The glucose metabolite methylglyoxal inhibits expression of the glucose transporter genes by inactivating the cell surface glucose sensors Rgt2 and Snf3 in yeast

Methylglyoxal (MG) is a cytotoxic by-product of glycolysis. MG has inhibitory effect on the growth of cells ranging from microorganisms to higher eukaryotes, but its molecular targets are largely unknown. The yeast cell-surface glucose sensors Rgt2 and Snf3 function as glucose receptors that sense extracellular glucose and generate a signal for induction of expression of genes encoding glucose transporters (HXTs). Here we provide evidence that these glucose sensors are primary targets of MG in yeast. MG inhibits the growth of glucose-fermenting yeast cells by inducing endocytosis and degradation of the glucose sensors. However, the glucose sensors with mutations at their putative ubiquitin-acceptor lysine residues are resistant to MG-induced degradation. These results suggest that the glucose sensors are inactivated through ubiquitin-mediated endocytosis and degraded in the presence of MG. In addition, the inhibitory effect of MG on the glucose sensors is greatly enhanced in cells lacking Glo1, a key component of the MG detoxification system. Thus the stability of these glucose sensors seems to be critically regulated by intracellular MG levels. Taken together, these findings suggest that MG attenuates glycolysis by promoting degradation of the cell-surface glucose sensors and thus identify MG as a potential glycolytic inhibitor.     

Identification of compound heterozygous DNAH11 variants in a Han-Chinese family with primary ciliary dyskinesia

Primary ciliary dyskinesia (PCD) is a group of genetically and clinically heterogeneous disorders with motile cilia dysfunction. It is clinically characterized by oto-sino-pulmonary diseases and subfertility, and half of the patients have situs inversus (Kartagener syndrome). To identify the genetic cause in a Han-Chinese pedigree, whole-exome sequencing was conducted in the 37-year-old proband, and then, Sanger sequencing was performed on available family members. Minigene splicing assay was applied to verify the impact of the splice-site variant. Compound heterozygous variants including a splice-site variant (c.1974-1G>C, rs1359107415) and a missense variant (c.7787G>A, p.(Arg2596Gln), rs780492669), in the dynein axonemal heavy chain 11 gene (DNAH11) were identified and confirmed as the disease-associated variants of this lineage. The minigene expression in vitro revealed that the c.1974-1G>C variant could cause skipping over exon 12, predicted to result in a truncated protein. This discovery may enlarge the DNAH11 variant spectrum of PCD, promote accurate genetic counselling and contribute to PCD diagnosis.     

Carbonyl stress: malondialdehyde induces damage on rat hippocampal neurons by disturbance of Ca<Superscript>2+</Superscript> homeostasis

The objective of this study was to investigate the influences of carbonyl stress induced by malondialdehyde (MDA), a typical intermediate of lipid peroxidation, on intracellular free Ca²⁺ concentration ([Ca²⁺]_i) alterations in cultured hippocampal neurons of rat. The microphotographic study clearly demonstrated that the hippocampal neurons became gradually damaged following exposure to different concentrations of MDA. Further study indicated that the plasma membrane Ca²⁺-ATPase (PMCA) activity was inhibited by MDA in a concentration- and time-dependent manner. The supplementation of 100 μM MDA was found to cause a notable early phase increase of [Ca²⁺]_i in hippocampal neuron cultures followed by a more pronounced late-phase elevation of [Ca²⁺]_i. Such effect of MDA was prevented by the addition of nimodipine, an inhibitor of L-type calcium channel or by an extracellular Ca²⁺ chelator EGTA. The identification of the calcium signalling pathways were studied by applying U73122, an inhibitor of PL-C, and H-89, an inhibitor of protein kinase A (PKA), showing the involvement of PL-C/IP3 pathway but not the PKA/cAMP pathway. These results suggested that MDA-related carbonyl stress caused damages of rat hippocampal neurons by triggering Ca²⁺ influx and influencing Ca²⁺ homeostasis in cultured neurons, and also MDA may act as a signalling molecule regulating Ca²⁺ release from intracellular stores.     

荧光物示踪法定量测定水稻-叶蝉-蜘蛛食物链的营养关系

首次采用稀土元素铕荧光物示踪法,对水稻－叶蝉－蜘蛛这一食物链营养关系进行了初步的定量测试,结果表明,所选用的稀土元素铕可以通过该食物链而传递,证明铕用于食物链营养关系定量分析是可行的,早稻孕穗期,晚稻分薛期施铕7d后,其含铕量均表现为叶片＞茎及叶鞘;根据叶蝉取食水稻后测定的含铕量和叶蝉体重的不同进行折算,每100头叶蝉每天可取食水稻0．71－1．13g;根据拟水狼蛛,锥腹肖蛸,食虫沟瘤蛛捕食叶蝉后含铕量计算,每头拟不狼蛛,锥腹肖蛸,食虫沟瘤蛛平均每天捕食叶蝉分别为4．63头,2．81头,1．0头,捕食能力,拟水狼蛛＞锥腹肖蛸＞食虫沟瘤蛛。     

High regional genetic differentiation of an endangered relict plant Craigia yunnanensis and implications for its conservation

Of the genus Craigia, widespread in the Tertiary, only two relict species survived to modern times. One species is now possibly extinct and the other one, Craigia yunnanensis, is severely endangered. Extensive surveys have located six C. yunnanensis populations in Yunnan province, southwest China. Using fluorescent amplified fragment length polymorphism (AFLP), the genetic diversity and population structure of these populations were examined. It was found that genetic diversity of C. yunnanensis was moderate at the species level, but low at regional and population levels. Analysis of population structure showed significant genetic differentiation between Wenshan and Dehong regions, apparently representing two geographically isolated for long time refuges. There are also clear indications of isolation between populations, which, together with anthropogenically caused decline of population size, will lead to general loss of the species genetic variation with subsequent loss of adaptive potential. To conserve the genetic integrity of C. yunnanensis, we recommend that ex-situ conservation should include representative samples from every population of the two differentiated regions (e.g. Wenshan and Dehong). The crosses between individuals originated from different regions should be avoided because of a high risk of outbreeding depression. As all the extant populations of C. yunnanensis are in unprotected areas with strong anthropogenic impact, there is no alternative to reintroduction of C. yunnanensis into suitable protected locations.     

