Cryo-EM structure of the fatty acid reductase LuxC–LuxE complex provides insights into bacterial bioluminescence

The discovery of reduced flavin mononucleotide and fatty aldehydes as essential factors of light emission facilitated study of bacterial luminescence. Although the molecular mechanisms underlying bacterial luminescence have been studied for more than 60 years, the structure of the bacterial fatty acid reductase complex remains unclear. Here, we report the cryo-EM structure of the Photobacterium phosphoreum fatty acid reductase complex LuxC–LuxE to a resolution of 2.79 Å. We show that the active site Lys238/Arg355 pair of LuxE is >30 Å from the active site Cys296 of LuxC, implying that catalysis relies on a large conformational change. Furthermore, mutagenesis and biochemical experiments support that the L-shaped cleft inside LuxC plays an important role in substrate binding and reaction. We obtained a series of mutants with significantly improved activity as measured by in vitro bioluminescence assays and demonstrated that the double mutant W111A/F483K displayed the highest activity (370% of the WT). Our results indicated that the activity of LuxC significantly affects the bacterial bioluminescence reaction. Finally, we expressed this mutated lux operon in Escherichia coli but observed that the in vivo concentrations of ATP and NADPH limited the enzyme activity; thus, we conclude that the luminous intensity mainly depends on the level of metabolic energy.     

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     

TEB/POLQ plays dual roles in protecting Arabidopsis from NO-induced DNA damage

Nitric oxide (NO) is a key player in numerous physiological processes. Excessive NO induces DNA damage, but how plants respond to this damage remains unclear. We screened and identified an Arabidopsis NO hypersensitive mutant and found it to be allelic to TEBICHI/POLQ, encoding DNA polymerase θ. The teb mutant plants were preferentially sensitive to NO- and its derivative peroxynitrite-induced DNA damage and subsequent double-strand breaks (DSBs). Inactivation of TEB caused the accumulation of spontaneous DSBs largely attributed to endogenous NO and was synergistic to DSB repair pathway mutations with respect to growth. These effects were manifested in the presence of NO-inducing agents and relieved by NO scavengers. NO induced G2/M cell cycle arrest in the teb mutant, indicative of stalled replication forks. Genetic analyses indicate that Polθ is required for translesion DNA synthesis across NO-induced lesions, but not oxidation-induced lesions. Whole-genome sequencing revealed that Polθ bypasses NO-induced base adducts in an error-free manner and generates mutations characteristic of Polθ-mediated end joining. Our experimental data collectively suggests that Polθ plays dual roles in protecting plants from NO-induced DNA damage. Since Polθ is conserved in higher eukaryotes, mammalian Polθ may also be required for balancing NO physiological signaling and genotoxicity.     

云南主要有害实蝇种类及区划

采用诱剂诱捕辅以受害瓜果调查的方法,系统梳理了云南有害实蝇类群,确定主要有害种类25种。基于云南自然地理特征,采用聚类分析法深入探讨了云南实蝇区系,提出云南实蝇地理区划可分为德宏、版纳盆谷区,南部边缘中低山宽谷区,滇西南山原峡谷区,中东部高原、岩溶山原区以及北部高原山地区等5大区域。研究发现,受热量条件制约,云南主要有害实蝇类群呈南北向梯度递减;受纵向岭谷区"通道-阻隔"综合作用影响,云南西南部河谷地区是实蝇危害较为严重的区域。首次系统揭示了云南主要有害实蝇的地理分布规律。     

Rapid improvement of rice eating and cooking quality through gene editing toward glutelin as target

Rice eating and cooking quality(ECQ) is a major concern of breeders and consumers, determining market competitiveness worldwide. Rice grain protein content(GPC) is negatively related to ECQ,making it possible to improve ECQ by manipulating GPC. However, GPC is genetically complex and sensitive to environmental conditions; therefore, little progress has been made in traditional breeding for ECQ. Here, we report that CRISPR/Cas9-mediated knockout of genes encoding the grain storage protein gluteli...     

High auxin stimulates callus through SDG8-mediated histone H3K36 methylation in Arabidopsis

Callus induction,which results in fate transition in plant cells,is considered as the first and key step for plant regeneration.This process can be stimulated in different tissues by a callus-inducing medium(CIM),which contains a high concentration of phytohormone auxin.Although a few key regulators for callus induction have been identified,the multiple aspects of the regulatory mechanism driven by high levels of auxin still need further investigation.Here,we find that high auxin induces callus ...     

