Influence of membrane-cortex linkers on the extrusion of membrane tubes

The cell membrane is an inhomogeneous system composed of phospholipids, sterols, carbohydrates, and proteins that can be directly attached to underlying cytoskeleton. The protein linkers between the membrane and the cytoskeleton are believed to have a profound effect on the mechanical properties of the cell membrane and its ability to reshape. Here, we investigate the role of membrane-cortex linkers on the extrusion of membrane tubes using computer simulations and experiments. In simulations, we find that the force for tube extrusion has a nonlinear dependence on the density of membrane-cortex attachments: at a range of low and intermediate linker densities, the force is not significantly influenced by the presence of the membrane-cortex attachments and resembles that of the bare membrane. For large concentrations of linkers, however, the force substantially increases compared with the bare membrane. In both cases, the linkers provided membrane tubes with increased stability against coalescence. We then pulled tubes from HEK cells using optical tweezers for varying expression levels of the membrane-cortex attachment protein Ezrin. In line with simulations, we observed that overexpression of Ezrin led to an increased extrusion force, while Ezrin depletion had a negligible effect on the force. Our results shed light on the importance of local protein rearrangements for membrane reshaping at nanoscopic scales.     

Genetic Analysis of Human Adenovirus Type 7 Strains Circulating in Different Parts of China

To investigate the molecular epidemiology and genetic variation of human adenovirus type 7(HAdV-7) in children with acute respiratory infections(ARI) in China. HAdV-7-positive respiratory samples collected from children with ARI in Beijing, Shijiazhuang, Wenzhou and Guangzhou from 2014–2018 were selected for gene amplification and sequence analysis. Fifty-seven HAdV-7 clinical strains with hexon, penton base and fiber gene sequences were obtained. Meanwhile17 strains were selected randomly from different cities for whole genome sequencing. Phylogenetic and variation analyses were performed based on the obtained sequences, HAdV-7 prototype strain Gomen(AY594255), vaccine strains(AY495969 and AY594256) and representative sequences of strains. The phylogenetic trees constructed based on whole genome sequences, major capsid protein genes(hexon, penton base and fiber) and the early genes(E1, E2, E3 and E4) were not completely consistent. The HAdV-7 strains obtained in this study always clustered with most of the circulating strains worldwide from the 1980 s to the present. Compared with the HAdV-7 prototype strain Gomen(AY594255), some amino acid mutations in loop1 and loop2 of hexon and the RGD loop region of the penton base gene were observed. Recombination analysis showed that partial regions of 55 k Da protein and 100 kDa hexon-assembly associated protein genes among all HAdV-7 strains in this study were from HAdV-16 and HAdV-3, respectively. Our study demonstrated the molecular evolution characteristics of HAdV-7 strains circulating in China and provided basic reference data for the prevention, control and vaccine development of HAdV-7.     

北盘江大峡谷流域浮游生物资源调查及多样性分析

为探究北盘江大峡谷流域内浮游生物群落组成及多样性情况,于2017年10月对该流域进行浮游生物调查及多样性分析.结果表明该流域内浮游植物共有7门40属61种、其中绿藻门、硅藻门和蓝藻门种类分别为21种、19种和12种,分别占到34.43％、31.15％和19.67％,浮游植物平均密度为4 298.33(375～9 500)ind./L,Shannon-Wiener藻类生物多样性指数均处于1和2之间;浮游动物3门12属21种,其中轮虫类、枝角类和桡足类种类分别为11种、5种和5种,各占到52.38％、23.81％和23.81％,浮游动物平均密度为436.11(55～1 437.5)ind./L,Shannon-Wiener生物多样性指数均处于1和2之间.本研究结果该地区水生生物资源积累了本底资料.     

CX3CL1 promotes tumour cell by inducing tyrosine phosphorylation of cortactin in lung cancer

It has been reported that chemokine CX₃CL1 can regulate various tumours by binding to its unique receptor CX₃CR1. However, the effect of CX₃CL1-CX₃CR1 on the lung adenocarcinoma and lung squamous cell carcinoma is still unclear. Here, we showed that CX₃CL1 can further invasion and migration of lung adenocarcinoma A549 and lung squamous cell carcinoma H520. In addition, Western blot and immunofluorescence test indicated CX₃CL1 up-regulated the phosphorylation level of cortactin, which is a marker of cell pseudopodium. Meanwhile, the phosphorylation levels of c-Src and c-Abl, which are closely related to the regulation of cortactin phosphorylation, are elevated. Nevertheless, the src/abl inhibitor bosutinib and mutations of cortactin phosphorylation site could inhibit the promotion effect of CX₃CL1 on invasion and migration of A549 and H520. Moreover, these results of MTT, Hoechst staining and Western blot suggested that CX₃CL1 had no effect on the proliferation and apoptosis of A549 and H520 in vitro. The effects of CX₃CL1 were also verified by the subcutaneous tumour formation in nude mice, which showed that it could promote proliferation and invasion of A549 in vivo. In summary, our results indicated that CX₃CL1 furthered invasion and migration in lung cancer cells partly via activating cortactin, and CX₃CL1 may be a potential molecule in regulating the migration and invasion of lung cancer.     

