosylmethionine analogue AdoMac (S-(5′-deoxy-5′-adenosyl)-1-ammonio-4-methylsulfonio-2-cyclopentene has been shown to act as an enzyme activated, irreversible inhibitor of theEscherichia coli form of the enzyme S-adenosylmethionine decarboxylase. Inactivation of the enzyme is presumably initiated by formation of an imine linkage between the inhibitor and the terminal pyruvate of the enzyme, followed by base-catalyzed elimination of methylthioadenosine and generation of a latent electrophile. Removal of the driving force for the elimination of methylthioadenosine resulted in a reversibly binding inhibitor. Thus, the thioether analogue corresponding to AdoMac, and the corresponding dihydro derivative (H₂-AdoMac), reversibly inhibit the enzyme. AdoMac was resolved into its four pure diastereomeric forms, and each diastereomer was evaluated as an irreversible inhibitor of the enzyme. The K_I values for the individual diastereomers range between 3.83 and 39.6 μM, with the cis-1S,4R diastereomer being the most potent inhibitor. However, the k_inact values for the four diastereomers are not significantly different, suggesting that the binding of each diastereomer to the enzyme is configuration-dependent, while the subsequent inactivation likely proceeds through a single intermediate which is formed from each of the four diastereomers. Since each pure diastereomer represents a distinct conformational mimic exhibiting restricted sidechain rotation, the data suggests that these and related analogues may be useful as conformational probes for the catalytic site of AdoMet-DC.     

Nonparametric and semiparametric estimation with sequentially truncated survival data

In observational cohort studies with complex sampling schemes, truncation arises when the time to event of interest is observed only when it falls below or exceeds another random time, that is, the truncation time. In more complex settings, observation may require a particular ordering of event times; we refer to this as sequential truncation. Estimators of the event time distribution have been developed for simple left-truncated or right-truncated data. However, these estimators may be inconsistent under sequential truncation. We propose nonparametric and semiparametric maximum likelihood estimators for the distribution of the event time of interest in the presence of sequential truncation, under two truncation models. We show the equivalence of an inverse probability weighted estimator and a product limit estimator under one of these models. We study the large sample properties of the proposed estimators and derive their asymptotic variance estimators. We evaluate the proposed methods through simulation studies and apply the methods to an Alzheimer's disease study. We have developed an R package, seqTrun , for implementation of our method.     

LEP and LEPR are possibly a double-edged sword for wound healing

Wound healing is a complex and error-prone process. Wound healing in adults often leads to the formation of scars, a type of fibrotic tissue that lacks skin appendages. Hypertrophic scars and keloids can also form when the wound-healing process goes wrong. Leptin (Lep) and leptin receptors (LepRs) have recently been shown to affect multiple stages of wound healing. This effect, however, is paradoxical for scarless wound healing. On the one hand, Lep exerts pro-inflammatory and profibrotic effects; on the other hand, Lep can regulate hair follicle growth. This paper summarises the role of Lep and LepRs on cells in different stages of wound healing, briefly introduces the process of wound healing and Lep and LepRs, and examines the possibility of promoting scarless wound healing through spatiotemporal, systemic, and local regulation of Lep levels and the binding of Lep and LepRs.     

Molecular mimicry in Lyme disease: monoclonal antibody H9724 to b. burgdorferi flagellin specifically detects chaperonin-HSP60

A monoclonal antibody (H9724), specific for the 41-kDa flagellar protein of the Lyme disease pathogen Borrelia burgdorferi, cross-reacts with human axons and detects one major protein in human neuroblastoma cell extracts. The homologous cross-reacting protein has now been isolated from calf adrenal and identified as chaperonin-HSP60 by N-terminal sequencing.     

盐磷胁迫对木麻黄和台湾相思种子萌发及幼苗生长的影响

恶劣环境下,人工海防林因面临养分胁迫而经营困难。为探讨盐、磷胁迫对主要海防林树种木麻黄和台湾相思种子萌发及生长的影响,该研究分别用不同浓度的NaCl(盐)和KH₂PO₄(磷)溶液处理种子和浇灌幼苗,测定种子萌发和幼苗生长指标。结果表明：(1)高盐胁迫显著抑制种子萌发,对幼苗生长有一定影响,但两种植物影响程度不同;台湾相思种子萌发耐盐性高于木麻黄,前者相对盐害率最大值为23.03%,后者为89.15%;随着盐浓度增加,木麻黄和台湾相思种子的发芽率、发芽势、发芽指数和活力指数均降低,对应最大值分别为38.70%、34.67%、18.70、0.055和76.67%、62.22%、48.46、6.11。(2)两种植物的株高和根长随盐浓度增加而降低,木麻黄和台湾相思株高分别为12.29～6.01 mm和48.27～17.33 mm,根长分别为8.57～1.45 mm和33.41～5.88 mm;台湾相思根、茎、叶生物量及根冠比均随盐浓度的增加逐渐减小,木麻黄各处理差异较小。(3)台湾相思的种子和幼苗较木麻黄更耐低磷环境,二者最适磷浓度存在差异;木麻黄种...     

植物多基因干扰载体体系构建与效用分析

多数重要的功能基因属于多基因家族,这些家族成员间存在功能冗余,高效的多基因干扰体系对研究多基因家族成员的生物学功能及其分子调控机制具有重要意义。对pCAMBIA1301载体改造,构建了适用于植物的多基因干扰体系pCAMBIA1301m和pCAMBIA1301s。使用该多基因干扰体系构建了四基因的干扰载体pCAMBIA1301m：35S∷SlPP2C1-2-3-4,4个目标基因为来源于番茄PP2C家族A组的PP2C1、PP2C2、PP2C3和PP2C4,并通过遗传转化导入番茄,用GUS染色和PCR检测转基因阳性植株,再利用RT-qPCR技术检测T₁和T₂代转基因植株中目标基因的干扰效率,用T₂代种子分析转基因番茄对ABA敏感性。结果表明,应用该干扰体系成功获得了四基因干扰的转基因植株35S∷SlPP2C1-2-3-4。在转基因番茄中4个目标基因的表达量显著低于野生型,其干扰效率均高于70%,转基因番茄种子萌发具有强烈的ABA不敏感性。多基因干扰体系能高效地同时沉默多个目标基因。     

植物水分来源稳定氢氧同位素偏移研究进展

稳定氢氧同位素技术能有效计算植物根系水分吸收量,确定植物水分来源贡献,评估植物水分利用策略,是生态水文学探究大气-植被-土壤系统水分传输过程机制的有效工具。然而土壤与木质部水稳定氢氧同位素比值(δ²H和δ¹⁸O)偏移造成植物水分来源贡献率计算偏差,引起氢氧同位素结果差异的原因尚不明晰。该文首先简要介绍氢氧稳定同位素比值偏移现象,其次沿水分在土壤-植物-大气连续体中的传输路径构建梳理框架,系统阐述了3个界面(植物-大气界面、土壤-大气界面和根系-土壤界面)与2个空间(植物体和土壤层)中引起δ²H与δ¹⁸O偏移的自然效应,同时概述了土壤与木质部样品提取与测定技术中引起δ²H与δ¹⁸O偏差的人为效应。最后,根据现有研究进展提出主要问题,从获取同位素时空数据,微尺度同位素偏移原因,提取与测定技术的优化三方面指出未来的发展方向。