Conjugation of phosphonoacetic acid to nucleobase promotes a mechanism-based inhibition

Small molecule inhibitors have a powerful blocking action on viral polymerases. The bioavailability of the inhibitor, nevertheless, often raise a significant selectivity constraint and may substantially limit the efficacy of therapy. Phosphonoacetic acid has long been known to possess a restricted potential to block DNA biosynthesis. In order to achieve a better affinity, this compound has been linked with natural nucleotide at different positions. The structural context of the resulted conjugates has been found to be crucial for the acquisition by DNA polymerases. We show that nucleobase-conjugated phosphonoacetic acid is being accepted, but this alters the processivity of DNA polymerases. The data presented here not only provide a mechanistic rationale for a switch in the mode of DNA synthesis, but also highlight the nucleobase-targeted nucleotide functionalization as a route for enhancing the specificity of small molecule inhibitors.     

Translocation of phosphatidylthreonine and -serine to mitochondria diminishes exponentially with increasing molecular hydrophobicity

Some cultured cells contain significant amounts of a rarely recognized phospholipid, phosphatidylthreonine. Since phosphatidylthreonine is a structural analog of phosphatidylserine, the question rises whether it is transported to mitochondria and decarboxylated to phosphatidylisopropanolamine therein. We studied this issue with hamster kidney cell-line using a novel approach, i.e. electrospray mass-spectrometry and stable isotope-labeled precursors. Scanning for a neutral loss of 155, which is characteristic for phosphatidylisopropanolamine, indicated that this lipid is indeed present. The identity of phosphatidylisopropanolamine was supported by the following: (i) it co-chromatographed with phosphatidylethanolamine; (ii) its molecular species profile was similar to that of phosphatidylethanolamine; (iii) its head group was labeled from ¹³C-threonine; and (iv) its concentration increased in parallel with phosphatidylthreonine. Tests with solubilized decarboxylase and subcellular fractionation studies indicated that the low cellular content of phosphatidylisopropanolamine is due to inefficient decarboxylation, rather than poor translocation of phosphatidylthreonine to mitochondria. Importantly, the average hydrophobicity of phosphatidylisopropanolamine molecular species was significantly less than that of phosphatidylthreonine species, indicating that hydrophilic phosphatidylthreonine species translocate to mitochondria far more rapidly than hydrophobic ones. Parallel results were obtained for phosphatidylserine. These findings imply that efflux from the ER membrane could be the rate-limiting step in the phosphatidylthreonine and -serine translocation to mitochondria.     

Plant litter chemistry alters the content and composition of organic carbon associated with soil mineral and aggregate fractions in invaded ecosystems

Through the input of disproportionate quantities of chemically distinct litter, invasive plants may potentially influence the fate of organic matter associated with soil mineral and aggregate fractions in some of the ecosystems they invade. Although context dependent, these native ecosystems subjected to prolonged invasion by exotic plants may be instrumental in distinguishing the role of plant–microbe–mineral interactions from the broader edaphic and climatic influences on the formation of soil organic matter (SOM). We hypothesized that the soils subjected to prolonged invasion by an exotic plant that input recalcitrant litter (Japanese knotweed, Polygonum cuspidatum) would have a greater proportion of plant‐derived carbon (C) in the aggregate fractions, as compared with that in adjacent soil inhabited by native vegetation that input labile litter, whereas the soils under an invader that input labile litter (kudzu, Pueraria lobata) would have a greater proportion of microbial‐derived C in the silt‐clay fraction, as compared with that in adjacent soils that receive recalcitrant litter. At the knotweed site, the higher C content in soils under P. cuspidatum, compared with noninvaded soils inhabited by grasses and forbs, was limited to the macroaggregate fraction, which was abundant in plant biomarkers. The noninvaded soils at this site had a higher abundance of lignins in mineral and microaggregate fractions and suberin in the macroaggregate fraction, partly because of the greater root density of the native species, which might have had an overriding influence on the chemistry of the above‐ground litter input. At the kudzu site, soils under P. lobata had lower C content across all size fractions at a 0–5 cm soil depth despite receiving similar amounts of Pinus litter. Contrary to our prediction, the noninvaded soils receiving recalcitrant Pinus litter had a similar abundance of plant biomarkers across both mineral and aggregate fractions, potentially because of the higher surface area of soil minerals at this site. The plant biomarkers were lower in the aggregate fractions of the P. lobata‐invaded soils, compared with noninvaded pine stands, potentially suggesting a microbial co‐metabolism of pine‐derived compounds. These results highlight the complex interactions among litter chemistry, soil biota, and minerals in mediating soil C storage in unmanaged ecosystems; these interactions are particularly important under global changes that may alter plant species composition and hence the quantity and chemistry of litter inputs in terrestrial ecosystems.     

