OsMre11 Is Required for Mitosis during Rice Growth and Development

Meiotic recombination 11 (Mre11) is a relatively conserved nuclease in various species. Mre11 plays important roles in meiosis and DNA damage repair in yeast, humans and Arabidopsis, but little research has been done on mitotic DNA replication and repair in rice. Here, it was found that Mre11 was an extensively expressed gene among the various tissues and organs of rice, and loss-of-function of Mre11 resulted in severe defects of vegetative and reproductive growth, including dwarf plants, abnormally developed male and female gametes, and completely abortive seeds. The decreased number of cells in the apical meristem and the appearance of chromosomal fragments and bridges during the mitotic cell cycle in rice mre11 mutant roots revealed an essential role of OsMre11. Further research showed that DNA replication was suppressed, and a large number of DNA strand breaks occurred during the mitotic cell cycle of rice mre11 mutants. The expression of OsMre11 was up-regulated with the treatment of hydroxyurea and methyl methanesulfonate. Moreover, OsMre11 could form a complex with OsRad50 and OsNbs1, and they might function together in non-homologous end joining and homologous recombination repair pathways. These results indicated that OsMre11 plays vital roles in DNA replication and damage repair of the mitotic cell cycle, which ensure the development and fertility of rice by maintaining genome stability.     

Platelet-Rich Plasma Promotes the Proliferation of Human Keratinocytes via a Progression of the Cell Cycle. A Role of Prolidase

Although the role of platelet-rich plasma (PRP) in tissue regeneration has been confirmed in many studies, the mechanism of this process is still not fully understood. Human keratinocytes (HaCaT) cells were used as an experimental model for studies on the effects of PRP on cell proliferation, migration, collagen biosynthesis, prolidase activity, and its expression and anabolic signaling. The activation of epidermal growth factor receptor (EGFR), β₁-integrin, and insulin-like growth factor-1 receptor (IGF-1R) by PRP were investigated by western blot and immunocytochemistry. It has been found that PRP induced keratinocytes migration and proliferation through activation of cell cycle progression and EGFR downstream signaling. Similar biological effects were achieved by an addition to the culture medium of prolidase (PEPD), a ligand of EGFR (PRP is a rich source of PEPD–2 ng/mL). PRP-dependent stimulation of collagen biosynthesis was accompanied by an increase in the expression of NF-κβ, IGF-1R-downstream signaling proteins, and PEPD activity. The data suggest that PRP activates a complex of growth factors and adhesion receptors that stimulate cell proliferation, migration, and collagen biosynthesis. PRP induces PEPD-dependent human keratinocyte proliferation through activation of the EGFR receptor. Our study provides a novel mechanism of PRP-dependent wound healing.     

Inhibitors of Cyclin-Dependent Kinases: Types and Their Mechanism of Action

Recent studies on cyclin-dependent kinase (CDK) inhibitors have revealed that small molecule drugs have become very attractive for the treatment of cancer and neurodegenerative disorders. Most CDK inhibitors have been developed to target the ATP binding pocket. However, CDK kinases possess a very similar catalytic domain and three-dimensional structure. These features make it difficult to achieve required selectivity. Therefore, inhibitors which bind outside the ATP binding site present a great interest in the biomedical field, both from the fundamental point of view and for the wide range of their potential applications. This review tries to explain whether the ATP competitive inhibitors are still an option for future research, and highlights alternative approaches to discover more selective and potent small molecule inhibitors.     

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。     

弧焊电源的焊接电流、负载持续率和发热试验

详细分析了弧焊电源不同负载持续率下的焊接电流折算关系、发热试验电源热时间常数的测定。对发热试验中容易被忽视、但会造成较大的系统误差的问题提出了注意点和相应的解决办法。     

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。