Targeting P2 receptors in purinergic signaling: a new strategy of active ingredients in traditional Chinese herbals for diseases treatment

Adenosine triphosphate (ATP) and its metabolites adenosine diphosphate, adenosine monophosphate, and adenosine in purinergic signaling pathway play important roles in many diseases. Activation of P2 receptors (P2R) channels and subsequent membrane depolarization can induce accumulation of extracellular ATP, and furtherly cause kinds of diseases, such as pain- and immune-related diseases, cardiac dysfunction, and tumorigenesis. Active ingredients of traditional Chinese herbals which exhibit superior pharmacological activities on diversified P2R channels have been considered as an alternative strategy of disease treatment. Experimental evidence of potential ingredients in Chinese herbs targeting P2R and their pharmacological activities were outlined in the study.

     

Long noncoding RNA ATB promotes ovarian cancer tumorigenesis by mediating histone H3 lysine 27 trimethylation through binding to EZH2

Ovarian cancer (OC) remains one of the most lethal gynecological malignancies. The unfavourable prognosis is mainly due to the lack of early-stage diagnosis, drug resistance and recurrence. Therefore, it needs to investigate the mechanism of OC tumorigenesis and identify effective biomarkers for the clinical diagnosis. It is reported that long noncoding RNAs (lncRNAs) play important roles during the tumorigenesis of OC. Therefore, the present study aimed to study the role and clinical significance of LncRNAs ATB (lnc-ATB) in the development and progression of OC. In our research, lnc-ATB expression in OC tissues was elevated compared with adjacent normal tissues and high expression of lnc-ATB was associated with poor outcomes of OC patients. The silencing of lnc-ATB blocked cell proliferation, invasion and migration in SKOV3 and A2780 cells. RNA immunoprecipitation and RNA pull-down results showed that lnc-ATB positively regulated the expression of EZH2 via directly interacting with EZH2. Besides, the overexpression of EZH2 partly rescued lnc-ATB silencing-inducing inhibition of cell proliferation, invasion and migration. Chromatin immunoprecipitation assay results demonstrated that the silencing of lnc-ATB reduced the occupancy of caudal-related homeobox protein 1, Forkhead box C1, Large tumour suppressor kinase 2, cadherin-1 and disabled homolog 2 interacting protein promoters on EZH2 and H3K27me3. These data revealed the oncogenic of lnc-ATB and provided a novel biomarker for OC diagnosis. Furthermore, these findings indicated the mechanism of lnc-ATB functioning in the progression of OC, which provided a new target for OC therapy.     

传粉昆虫下降背景下的授粉生态弹性: 内涵、机制和展望

全球传粉昆虫多样性正在下降, 如何保障农林生态系统传粉功能是当前研究的热点。理论上说, 传粉功能不仅与生态系统的传粉昆虫多样性相关, 还与生态系统的调节能力有关。近年来, 学者们逐渐认识到授粉生态弹性对传粉功能的影响。本文在回顾已有研究的基础之上, 总结传粉昆虫授粉生态弹性的内涵, 厘清授粉生态弹性与工程弹性、稳定性和抗性的异同。目前, 学者对授粉生态弹性形成机制开展广泛探讨, 提出功能冗余假说、密度补偿假说、响应多样性假说、连接周转假说和跨尺度弹性假说, 但这5个假说间的关系仍不清楚, 存在一词多义、词意混淆等现象。我们依次阐述功能冗余假说、密度补偿假说、响应多样性假说、连接周转假说和跨尺度弹性假说, 介绍不同假说中授粉生态弹性形成过程、研究热点和发展动态。通过解析授粉生态弹性的形成机制可知, 5个假说在内涵上存在紧密联系, 它们从不同空间尺度和研究对象下解释传粉昆虫授粉生态弹性的形成机制。未来授粉生态弹性研究将整合传粉昆虫群落动态和传粉功能动态的量化方法, 通过实验验证5个假说的合理性, 并揭示不同假说间的联系, 由此阐明授粉生态弹性的发生条件、形成阈值和动态规律。随着研究的深入, 授粉生态弹性理论有望用于指导农林生态系统传粉功能的经营管理。     

支气管镜肺泡灌洗联合抗生素对小儿重症肺炎的疗效及对痰细菌清除率等指标的影响

目的探讨支气管镜肺泡灌洗联合抗生素对小儿重症肺炎的疗效及对痰细菌清除率和其他指标的影响。方法选取我科收治的重症肺炎患儿126例,分为研究组及对照组,各63例。其中研究组在常规治疗基础上联合支气管镜肺泡灌洗及局部应用抗生素治疗,对照组采用常规治疗,比较2组患者的临床治疗效果。结果治疗后,研究组的临床有效率为90.5%,高于对照组的76.2%(χ~2=4.629,P=0.031);治疗后研究组患者的痰液中病菌清除率为77.7%,显著高于对照组的57.2%(χ~2=6.110,P=0.013);治疗后研究组患者的相关炎性指标(高敏C反应蛋白、肿瘤坏死因子α及白介素-6)均较对照组显著降低(t=3.522、4.912、4.183,P=0.033、0.032、0.033);治疗后研究组患者的相关血气指标(动脉血氧分压及氧合指数)均较对照组显著升高,而二氧化碳分压较对照组显著降低(t=3.612、3.312、6.162,P=0.039、0.040、0.028)。结论 BAL联合抗生素对小儿重症肺炎的疗效更为显著,值得临床推广应用。