糖皮质激素抑制加压素释放的细胞膜机制

利用离休孵育脑薄片和放射免疫测定其释放的精氨酸加压素（ＡＶＰ）方法,探讨糖皮质激素（ＧＣ）在不能进入细胞内的情况下,对去肾上腺大鼠的下丘脑薄片释放ＡＶＰ的快速影响及其可能的细胞膜机制。结果如下：（１）下丘脑薄片能够稳定地释放ＡＶＰ（２ｈ）,其释放量为１５．４２±１．２８ｐｇ／ｍｉｎ;（２）牛血清白蛋白耦联皮质酮（Ｂ－ＢＳＡ）对ＡＶＰ的释放具有快速的（２０ｍｉｎ）抑制性效应,在１０￣（－７）─１０￣（－４）ｍｏｌ／Ｌ范围内呈剂量一效应关系;（３）ＧＣ细胞内受体拮抗剂ＲＵ４８６（１０￣（－４）─１０￣（－３）ｍｏｌ／Ｌ）能部分地阻断Ｂ─ＢＳＡ的快速抑制效应;（４）孵育液中Ｃａ￣（２＋）程度升高,Ｂ─ＢＳＡ的快速抑制效应明显增强;反之,孵育液中无Ｃａ￣（２＋）则Ｂ－ＢＳＡ的快速抑制效应有所减弱。表明ＧＣ在未进入细胞内的情况下也可快速地抑制大鼠下丘脑薄片释放ＡＶＰ,因此没有通过传统的基因组机制,而是由非基因组机制介导的,其作用部位在细胞膜水平上,可能是影响Ｃａ￣（２＋）的跨细胞膜内流通量或／和影响有Ｃａ￣（２＋）参与的ＡＶＰ释放过程的结果。     

益生菌的多重抗病毒作用及其机制

病毒性疾病对人类和动物健康造成了重大威胁。由于现有的免疫接种和抗病毒疗法的局限性,开发安全、广谱、廉价的新型抗病毒制剂极为迫切。益生菌是摄入后能对机体产生多种有益作用的活性微生物,其抗病毒作用及潜在机制是当前的研究热点。本文介绍了益生菌通过促进肠道细胞的紧密连接和产生有利物质来维护机体黏膜屏障;与病毒竞争结合靶点或直接捕获并抑杀病毒;刺激机体免疫系统,调节固有免疫反应和适应性免疫反应;分泌具有抗病毒作用的代谢产物来发挥抗病毒作用及其作用机制,以期为益生菌的抗病毒相关研究提供参考。     

光呼吸研究进展

光呼吸是指植物绿色组织依赖光能吸收O₂并释放CO₂的过程,它被认为是一个浪费能量的过程。正常生长的C₃植物光呼吸可损耗光合产物的25%~30%,在干旱、高温、高光等逆境胁迫下,该损耗可高达50%,因此,显著提高C₃植物的生产力可通过减少光呼吸通量来实现。尽管光呼吸对植物生产力的负面影响明显,但它对植物一些必要生理活动可能起着重要作用,其中包括参与光保护、H₂O₂信号发生、氮代谢、光氧化和抗逆反应等。该文对光呼吸的改造优化需要把握好平衡点与适配度。基于Rubisco改造、CO₂浓缩机制(CCM)和光呼吸支路创建的光呼吸改造研究进展进行了综述。通过了解调控光呼吸提高植物光能转化效率方面的最新进展, 可望为光呼吸代谢的分子调控及改良研究提供指导。     

LncRNA AL133467.1作为miR-661的ceRNA抑制乳腺癌细胞增殖和侵袭

长非编码RNAs((long non-coding RNAs,lncRNAs)在多种肿瘤中异常表达并参与肿瘤的发生发展.然而,众多lncRNAs在肿瘤的表达及功能尚未完全阐明.本文通过分析TCGT数据库113例正常乳腺组织和1109例乳腺癌组织发现,LneRNA AL133467.1在乳腺癌组织中低表达,并与乳腺癌患者...     

兴安落叶松叶光合与氮代谢对环境变化响应的转录组分析

为了揭示兴安落叶松针叶光合作用对环境变化响应的分子机制,采用高通量测序技术,对生长环境差异明显的4个样地[塔河(52°52′ N)、松岭(50°72′ N)、黑河(49°22′ N)和带岭(47°08′ N)]兴安落叶松针叶进行转录组测序,并比对不同样地树木针叶的差异表达基因(DEGs)。结果表明: 共获得高质量短读序282428811条,其中在塔河-松岭、塔河-黑河、塔河-带岭、松岭-黑河、松岭-带岭、黑河-带岭6个对比组中,分别筛选出16915、18812、28536、20635、29957和23617条差异表达基因。在KEGG代谢通路分析中,光合作用通路中编码光系统Ⅱ(PSⅡ)的Psb基因家族的9个基因(即PsbB、PsbK、PsbO、PsbP、PsbQ、PsbS、PsbW、Psb27和Psb28)及编码F型ATP酶的3个基因(即ATPF1A, atpA、ATPF1G, atpG和ATPF1D, atpH)均随样地间的环境差异增大而呈现明显上调;氮代谢通路中编码谷氨酰胺合成酶的基因(glnA, GLUL)、硝酸还原酶的基因(NR)、碳酸酐酶的基因(cynT,can)也呈现同样的上调。DEGs和上调基因的数量均随样地环境变化增大而增多,进而导致了兴安落叶松针叶光合能力在样地间的差异。     

人工微生物混菌系统机制解析中的组学应用及进展

人工微生物混菌系统的生物工程应用价值日益受到重视,使得对于混菌系统中成员菌间的相互作用机制研究也成为近年来的一个热点.其研究结果一方面可以为现有人工混菌系统的进一步优化提供理论依据,另一方面也为全新混菌系统的人工构建提供新的思路和策略,进而促进人工微生物混菌系统未来规模化应用.基因组学、转录组学、蛋白质组学和代谢组学等...     

藻菌共生处理污水的机制与应用研究进展

在污水处理领域,藻菌共生有同步脱氮、除磷效率高、排放温室气体量低、生物质可资源化回收等优势,近年来受到学者的重视.目前鲜有综述污水处理中藻类与细菌、真菌及混合藻菌间互作机制的文章.本文从藻类-细菌、藻类-真菌、混合藻-混合菌3个方面介绍藻菌共生处理污水的研究进展,重点阐述藻菌间营养物质交换、信号传导及生物絮凝3种不同互...