Dynamic expression of miR-126 and its effects on proliferation and contraction of hepatic stellate cells

In our previous study, miR-126 was identified as one of the leading miRNAs that is downregulated during activation of hepatic stellate cells (HSCs). However, the roles and related mechanisms of miR-126 in HSCs are not understood. In this study, we compared expression of miR-126 during HSC activation both in vitro and in vivo. We also applied RNA interference to analyze the role and mechanism of miR-126^∗ in the activation of HSCs. Restoring HSCs with Lv-miR-126^∗ resulted in decreased proliferation, accumulation of extracellular matrix components, and cell contraction, while also negatively regulating the vascular endothelial growth factor (VEGF) signal transduction pathways by partially targeted VEGF-A. Thus, we postulate that miR-126 may be a biological marker for the activation of HSCs, and useful for reducing intrahepatic vascular resistance and improving the sinusoidal microcirculation in chronic liver diseases.     

Pip介导铜绿假单胞菌吩嗪基因簇phz2的表达

[目的]为了确定铜绿假单胞菌调控因子Pip对两个不同吩嗪合成基因簇(phz1和phz2)的具体调控方式与可能的调控机制.[方法]根据基因比对结果,采用同源重组技术构建Pip调控因子缺失突变株PA-PG以及克隆ip基因作互补分析;再以已构建的吩嗪基因簇缺失突变株PA-Z1G和PA-Z2K为受体菌,构建突变株PA-PD-Z1G和PA-PG-Z2K,测定并比较野生株及相关突变株的吩嗪-1-羧酸和绿脓菌素的合成量,推定Pip对两个不同吩嗪合成基因簇的调控方式.[结果]在GA培养基中,突变株PA-PG的吩嗪-1-羧酸和绿脓菌素都比野生型明显减少;互补分析显示,突变株PA-PG的吩嗪-1-羧酸和绿脓菌素都显著提高并恢复到野生株PAO1水平;突变株PA-Z1G的吩嗪-1-羧酸和绿脓菌素合成量因Pip缺失而显著减少;而突变株PA-Z2K的吩嗪-1-羧酸和绿脓菌素合成量在Pip缺失后仍保持不变.[结论]初步推定,转录调控因子Pip对铜绿假单胞菌吩嗪合成代谢的确具有促进作用;Pip通过正向调控吩嗪基因簇phz2的合成功能实现对吩嗪合成代谢的调控.     

不同成熟度煤样产甲烷潜力

摘要:【目的】评估不同类型煤炭生物降解转化为甲烷的潜力,研究原位煤层的微生物群落结构特征。【方法】分别在原位模拟、补加烃降解产甲烷菌系和补加碳源下厌氧培养煤样,利用气相色谱监测甲烷产生趋势,及高通量测序技术研究原位煤层的细菌和古菌群落。【结果】10个样品中有3个高成熟度煤样可以被厌氧降解转化为甲烷。通过生物强化和添加外源底物可以促进HF煤样的产甲烷潜力。其中SL 煤样中的古菌类群主要是氢营养型产甲烷菌Methanoculleus和乙酸营养型产甲烷菌Methanosaeta为主,细菌类群主要 属于Firmicutes(54.4%)、Proteobacteria(30.9%)、未培养微生物(10.8%)、Caldiserica(1.5%)及Thermotogae(1.3%)。【结论】不同成熟度煤样降解产气潜力不同,在部分原位煤层中可能存在参与烃降解与甲烷产生的功能菌。     

云南阳宗海酵母菌种群结构及产胞外酶测试北大核心CSCD

【目的】研究阳宗海酵母菌种群结构,分析生物因子及非生物因子对酵母菌种群分布的影响;测试阳宗海酵母菌产胞外酶活性。【方法】水样用醋酸纤维素滤膜过滤,原位培养分离酵母菌;梯度稀释法分离土样和底泥样品;对分离得到的菌株进行DNA提取和测序,分析26S rDNA的D1/D2区域,并结合形态及生理生化指标进行鉴定;用产酶筛选培养基对分离得到的酵母菌进行产胞外酶活性测试。【结果】共分离得到201株酵母菌,鉴定分属于15个属48个种,其中包括10个潜在的新种;普鲁兰类酵母(Aureobasidium pullulans),库德里阿兹威氏毕赤酵母(Pichia kudriavzevii),胶红酵母(Rhodotorula mucilaginosa),Cryptococcus podzolicus是优势种;15.9%的酵母菌具有产胞外酶活性,主要是脂肪酶和淀粉酶。【结论】阳宗海酵母菌有较为丰富的多样性,人为活动对阳宗海酵母菌分布影响较大,其次浊度、电导率也是影响酵母菌种群分布的重要因素;阳宗海产胞外酶酵母菌可能参与湖泊生态系统的自然循环。     

Evolutionary transition from C3 to C4 photosynthesis and the route to C4 rice

Compared with C₃ plants, C₄ plants possess a mechanism to concentrate CO₂ around the ribulose-1,5-bisphosphate carboxylase/oxygenase in chloroplasts of bundle sheath cells so that the carboxylation reaction work at a much more efficient rate, thereby substantially eliminate the oxygenation reaction and the resulting photorespiration. It is observed that C₄ photosynthesis is more efficient than C₃ photosynthesis under conditions of low atmospheric CO₂, heat, drought and salinity, suggesting that these factors are the important drivers to promote C₄ evolution. Although C₄ evolution took over 66 times independently, it is hypothesized that it shared the following evolutionary trajectory: 1) gene duplication followed by neofunctionalization; 2) anatomical and ultrastructral changes of leaf architecture to improve the hydraulic systems; 3) establishment of two-celled photorespiratory pump; 4) addition of transport system; 5) co-option of the duplicated genes into C₄ pathway and adaptive changes of C₄ enzymes. Based on our current understanding on C₄ evolution, several strategies for engineering C₄ rice have been proposed to increase both photosynthetic efficiency and yield significantly in order to avoid international food crisis in the future, especially in the developing countries. Here we summarize the latest progresses on the studies of C₄ evolution and discuss the strategies to introduce two-celled C₄ pathway into rice.     