Evasion of Antiviral Immunity through Sequestering of TBK1/IKKε/IRF3 into Viral Inclusion Bodies

Cells are equipped with pattern recognition receptors (PRRs) such as the Toll-like and RIG-I-like receptors that mount innate defenses against viruses. However, viruses have evolved multiple strategies to evade or thwart host antiviral responses. Viral inclusion bodies (IBs), which are accumulated aggregates of viral proteins, are commonly formed during the replication of some viruses in infected cells, but their role in viral immune evasion has rarely been explored. Severe fever with thrombocytopenia syndrome (SFTS) is an emerging febrile illness caused by a novel phlebovirus in the Bunyaviridae. The SFTS viral nonstructural protein NSs can suppress host beta interferon (IFN-β) responses. NSs can form IBs in infected and transfected cells. Through interaction with tank-binding kinase 1 (TBK1), viral NSs was able to sequester the IKK complex, including IKKε and IRF3, into IBs, although NSs did not interact with IKKε or IRF3 directly. When cells were infected with influenza A virus, IRF3 was phosphorylated and active phosphorylated IRF3 (p-IRF3) was translocated into the nucleus. In the presence of NSs, IRF3 could still be phosphorylated, but p-IRF3 was trapped in cytoplasmic IBs, resulting in reduced IFN-β induction and enhanced viral replication. Sequestration of the IKK complex and active IRF3 into viral IBs through the interaction of NSs and TBK1 is a novel mechanism for viral evasion of innate immunity.     

基于多模态生态治理数据构建生态管理知识图谱技术

我国新时代十年是生态环境保护认识最深、力度最大、举措最实、推进最快、成效最显著的十年。生态环境治理取得成效的同时,管理措施也逐步成熟和规范化,相关生态管理知识成果的文本、视频、照片等多模态数据也日益丰厚。采用先进的知识图谱理念创新我国生态环境保护工作,对未来助力打赢污染防治攻坚战,构建现代环境治理体系具有重要意义。聚焦我国美丽中国和生态文明建设工程领域,将典型污染防治攻坚战、生态恢复工程多模态素材作为数据源,通过数据整合、知识抽取、知识融合后形成标准知识表述,构建生态管理知识图谱体系。具体包括(1)定量分析深圳市"散乱污"企业整治成功案例数据,抽取管理主体、管理对象等实体,挖掘其空间特征、污染特征、治理效果关系;(2)关联分析企业驻点、污染物热点和城市空间相互关系;(3)通过我国典型生态环境损害赔偿案件中的"实施行为-破坏对象-损害功能"特定关系分析,抽取"生态治理行为--受影响环境要素--生态服务提升程度"生态环境管理知识图谱;(4)最终形成了整合"散乱污"治理、生态环境治理行为的综合性生态管理知识图谱,构建了包含12类本体、82个实体,4类、201条关系的图数据库。研究表明,通过污染防治攻坚战成功案例、生态恢复工程成效的多模态数据构建我国生态管理知识图谱,能够形成贴近现实需求的知识体系,有助于依法治污、科学治污和精准治污全过程;也有助于生态环境损害鉴定评估工作中的"多因一果"和"一因多果"分析。建议未来加大生态管理知识图谱的应用,精准识别管理对象、实现科学分析与智能决策,促进公众参与生态管理和加快生态产品价值实现。     

Dynamic tubulation of mitochondria drives mitochondrial network formation

Mitochondria form networks. Formation of mitochondrial networks is important for maintaining mitochondrial DNA integrity and interchanging mitochondrial material, whereas disruption of the mitochondrial network affects mitochondrial functions. According to the current view, mitochondrial networks are formed by fusion of individual mitochondria. Here, we report a new mechanism for formation of mitochondrial networks through KIF5B-mediated dynamic tubulation of mitochondria. We found that KIF5B pulls thin, highly dynamic tubules out of mitochondria. Fusion of these dynamic tubules, which is mediated by mitofusins, gives rise to the mitochondrial network. We further demonstrated that dynamic tubulation and fusion is sufficient for mitochondrial network formation, by reconstituting mitochondrial networks in vitro using purified fusion-competent mitochondria, recombinant KIF5B, and polymerized microtubules. Interestingly, KIF5B only controls network formation in the peripheral zone of the cell, indicating that the mitochondrial network is divided into subzones, which may be constructed by different mechanisms. Our data not only uncover an essential mechanism for mitochondrial network formation, but also reveal that different parts of the mitochondrial network are formed by different mechanisms.     

Characteristics analysis of the complete Wurfbainia villosa chloroplast genome

Physiology and Molecular Biology of Plants - Wurfbainia villosa, which belongs to the huge family Zingiberaceae, is used in the clinic for the treatment of spleen and stomach diseases in southern...