Intraspecific molecular variation inHieracium sect.Alpina (Asteraceae), an apomictic group

Intraspecific variation of four agamospecies ofHieracium sect.Alpina was studied using RAPD and isozyme techniques. No variation in either multiprimer RAPD or multi-enzyme phenotypes was observed withinH. holosericeum, suggesting that this widespread species consists of only a single genotype. A low level of within-population isozyme variation was seen inH. tenuifrons andH. calenduliflorum, the origin of which appears to be consistent with somatic mutation. Most isozyme and all RAPD variation in these two species was partitioned between populations. A strong correlation with geography suggests that its cause may be due to polytopic (-polyphyletic?) origin or perhaps to mutation and dispersal. The most variable species wasH. alpinum, in which isozyme variation occurred mostly within populations rather than between them, suggesting occasional sexual events or that the parents ofH. alpinum were heterozygous. RAPD variation in this species, in contrast, was partitioned between Scottish and Swiss populations, suggesting the existence of geographical races.     

A new metabolic pathway from n-dodecane to α, ω-dodecanedioic acid in a mutant of Candida tropicalis

Summary The metabolic formation of ,-dodecanedioic acid via ,-dodecanediol from n-dodecane using a mutant S76 of Candida tropicalis was studied.It was found that resting cells of S76 produce ,-dodecanediol from n-dodecane. This intermediate was identified by different analytical methods. With n-dodecanol as substrate the quantitative changes in the concentrations of ,-dodecanediol as well as other intermediates, e.g. monoacid, -hydroxy acid and ,-dioic acid produced by resting cells of S76 for different periods of time were determined. With ,-dodecanediol as the sole carbon source, quantitative changes of -hydroxy acid and ,-dioic acid produced by S76 were also recorded.The results confirm the existence of a new metabolic pathway via ,-diol in the course of ,-dioic acid formation from n-alkane in the mutant S76 of C. tropicalis.     

Chromosome-level genome assembly and characterization of Sophora Japonica

Sophora japonica is a medium-size deciduous tree belonging to Leguminosae family and famous for its high ecological, economic and medicinal value. Here, we reveal a draft genome of S. japonica, which was ∼511.49 Mb long (contig N50 size of 17.34 Mb) based on Illumina, Nanopore and Hi-C data. We reliably assembled 110 contigs into 14 chromosomes, representing 91.62% of the total genome, with an improved N50 size of 31.32 Mb based on Hi-C data. Further investigation identified 271.76 Mb (53.13%) of repetitive sequences and 31,000 protein-coding genes, of which 30,721 (99.1%) were functionally annotated. Phylogenetic analysis indicates that S. japonica separated from Arabidopsis thaliana and Glycine max ∼107.53 and 61.24 million years ago, respectively. We detected evidence of species-specific and common-legume whole-genome duplication events in S. japonica. We further found that multiple TF families (e.g. BBX and PAL) have expanded in S. japonica, which might have led to its enhanced tolerance to abiotic stress. In addition, S. japonica harbours more genes involved in the lignin and cellulose biosynthesis pathways than the other two species. Finally, population genomic analyses revealed no obvious differentiation among geographical groups and the effective population size continuously declined since 2 Ma. Our genomic data provide a powerful comparative framework to study the adaptation, evolution and active ingredients biosynthesis in S. japonica. More importantly, our high-quality S. japonica genome is important for elucidating the biosynthesis of its main bioactive components, and improving its production and/or processing.     

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     

生物启发的细菌表面人造矿物壳:通过仿生矿化保护活细胞

【目的】生物启发的细菌表面仿生矿化人造矿物壳被用于保护活细胞。【方法】将细菌限制在坚固而完整的矿物壳中,有限的物理空间和物质交换使其暂时进行休眠,降低长期保存期间的活力损失以及提高在各种极端环境中的生存能力,并且能够通过酸去除矿物壳而重新激活细菌。【结果】相较于未仿生矿化的细菌(EcN),矿化细菌(EcN@CaCO₃)在32 d的储存实验中活力最高提升262倍;在pH 2.5的强酸环境中存活率提高837倍;在pH 12.0的强碱环境中存活率提高171倍;在80 ℃的高温条件下存活率提高59.1倍;甚至在抗生素溶液中,EcN@CaCO₃中细菌的存活率是EcN的729.7倍。【结论】本研究利用仿生矿化提高了细菌的保存稳定性,使其能在酸刺激下去除涂层恢复活性,也能在极端环境下保留细菌的活力,为微生物在环境生态、食品制造和生物医药等领域的应用提供研究基础。     