A rice lectin receptor‐like kinase that is involved in innate immune responses also contributes to seed germination

Seed germination and innate immunity both have significant effects on plant life spans because they control the plant's entry into the ecosystem and provide defenses against various external stresses, respectively. Much ecological evidence has shown that seeds with high vigor are generally more tolerant of various environmental stimuli in the field than those with low vigor. However, there is little genetic evidence linking germination and immunity in plants. Here, we show that the rice lectin receptor‐like kinase OslecRK contributes to both seed germination and plant innate immunity. We demonstrate that knocking down the OslecRK gene depresses the expression of α–amylase genes, reducing seed viability and thereby decreasing the rate of seed germination. Moreover, it also inhibits the expression of defense genes, and so reduces the resistance of rice plants to fungal and bacterial pathogens as well as herbivorous insects. Yeast two‐hybrid and co‐immunoprecipitation experiments revealed that OslecRK interacts with an actin‐depolymerizing factor (ADF) in vivo via its kinase domain. Moreover, the rice adf mutant exhibited a reduced seed germination rate due to the suppression of α–amylase gene expression. This mutant also exhibited depressed immune responses and reduced resistance to biotic stresses. Our results thus provide direct genetic evidence for a common physiological pathway connecting germination and immunity in plants. They also partially explain the common observation that high‐vigor seeds often perform well in the field. The dual effects of OslecRK may be indicative of progressive adaptive evolution in rice.     

Phenanthroimidazole-based thiobenzamide as an effective sensor for highly selective detection of mercury(II)

Based on highly selective and irreversible Hg²⁺-promoted desulfurization reaction, a new and simple phenanthroimidazole-type sensor was prepared and exhibited high selectivity towards Hg²⁺ ion over other metal ions, accompanied by transformation of a weakly fluorescent thioamide moiety (colorless) to a highly fluorescent amide one (blue), with a 136-fold increase in fluorescent intensity in aqueous solution with a pH span 2.57–9.12.     

Pyrido[2,3-d]pyrimidines: Discovery and preliminary SAR of a novel series of DYRK1B and DYRK1A inhibitors

DYRK1B is a kinase over-expressed in certain cancer cells (including colon, ovarian, pancreatic, etc.). Recent publications have demonstrated inhibition of DYRK1B could be an attractive target for cancer therapy. From a data-mining effort, the team has discovered analogues of pyrido[2,3-d]pyrimidines as potent enantio-selective inhibitors of DYRK1B. Cells treated with a tool compound from this series showed the same cellular effects as down regulation of DYRK1B with siRNA. Such effects are consistent with the proposed mechanism of action. Progress of the SAR study is presented.     

Design,synthesis, and biological evaluation of novel histone deacetylase 1 inhibitors through click chemistry

We report the design, synthesis, and biological evaluation of a new series of HDAC1 inhibitors using click chemistry. Compound 17 bearing a phenyl ring at meta-position was identified to show much better selectivity for HDAC1 over HDAC7 than SAHA. The compond 17 also showed better in vitro anticancer activities against several cancer cell lines than that of SAHA. This work could serve as a foundation for further exploration of selective HDAC inhibitors using the compound 17 molecular scaffold.     

Conformational stability of CopC and roles of residues Tyr79 and Trp83

CopC is a periplasmic copper Chaperone protein that has a β‐barrel fold and two metal‐binding sites distinct for Cu(II) and Cu(I). In the article, four mutants (Y79F, Y79W, Y79WW83L, Y79WW83F) were obtained by site‐directed mutagenesis. The far‐UV CD spectra of the proteins were similar, suggesting that mutations did not bring any significant changes in secondary structures. Meanwhile the effects of mutations on the protein's function were manifested by Cu(II) binding. Fluorescence lifetime measurement and quenching of tryptophan fluorescence by acrylamide and KI showed that the microenvironment around Trp83 was more hydrophobic than that around Tyr79 in apoCopC. Unfolding experiments induced by guanidinium chloride (GdnHCl), urea provided the conformational stability of each protein. The Δ<ΔG⁰_element> obtained using the model of structural elements was used to show the role of Tyr79 and Trp83. On the one hand, the <ΔG⁰_element> induced by urea for Y79F, Y79W have a loss of 6.51, 2.03 kJ/mol, respectively, compared with apoCopC, proving that replacement of Tyr79 by Phe or Trp all decreased the protein stability, meaning that the hydrogen bonds interactions between Tyr79 and Thr75 played an important role in stabilizing apoCopC. On the other hand, the <ΔG⁰_element> induced by urea for Y79WW83L have a loss of 11.44 kJ/mol, but for Y79WW83F did a raise of 1.82 kJ/mol compared with Y79W. The replacement of Trp83 by Phe and Leu yields opposite effects on protein stability, which suggested that the aromatic ring of Trp83 was important in maintaining the hydrophobic core of apoCopC.