CDK5RAP3, an essential regulator of checkpoint,interacts with RPL26 and maintains the stability of cell growth

Purpose and MaterialsCDK5RAP3 (CDK5 regulatory subunit associated protein 3) was originally identified as a binding protein of CDK5. It is a crucial gene controlling biological functions, such as cell proliferation, apoptosis, invasion, and metastasis. Although previous studies have also shown that CDK5RAP3 is involved in a variety of signalling pathways, however, the mechanism of CDK5RAP3 remains largely undefined. This study utilized MEFs from conditional knockout mice to inhibit CDK5RAP3 and knockdown CDK5RAP3 in MCF7 to explore the role of CDK5RAP3 in cell growth, mitosis, and cell death.ResultsCDK5RAP3 was found to be widely distributed throughout the centrosome, spindle, and endoplasmic reticulum, indicating that it is involved in regulating a variety of cellular activities. CDK5RAP3 deficiency resulted in instability of cell growth. CDK5RAP3 deficiency partly blocks the cell cycle in G₂/M by downregulating CDK1 (Cyclin‐dependent kinase 1) and CCNB1 (Cyclin B1) expression levels. The cell proliferation rate was decreased, thereby slowing down the cell growth rate. Furthermore, the results showed that CDK5RAP3 interacts with RPL26 (ribosome protein L26) to regulate the mTOR pathway. CDK5RAP3 and RPL26 deficiency inhibited mTOR/p‐mTOR protein and induce autophagy, resulting in an upregulation of the percentage of apoptosis, and the upregulated percentage of apoptosis also slowed cell growth.ConclusionsOur experiments show that CDK5RAP3 interacts with RPL26 and maintains the stability of cell growth. It shows that CDK5RAP3 plays an important role in cell growth and can be used as the target of gene medicine.

In normal, CDK5RAP3 is distributed in the centrosome, spindle and endoplasmic reticulum, the cells undergoes the growth and proliferation. However, when CDK5RAP3 is deficient, the cell cycle is blocked in G₂/M and cell proliferation slows down, and the partial cycle block does not cause apoptosis. Additionally, CDK5RAP3 distributed in the endoplasmic reticulum combined with the deficiency of RPL26 will inhibit the mTOR pathway, aggravate autophagy and trigger apoptosis.     

核不均一核糖核蛋白R基因沉默抑制非小细胞肺癌细胞恶性转化

核不均一核糖核蛋白R(hnRNPR)是一种与mRNA生物学功能密切相关的RNA结合蛋白质,与多种肿瘤细胞的恶性转化相关。然而,在非小细胞肺癌(NSCLC)中的作用机制尚不清楚。本研究通过检索公共数据库发现,hnRNPR蛋白主要在肺癌细胞核中表达,hnRNPR mRNA在非小细胞肺癌组织中高表达,并且与肺腺癌患者的生存率呈负相关;hnRNPR的表达与非小细胞肺癌患者的性别、T分期显著相关(P<0.05)。构建hnRNPR基因沉默的非小细胞肺癌稳定细胞株,检测细胞功能变化,结果显示,hnRNPR基因沉默抑制了细胞增殖、迁移和侵袭能力以及上皮-间质转化(EMT),并将细胞周期阻滞在G₁期(P<0.01)。生物信息学分析显示,非小细胞肺癌中hnRNPR基因与9 310个基因的表达正相关(皮尔逊相关系数>0,P<0.05),与10 680个基因的表达负相关(皮尔逊相关系数<0,P<0.05)。综上所述,hnRNPR在非小细胞肺癌中高表达,可能作为剪接体的组分,通过调节相关基因的表达,促进了NSCLC细胞的恶性转化。     

准噶尔荒漠大翅霸王的生殖物候及结实格局

大翅霸王是多年生早春开花草本植物,是准噶尔荒漠地区的建群种之一。对野生大翅霸王的生殖物候、果实形态、结实格局和种子萌发特性进行了研究。结果表明:(1)大翅霸王的营养期生长期为20—30d,占整个生活周期的1/4,生殖生长期长约90—100d,其中花期约占1/2,果熟期短;(2)大翅霸王种群能产生3种形态的果实,可将植株分为5翅型、4/5翅型和3/4/5翅型植株,它们分别占种群植株数的3.45%、83.15%和13.40%。(3)依据个体大小的变化,3种类型果实在植株上的比例发生了显著变化。随植株个体的增大,三翅果所占比例逐渐增多,由0增加到2.65%;四翅果所占比例也增多,但在二级个体上有最大比例17.01%;五翅果实所占比例最高(80%)且没有显著变化。(4)三翅果、四翅果和五翅果内种子形态无差异,萌发率均小于30%;划破种皮能不同程度的加速和促进种子的萌发。大翅霸王特有的生殖物候和果实的表型多样性是其对荒漠干旱地区恶劣多变环境长期适应的结果。     

一株产絮凝剂不动杆菌的筛选及其絮凝特性

从活性污泥中筛选出一株高效的微生物絮凝剂产生菌,鉴定为鲍曼不动杆菌.蚕豆根尖细胞微核试验未显示该菌株所产絮凝剂具有遗传毒性.该菌产絮凝剂的最佳碳源和氮源分别为葡萄糖和酵母浸出汁,培养时间为24 h.在絮凝体系中加入Ca2 能明显提高发酵液的絮凝率.在pH为8.0时对高岭土悬浊液和污水具有良好的絮凝效果.     