Friend or Foe? Implication of the autophagy-lysosome pathway in SARS-CoV-2 infection and COVID-19

There is increasing amount of evidence indicating the close interplays between the replication cycle of SARS-CoV-2 and the autophagy-lysosome pathway in the host cells. While autophagy machinery is known to either assist or inhibit the viral replication process, the reciprocal effects of the SARS-CoV-2 on the autophagy-lysosome pathway have also been increasingly appreciated. More importantly, despite the disappointing results from the clinical trials of chloroquine and hydroxychloroquine in treatment of COVID-19, there is still ongoing effort in discovering new therapeutics targeting the autophagy-lysosome pathway. In this review, we provide an update-to-date summary of the interplays between the autophagy-lysosome pathway in the host cells and the pathogen SARS-CoV-2 at the molecular level, to highlight the prognostic value of autophagy markers in COVID-19 patients and to discuss the potential of developing novel therapeutic strategies for COVID-19 by targeting the autophagy-lysosome pathway. Thus, understanding the nature of such interactions between SARS-CoV-2 and the autophagy-lysosome pathway in the host cells is expected to provide novel strategies in battling against this global pandemic.     

Caveolin-1 identified as a key mediator of acute lung injury using bioinformatics and functional research

Acute lung injury (ALI) is a potentially life-threatening, devastating disease with an extremely high rate of mortality. The underlying mechanism of ALI is currently unclear. In this study, we aimed to confirm the hub genes associated with ALI and explore their functions and molecular mechanisms using bioinformatics methods. Five microarray datasets available in GEO were used to perform Robust Rank Aggregation (RRA) to identify differentially expressed genes (DEGs) and the key genes were identified via the protein-protein interaction (PPI) network. Lipopolysaccharide intraperitoneal injection was administered to establish an ALI model. Overall, 40 robust DEGs, which are mainly involved in the inflammatory response, protein catabolic process, and NF-κB signaling pathway were identified. Among these DEGs, we identified two genes associated with ALI, of which the CAV-1/NF-κB axis was significantly upregulated in ALI, and was identified as one of the most effective targets for ALI prevention. Subsequently, the expression of CAV-1 was knocked down using AAV-shCAV-1 or CAV-1-siRNA to study its effect on the pathogenesis of ALI in vivo and in vitro. The results of this study indicated that CAV-1/NF-κB axis levels were elevated in vivo and in vitro, accompanied by an increase in lung inflammation and autophagy. The knockdown of CAV-1 may improve ALI. Mechanistically, inflammation was reduced mainly by decreasing the expression levels of CD3 and F4/80, and activating autophagy by inhibiting AKT/mTOR and promoting the AMPK signaling pathway. Taken together, this study provides crucial evidence that CAV-1 knockdown inhibits the occurrence of ALI, suggesting that the CAV-1/NF-κB axis may be a promising therapeutic target for ALI treatment.Subject terms: Cell signalling, Respiratory tract diseases     

Age‐related memory vulnerability to interfering stimuli is caused by gradual loss of MAPK‐dependent protection in Drosophila

Age‐related memory impairment (AMI) is a common phenomenon across species. Vulnerability to interfering stimuli has been proposed to be an important cause of AMI. However, the molecular mechanisms underlying this vulnerability‐related AMI remain unknown. Here we show that learning‐activated MAPK signals are gradually lost with age, leading to vulnerability‐related AMI in Drosophila. Young flies (2‐ or 3‐day‐old) exhibited a significant increase in phosphorylated MAPK levels within 15 min after learning, whereas aged flies (25‐day‐old) did not. Compared to 3‐day‐old flies, significant 1 h memory impairments were observed in 15‐, 20‐, and 30‐day‐old flies, but not in 10‐day‐old flies. However, with post‐learning interfering stimuli such as cooling or electric stimuli, 10‐day‐old flies had worse memory performance at 1 h than 3‐day‐old flies, showing a premature AMI phenomenon. Increasing learning‐activated MAPK signals through acute transgene expression in mushroom body (MB) neurons restored physiological trace of 1 h memory in a pair of MB output neurons in aged flies. Decreasing such signals in young flies mimicked the impairment of 1 h memory trace in aged flies. Restoring learning‐activated MAPK signals in MB neurons in aged flies significantly suppressed AMI even with interfering stimuli. Thus, our data suggest that age‐related loss of learning‐activated neuronal MAPK signals causes memory vulnerability to interfering stimuli, thereby leading to AMI.