Post-Translational Modifications of Retroviral HIV-1 Gag Precursors: An Overview of Their Biological Role

Protein post-translational modifications (PTMs) play key roles in eukaryotes since they finely regulate numerous mechanisms used to diversify the protein functions and to modulate their signaling networks. Besides, these chemical modifications also take part in the viral hijacking of the host, and also contribute to the cellular response to viral infections. All domains of the human immunodeficiency virus type 1 (HIV-1) Gag precursor of 55-kDa (Pr55^Gag), which is the central actor for viral RNA specific recruitment and genome packaging, are post-translationally modified. In this review, we summarize the current knowledge about HIV-1 Pr55^Gag PTMs such as myristoylation, phosphorylation, ubiquitination, sumoylation, methylation, and ISGylation in order to figure out how these modifications affect the precursor functions and viral replication. Indeed, in HIV-1, PTMs regulate the precursor trafficking between cell compartments and its anchoring at the plasma membrane, where viral assembly occurs. Interestingly, PTMs also allow Pr55^Gag to hijack the cell machinery to achieve viral budding as they drive recognition between viral proteins or cellular components such as the ESCRT machinery. Finally, we will describe and compare PTMs of several other retroviral Gag proteins to give a global overview of their role in the retroviral life cycle.     

Synthesis and Pharmacological In Vitro Investigations of Novel Shikonin Derivatives with a Special Focus on Cyclopropane Bearing Derivatives

Melanoma is the deadliest form of skin cancer and accounts for about three quarters of all skin cancer deaths. Especially at an advanced stage, its treatment is challenging, and survival rates are very low. In previous studies, we showed that the constituents of the roots of Onosma paniculata as well as a synthetic derivative of the most active constituent showed promising results in metastatic melanoma cell lines. In the current study, we address the question whether we can generate further derivatives with optimized activity by synthesis. Therefore, we prepared 31, mainly novel shikonin derivatives and screened them in different melanoma cell lines (WM9, WM164, and MUG-Mel2 cells) using the XTT viability assay. We identified (R)-1-(1,4-dihydro-5,8-dihydroxy-1,4-dioxonaphthalen-2-yl)-4-methylpent-3-enyl 2-cyclopropyl-2-oxoacetate as a novel derivative with even higher activity. Furthermore, pharmacological investigations including the ApoToxGlo^TM Triplex assay, LDH assay, and cell cycle measurements revealed that this compound induced apoptosis and reduced cells in the G1 phase accompanied by an increase of cells in the G2/M phase. Moreover, it showed hardly any effects on the cell membrane integrity. However, it also exhibited cytotoxicity against non-tumorigenic cells. Nevertheless, in summary, we could show that shikonin derivatives might be promising drug leads in the treatment of melanoma.     

焊接构造对T型接头超低周疲劳性能的影响

为了研究焊接细节对钢结构超低周疲劳性能的影响,以T型接头为对象,在通用有限元程序Abaqus平台上,开发基于Arlequin算法的结构多尺度计算程序. 利用多尺度算法,开展焊接接头的局部弹塑性有限元分析. 比较焊趾半径、厚钢板未熔透长度及焊趾表面凹凸对局部塑性应变履历的影响,利用Coffin-Manson模型对T型接头的超低周疲劳特性进行定性讨论. 数值计算结果表明,焊趾位置是焊接接头的超低周疲劳易损位置,厚钢板的未熔透长度对焊接部位局部塑性应变的影响不大;焊趾半径对焊趾局部塑性应变有较大的影响,增大焊趾半径可以有效提升钢结构在循环荷载下的超低周疲劳性能;焊趾表面的平整性是影响焊趾局部塑性应变履历的重要因素,尖锐的凹坑会明显降低焊接接头的超低周疲劳性能,磨平的焊趾表面可以减少局部塑性应变,提高接头的超低周疲劳强度.     

教育盛衰与王朝周期律

教育发展周期比王朝盛衰周期长。在同一教育发展周期内，王朝的衰落带来教育发展的小幅波动，新王朝创立之后能在较短的时间内修复原有的教育结构。而当教育结构自身开始坍塌的时候，王朝的衰落则明显加快这一坍塌的过程。教育结构的重建一般需要几个世纪，这一时期内王朝频繁更替，教育与王朝政治处于两衰的恶性循环中。教育与王朝政治的依存关系形成于春秋战国，巩固于西汉。僵硬的教育结构与人的创造力构成持续的冲突，最终导致教育结构的坍塌。     

不可逆量子斯特林热泵循环性能分析与优化

建立了以一维无限深势阱中极端相对论粒子为工质的不可逆量子斯特林热泵循环模型。考虑高低温热源之间的热漏,导出了循环的性能系数与无量纲泵热率的表达式。分析了循环性能与各性能参数之间的关系。研究发现,热泵的性能系数与无量纲泵热率都随粒子在状态1进处于激收态上的占有几度单调递减,性能系数与无量纲泵热率都是势阱宽度比的凸单调函数。无量纲泵热率关于性能系数的关系曲线为回原点的扭叶型,并确定了该不可逆量子斯特林热泵的最优运行区间。     

Proinflammatory Interleukin-33 Induces Dichotomic Effects on Cell Proliferation in Normal Gastric Epithelium and Gastric Cancer