种植年限对寿光设施大棚土壤生态环境的影响

为探讨不同种植年限对设施大棚土壤生态环境的影响,研究了不同种植年限的大棚土壤物理性状、化学性状以及微生物区系的差异变化,并对种植年限与土壤理化性状和微生物数量之间的相关性进行了统计分析。结果表明,随种植年限增加,土壤容重和pH值均明显下降,而土壤孔隙度、土壤EC值和土壤盐分含量则显著升高,有机质含量也呈增长的趋势;土壤全氮和全磷量均持续升高,土壤全钾、硝态氮和速效钾均先升高后降低;随着设施大棚种植年限的增长,细菌数量先上升后下降,放线菌数量先迅速升高后保持相对稳定,只有真菌数量呈持续增加的趋势。这说明由于大量的有机无机肥料投入,种植年限不同的设施大棚土壤均出现一定酸化现象,养分失衡,微生态平衡遭到破坏,盐分含量显著升高,存在明显的环境风险。应提倡合理科学施肥,以保证设施大棚土壤的生态环境安全。     

浙江省森林信息提取及其变化的空间分布

如何利用遥感技术提取森林信息是遥感应用的重要领域之一。以不同时相的Landsat TM/ETM+为数据源,采用面向对象和基于多级决策树的分类方法得到浙江省2000年、2005年以及2010年的森林植被覆被图。经实地采样点验证,2010年分类精度达到92.76%,精度满足要求。介绍了浙江森林信息的快速提取方法,即统计不同森林类型的Landsat TM影像原始波段和LBV变换值以及各种植被指数在各时相上的差异,经过C5决策树训练,选取合适的规则和阈值实现森林信息的提取。结果表明,面向对象分割与决策树算法结合可以作为森林信息提取的有效方法。最后,通过对3期森林专题图进行空间叠加分析,得到了森林资源动态变化的空间分布,并以此为基础对林地变化的类型及原因进行分析,结果显示浙江省森林资源变化主要分布在浙西北山区、浙中南山区以及沿海地带,这一结果可以为有关部门的决策提供依据。     

基于VAR模型的森林植被碳储量影响因素分析——以陕西省为例

森林作为陆地生态系统最大的碳库,对现在及未来的气候变化、碳平衡都具有重要影响。而对影响森林植被碳库的自然和非自然因素进行研究更是对增强森林的碳汇作用,继而改善生态环境状况意义重大。现有的森林动态模型虽然可以很好的模拟碳储量各影响因子之间的联系,但研究往往集中于小尺度从单一影响因素着手,且由于确定模型输入变量和参数的复杂性,使得这些模型在区域甚至更大尺度上的应用存在着一些困难。因此,运用VAR模型,以陕西省为例,构建森林植被碳储量与病虫害发生面积、木材产量、森林火灾面积、森林抚育面积、人工更新造林面积、降水和温度之间的动态关系,来验证该模型在省级尺度条件下的区域森林植被碳储量影响因素分析中的可行性。结果表明:各变量在5%的显著性水平下呈一阶单整序列并具有长期稳定的均衡关系,VAR模型也通过了平稳性检验满足运行的前提条件。通过脉冲响应和方差分解分析可知,森林病虫害、木材产量对陕西省森林植被碳储量呈现出很明显的负作用,并且贡献度很高,分别为5.61%和4.52%;森林抚育、人工更新造林对碳储量的影响存在一定的滞后期;火灾、温度和降水的冲击给碳储量带来的影响均不明显。模型较好的模拟了各影响因素对陕西省碳储量的影响,且具有一定的现实意义,因此,该模型可应用于省级尺度条件下的区域森林植被碳储量影响因素分析。     

SARS-CoV-2 envelope protein causes acute respiratory distress syndrome (ARDS)-like pathological damages and constitutes an antiviral target

Cytokine storm and multi-organ failure are the main causes of SARS-CoV-2-related death. However, the origin of excessive damages caused by SARS-CoV-2 remains largely unknown. Here we show that the SARS-CoV-2 envelope (2-E) protein alone is able to cause acute respiratory distress syndrome (ARDS)-like damages in vitro and in vivo. 2-E proteins were found to form a type of pH-sensitive cation channels in bilayer lipid membranes. As observed in SARS-CoV-2-infected cells, heterologous expression of 2-E channels induced rapid cell death in various susceptible cell types and robust secretion of cytokines and chemokines in macrophages. Intravenous administration of purified 2-E protein into mice caused ARDS-like pathological damages in lung and spleen. A dominant negative mutation lowering 2-E channel activity attenuated cell death and SARS-CoV-2 production. Newly identified channel inhibitors exhibited potent anti-SARS-CoV-2 activity and excellent cell protective activity in vitro and these activities were positively correlated with inhibition of 2-E channel. Importantly, prophylactic and therapeutic administration of the channel inhibitor effectively reduced both the viral load and secretion of inflammation cytokines in lungs of SARS-CoV-2-infected transgenic mice expressing human angiotensin-converting enzyme 2 (hACE-2). Our study supports that 2-E is a promising drug target against SARS-CoV-2.Subject terms: Cell death, Molecular biology