miR‐200c suppresses stemness and increases cellular sensitivity to trastuzumab in HER2+ breast cancer

Resistance to trastuzumab remains a major obstacle in HER2‐overexpressing breast cancer treatment. miR‐200c is important for many functions in cancer stem cells (CSCs), including tumour recurrence, metastasis and resistance. We hypothesized that miR‐200c contributes to trastuzumab resistance and stemness maintenance in HER2‐overexpressing breast cancer. In this study, we used HER2‐positive SKBR3, HER2‐negative MCF‐7, and their CD44⁺CD24^? phenotype mammospheres SKBR3‐S and MCF‐7‐S to verify. Our results demonstrated that miR‐200c was weakly expressed in breast cancer cell lines and cell line stem cells. Overexpression of miR‐200c resulted in a significant reduction in the number of tumour spheres formed and the population of CD44⁺CD24^? phenotype mammospheres in SKBR3‐S. Combining miR‐200c with trastuzumab can significantly reduce proliferation and increase apoptosis of SKBR3 and SKBR3‐S. Overexpression of miR‐200c also eliminated its downstream target genes. These genes were highly expressed and positively related in breast cancer patients. Overexpression of miR‐200c also improved the malignant progression of SKBR3‐S and SKBR3 in vivo. miR‐200c plays an important role in the maintenance of the CSC‐like phenotype and increases drug sensitivity to trastuzumab in HER2+ cells and stem cells.     

粘性丝孢酵母的诱变及以玉米秸秆水解液为原料产油条件优化

对粘性丝胞酵母进行紫外诱变,获得一株产油率较高的菌株,较原菌株提高了1.53倍。将该菌株接种于用1%硫酸和酶水解处理并浓缩至还原糖浓度为5%的玉米秸秆水解液中培养,生长较好。通过四因素三水平正交实验,确定培养条件为初始pH值7.0、接种量1%、发酵温度30℃、发酵时间5 d时产油率最高。对最佳产油条件进行验证,测得油脂含量为21.3%。从而为利用农业废弃物大规模生产微生物油脂提供了试验数据。气相色谱-质谱联用分析仪显示油脂脂肪酸组成为棕榈酸28.36%,油酸55.86%,10-十八烯酸9.23%,硬脂酸6.70%,可以作为原料生产生物柴油。     

Enantiomeric Polyketides from the Starfish‐Derived Symbiotic Fungus Penicillium sp. GGF16‐1‐2

One new racemic mixture, penicilliode A ( 1 ) and four pairs of enantiomeric polyketides, penicilliode B and C ( 2 and 3 ) and coniochaetone B and C ( 4 and 5 ), were obtained from the starfish‐derived symbiotic fungus Penicillium sp. GGF16‐1‐2. Interestingly, the strain GGF16‐1‐2 can produce enantiomers. The absolute configuration of 1 was determined by X‐ray diffraction (XRD) analysis, and the absolute configurations of 2 – 4 were determined by the optical rotation (OR) values and electronic circular dichroism (ECD) calculations. Compounds 1 – 5 were firstly isolated from the marine‐derived fungus Penicillium as racemates, and 2 – 5 were separated by HPLC with a chiral stationary phase. All the compounds were evaluated for their antibacterial, cytotoxic and inhibitory activities against PDE4D2.     

Molecular dynamics simulation on the allosteric analysis of the c‐di‐GMP class I riboswitch induced by ligand binding

Riboswitches are RNA molecules that regulate gene expression using conformation change, affected by binding of small molecule ligands. Although a number of ligand‐bound aptamer complex structures have been solved, it is important to know ligand‐free conformations of the aptamers in order to understand the mechanism of specific binding by ligands. In this paper, we use dynamics simulations on a series of models to characterize the ligand‐free and ligand‐bound aptamer domain of the c‐di‐GMP class I (GEMM‐I) riboswitch. The results revealed that the ligand‐free aptamer has a stable state with a folded P2 and P3 helix, an unfolded P1 helix and open binding pocket. The first Mg ions binding to the aptamer is structurally favorable for the successive c‐di‐GMP binding. The P1 helix forms when c‐di‐GMP is successive bound. Three key junctions J1/2, J2/3 and J1/3 in the GEMM‐I riboswitch contributing to the formation of P1 helix have been found. The binding of the c‐di‐GMP ligand to the GEMM‐I riboswitch induces the riboswitch's regulation through the direct allosteric communication network in GEMM‐I riboswitch from the c‐di‐GMP binding sites in the J1/2 and J1/3 junctions to the P1 helix, the indirect ones from those in the J2/3 and P2 communicating to P1 helix via the J1/2 and J1/3 media.     