呼伦贝尔草原沙狐洞穴的结构

沙狐（Vulpes corsac）又名东沙狐,属食肉目犬科,主要分布在亚洲中部的草原、荒漠和半荒漠地带,在我国主要分布在内蒙古、甘肃、宁夏和新疆部分地区。由于沙狐主要以鼠类为食,因此沙狐在调节鼠类数量和控制鼠害方面起着重要的作用（马逸清等,1986）。《中国物种红色名录》（汪松和解焱,2004）将沙狐列为“易危”,指出其“数据缺乏”。     

中微量元素和有益元素对水稻生长和吸收镉的影响

采用盆栽试验,研究了中微量元素和有益元素对水稻生长和吸收镉的影响。结果表明,在所有测试的元素和施用方法中,硅酸钠叶面喷施显著增加稻谷产量,而碳酸钙、硼酸、硅酸钠土施和亚硒酸钠显著降低了稻谷产量。镁、锌、铁的盐酸盐形态对水稻籽粒的增产效果优于硫酸盐形态,而钙、铜的硫酸盐形态增产效果略高于盐酸盐形态。在钙、镁、硫三种中量元素中,钙增加了水稻籽粒中的Cd浓度和吸收量,而镁和硫则降低了籽粒中的Cd浓度和吸收量,以硫磺粉处理为最低。稻草中的Cd浓度和总量均以氯化镁处理为最高,硫磺粉处理最低。镁能有效抑制Cd从秸秆向籽粒的转移,其盐酸盐优于硫酸盐。在微量元素中,锌对水稻Cd的吸收抑制作用最为显著,其次是铜,而有益元素肥料硅酸钠叶面喷施则显著增加了稻谷中的Cd浓度和吸收量。硫酸亚铁、氯化锰、氯化铜、硼酸和硼砂处理都能有效地抑制Cd从秸秆向籽粒的转移,而硅酸钠叶面喷施和锌处理则促进了Cd的转移,表明硅酸钠抑制水稻吸收Cd的机制很可能发生在土壤中,而非在植株体内或地上部分。在Cd污染土壤上选用适宜的中微量和有益元素肥料及其施用方法,能有效降低水稻对镉的吸收和稻米中的Cd含量。     

皮层神经发生的分子调控机制

在高等动物神经发育过程中,背侧端脑神经上皮细胞在多种调控基因及环境调控因子的作用下经历了错综复杂的发育事件,逐步形成具有精细的分层结构和高级功能的神经皮层。这些发育中的调控具有严格的时间和区域特性。本文主要就皮层形成中神经干细胞增殖、分化方向及皮层神经元亚型的特化等方面的调控机制予以论述。     

Circular RNA circ‐RCCD promotes cardiomyocyte differentiation in mouse embryo development via recruiting YY1 to the promoter of MyD88

Congenital heart disease (CHD) is the most common birth defect, affecting approximately 1% of live births. Genetic and environmental factors are leading factors to CHD, but the mechanism of CHD pathogenesis remains unclear. Circular RNAs (circRNAs) are kinds of endogenous non‐coding RNAs (ncRNAs) involved in a variety of physiological and pathological processes, especially in heart diseases. In this study, three significant differently expressed circRNA between maternal embryonic day (E) E13 and E17 was found by microarray assay. Among them, the content of circ‐RCCD increases with the development of heart and was enriched in primary cardiomyocytes of different species, which arouses our attention. Functional experiments revealed that inhibition of circ‐RCCD dramatically suppressed the formation of beating cell clusters, the fluorescence intensity of cardiac differentiation marker MF20, and the expression of the myocardial‐specific markers CTnT, Mef2c, and GATA4. Next, we found that circ‐RCCD was involved in cardiomyocyte differentiation through negative regulation of MyD88 expression. Further experiments proved that circ‐RCCD inhibited MyD88 levels by recruiting YY1 to the promoter of MyD88; circ‐RCCD inhibited nuclear translocation of YY1. These results reported that circ‐RCCD promoted cardiomyocyte differentiation by recruiting YY1 to the promoter of MyD88. And, this study provided a potential role and molecular mechanism of circ‐RCCD as a target for the treatment of CHD.