Interleukin (IL)-33 is a member of the interleukin (IL)-1 family of cytokines linked to the development of inflammatory conditions and cancer in the gastrointestinal tract. This study is designed to investigate whether IL-33 has a direct effect on human gastric epithelial cells (GES-1), the human gastric adenocarcinoma cell line (AGS), and the gastric carcinoma cell line (NCI-N87) by assessing its role in the regulation of cell proliferation, migration, cell cycle, and apoptosis. Cell cycle regulation was also determined in ex vivo gastric cancer samples obtained during endoscopy and surgical procedures. Cell lines and tissue samples underwent stimulation with rhIL-33. Proliferation was assessed by XTT and CFSE assays, migration by wound healing assay, and apoptosis by caspase 3/7 activity assay and annexin V assay. Cell cycle was analyzed by means of propidium iodine assay, and gene expression regulation was assessed by RT-PCR profiling. We found that IL-33 has an antiproliferative and proapoptotic effect on cancer cell lines, and it can stimulate proliferation and reduce apoptosis in normal epithelial cell lines. These effects were also confirmed by the analysis of cell cycle gene expression, which showed a reduced expression of pro-proliferative genes in cancer cells, particularly in genes involved in G0/G1 and G2/M checkpoints. These results were confirmed by gene expression analysis on bioptic and surgical specimens. The aforementioned results indicate that IL-33 may be involved in cell proliferation in an environment- and cell-type-dependent manner.     

Simulated Microgravity Inhibits the Proliferation of Chang Liver Cells by Attenuation of the Major Cell Cycle Regulators and Cytoskeletal Proteins

Simulated microgravity (SMG) induced the changes in cell proliferation and cytoskeleton organization, which plays an important factor in various cellular processes. The inhibition in cell cycle progression has been considered to be one of the main causes of proliferation inhibition in cells under SMG, but their mechanisms are still not fully understood. This study aimed to evaluate the effects of SMG on the proliferative ability and cytoskeleton changes of Chang Liver Cells (CCL-13). CCL-13 cells were induced SMG by 3D clinostat for 72 h, while the control group were treated in normal gravity at the same time. The results showed that SMG reduced CCL-13 cell proliferation by an increase in the number of CCL-13 cells in G0/G1 phase. This cell cycle phase arrest of CCL-13 cells was due to a downregulation of cell cycle-related proteins, such as cyclin A1 and A2, cyclin D1, and cyclin-dependent kinase 6 (Cdk6). SMG-exposed CCL-13 cells also exhibited a downregulation of α-tubulin 3 and β-actin which induced the cytoskeleton reorganization. These results suggested that the inhibited proliferation of SMG-exposed CCL-13 cells could be associate with the attenuation of major cell cycle regulators and main cytoskeletal proteins.     

Robust Superhydrophobic Fabric for Durability,Self-Cleaning,and Oil/Water Separation via Thiol–Acrylate Polymerization

In recent years, highly efficient oil/water separation materials have brought much attention. It requests superhydrophobic surfaces with a rapid and facile separation process, excellent durability, and large-scale fabrication. Herein, a facile vapor-liquid sol-gel, and free radical polymerization reaction method to prepare the durable and robust superhydrophobic cotton fabric is proposed. Moreover, the fabric can be used for highly efficient and various oil/water separation. It is prepared via a simple two-step process, including a vapor-liquid sol-gel process to deposit with thiols particles, and then followed a free radical polymerization reaction to graft 2,2,3,4,4,4-hexafluorobutyl methacrylate. Scanning electron microscopy and Fourier transform infrared spectrometry prove that the rough structures are generated from the hydrolysis condensation reaction between tetraethyl orthosilicate and 3-mercaptopropyltriethoxysilane. As a result, the synthetic chemical composition provided by the natural fabric and silica nanoparticles synergistically construct a superhydrophobic surface with water contact angles and shedding angle of 158° and 9°, respectively. Additionally, the treated fabric exhibits excellent chemical resistance and self-cleaning ability. Remarkably, the fabric still retains superhydrophobic and excellent mechanical robustness after 30 cycles of various oil/water separation. In summary, the resultant fabrics with excellent chemical resistance, remarkable mechanical robustness, and versatile separation abilities have potential applications in various oil/water separations.     

水泥窑低温有机朗肯循环联合发电技术

以某一新型二代水泥技术的7 000 t/d熟料生产线为例,单纯的采用汽水朗肯循环,存在热量回收不彻底,部分低品位余热资源无法有效回收等问题。采用汽水朗肯循环及有机朗肯循环联合发电系统的方案,结果表明：联合朗肯循环系统发电功率提高了614 kW,吨熟料发电量增加了2.1 kWh/kg,提高了8%;净发电功率提高了511 kW,净发电量实际提高了7.1%,提高了水泥余热回收的效率。     

快淬工艺对无钴AB5型贮氢合金循环稳定性的影响

研究了快淬工艺对无钴AB5型LaxMm1-x(NiMnSiAlFe)4.9(x=0,0.45,0.75,1.0)合金微观结构及电化学循环稳定性的影响.结果表明快淬处理显著改善合金的成分均匀性,使晶粒细化,并显著提高合金的循环稳定性.当淬速从0m/s增加到28 m/s时,经300次充放循环后,x=0.45合金的容量衰减率D从0.28 mAh/g·c-1(c代表一次循环)下降到0.13mAh/g·c-1;x=1.0合金的容量衰减率D从0.3mAh/g·c-1下降到0.14mAh/g·c-1.