荒漠杜加依林冠层水热变化及CO2交换特征

选取新疆艾比湖湿地国家级自然保护区荒漠杜加依林为研究对象,利用通量塔连续观测数据分析新疆艾比湖流域内杜加依林冠层界面水热垂直变化和CO_2交换特征,进一步比较了冠层界面湍流碳通量、植物冠层储存碳通量及净碳交换量,探讨了不同时间和垂直空间序列下杜加依林冠层界面温湿廓线与CO_2交换过程的相互关系。结果表明,新疆艾比湖流域内杜加依林冠层上方大气稳定度生长季的6—9月为中性(z/L=0.009),非生长季为不稳定(z/L=-0.449),全年总体呈不稳定水平(z/L=-0.194);冠层界面上气温垂直变幅小于5℃,随高度呈递增趋势,湿度垂直变幅超过40%;地-气碳通量呈秋冬小春夏大规律,年碳收支高于干旱区平均水平,为-0.026 mg CO_2m~(-2)s~(-1),表现为碳汇;垂直空间尺度上垂直温湿度差与生态系统净碳交换量(NEE,Net Ecosystem Exchange)拟合较好,温度拟合结果为R~2=0.7350(P﹤0.01),湿度拟合结果为R~2=0.3627(P﹤0.01),水热变点分别为5%和1℃,而季节尺度上温度拟合结果较好,温度拟合结果为R~2=0. 5221(P﹤0. 01),湿度拟合结果为R~2=0.1716(P﹤0.01),变点为55%和18℃。生长季较小的冠层垂直温差有利于杜加依林对大气CO_2的吸收,而冠层高湿环境则会抑制杜加依林对CO_2的吸收。     

细胞穿膜肽研究应用的新进展

细胞穿膜肽(Cell-penetrating peptides,CPPs)是一类能够穿过细胞膜或组织屏障的短肽。CPPs可通过内吞和直接穿透等机制运载蛋白质、RNA、DNA等生物大分子进入细胞内发挥其效应功能。相比于其他非天然的化学分子,CPPs具有生物相容性佳、对细胞造成的毒性小、完成入胞转运后可降解、并能与生物活性蛋白直接融合重组表达等优点,因此成为以胞内分子为靶标的药物递送技术发展的重要工具,并在生物医学研究领域具有良好的应用前景。文中针对CPPs的分类特点、入胞转运机制及其治疗应用的新近研究进展进行综述和讨论。     

Unplugging the callose plug from sieve pores

The presence of callose in sieve plates has been known for a long time, but how this polysaccharide plug is synthesized has remained unsolved. Two independent laboratories have recently reported the identification of callose synthase 7 (CalS7), also known as glucan synthase-like 7 (GSL7), as the enzyme responsible for callose deposition in sieve plates. Mutant plants defective in this enzyme failed to synthesize callose in developing sieve plates during phloem formation and were unable to accumulate callose in sieve pores in response to stress treatments. The mutant plants developed less open pores per sieve plate and the pores were smaller in diameter. As a result, phloem conductivity was reduced significantly and the mutant plants were shorter and set fewer seeds.Key words: Arabidopsis thaliana, callose, callose synthase, glucan synthase-like, phloem, plasmodesmata, sieve plate     

Development of micropost force sensor array with culture experiments for determination of cell traction forces

Cell traction forces (CTFs) are critical for cell motility and cell shape maintenance. As such, they play a fundamental role in many biological processes such as angiogenesis, embryogenesis, inflammation, and wound healing. To determine CTFs at the sub-cellular level with high sensitivity, we have developed high density micropost force sensor array (MFSA), which consists of an array of vertically standing poly(dimethylsiloxane) (PDMS) microposts, 2 microm in diameter and 6 microm in height, with a center-to-center distance of 4 microm. In combination with new image analysis algorithms, the MFSA can achieve a spatial resolution of 40 nm and a force sensitivity of 0.5 nN. Culture experiments with various types of cells showed that this MFSA technology can effectively determine CTFs of cells with different sizes and traction force magnitudes.