Regulation of mitochondrial NAD pool via NAD+ transporter 2 is essential for matrix NADH homeostasis and ROS production in Arabidopsis

Reactive oxygen species(ROS) play a crucial role in numerous biological processes in plants, including development, responses to environmental stimuli, and programmed cell death(PCD). Deficiency in MOSAIC DEATH 1(MOD1), a plastid-localized enoyl-ACP reductase essential for de novo fatty acid biosynthesis in Arabidopsis thaliana, leads to the increased malate export from chloroplasts to mitochondria, and the subsequent accumulation of mitochondria-generated ROS and PCD. In this study, we report the identification and characterization of a mod1 suppressor, som592. SOM592 encodes mitochondrion-localized NAD~+ transporter 2(NDT2). We show that the mitochondrial NAD pool is elevated in the mod1 mutant. The som592 mutation fully suppressed mitochondrial NADH hyper-accumulation, ROS production, and PCD in the mod1 mutant, indicating a causal relationship between mitochondrial NAD accumulation and ROS/PCD phenotypes. We also show that in wild-type plants, the mitochondrial NAD+uptake is involved in the regulation of ROS production in response to continuous photoperiod. Elevation of the alternative respiration pathway can suppress ROS accumulation and PCD in mod1, but leads to growth restriction. These findings uncover a regulatory mechanism for mitochondrial ROS production via NADH homeostasis in Arabidopsis thaliana that is likely important for growth regulation in response to altered photoperiod.     

Rapid Deamination of Cyclobutane Pyrimidine Dimer Photoproducts at TCG Sites in a Translationally and Rotationally Positioned Nucleosome in Vivo

Sunlight-induced C to T mutation hot spots in skin cancers occur primarily at methylated CpG sites that coincide with sites of UV-induced cyclobutane pyrimidine dimer (CPD) formation. The C and 5-methyl-C in CPDs are not stable and deaminate to U and T, respectively, which leads to the insertion of A by the DNA damage bypass polymerase η, thereby defining a probable mechanism for the origin of UV-induced C to T mutations. Deamination rates for T^mCG CPDs have been found to vary 12-fold with rotational position in a nucleosome in vitro. To determine the influence of nucleosome structure on deamination rates in vivo, we determined the deamination rates of CPDs at TCG sites in a stably positioned nucleosome within the FOS promoter in HeLa cells. A procedure for in vivo hydroxyl radical footprinting with Fe-EDTA was developed, and, together with results from a cytosine methylation protection assay, we determined the translational and rotational positions of the TCG sites. Consistent with the in vitro observations, deamination was slower for one CPD located at an intermediate rotational position compared with two other sites located at outside positions, and all were much faster than for CPDs at non-TCG sites. Photoproduct formation was also highly suppressed at one site, possibly due to its interaction with a histone tail. Thus, it was shown that CPDs of TCG sites deaminate the fastest in vivo and that nucleosomes can modulate both their formation and deamination, which could contribute to the UV mutation hot spots and cold spots.     

Long noncoding RNA lncMREF promotes myogenic differentiation and muscle regeneration by interacting with the Smarca5/p300 complex

Long noncoding RNAs (lncRNAs) play important roles in the spatial and temporal regulation of muscle development and regeneration. Nevertheless, the determination of their biological functions and mechanisms underlying muscle regeneration remains challenging. Here, we identified a lncRNA named lncMREF (lncRNA muscle regeneration enhancement factor) as a conserved positive regulator of muscle regeneration among mice, pigs and humans. Functional studies demonstrated that lncMREF, which is mainly expressed in differentiated muscle satellite cells, promotes myogenic differentiation and muscle regeneration. Mechanistically, lncMREF interacts with Smarca5 to promote chromatin accessibility when muscle satellite cells are activated and start to differentiate, thereby facilitating genomic binding of p300/CBP/H3K27ac to upregulate the expression of myogenic regulators, such as MyoD and cell differentiation. Our results unravel a novel temporal-specific epigenetic regulation during muscle regeneration and reveal that lncMREF/Smarca5-mediated epigenetic programming is responsible for muscle cell differentiation, which provides new insights into the regulatory mechanism of muscle regeneration.     

高脂摄入对小鼠空肠微生物群落结构及功能的损伤

探讨高脂饲养对动物肠道菌群结构及功能的影响。

选择60只8周龄的清洁级雌性KM小鼠, 随机分为3组: 正常饮食组(ND组)、高脂饮食组(HD组)和饥饿组(LD组), 每组20只。预饲期2周, 正饲期4周, 实验结束称重后处死小鼠, 采集小鼠空肠内容物, 采用16S rDNA测序技术分析空肠菌群结构多样性和功能差异。

(1) 不同饲喂方式下各组小鼠体质量变化差异有统计学意义(F=48.859 0, P < 0.05);(2)16S rDNA分析表明, ND组、HD组和LD组小鼠空肠菌群OTUs数量分别为1 218、1 724和1 769个, 其中特有OTUs数量HD组和LD组显著高于ND组, HD组和LD组的Chao1指数和Ace指数显著高于ND组(F=136.747 0、275.740 0, 均P < 0.05);(3)不同饲喂方式下小鼠空肠鉴定出的微生物归为12个门, Bacteroidota和Firmicutes为优势菌门; 丰度大于1%的菌属有17个, 物种注释发现HD组和LD组分别有11个、6个菌属丰度显著增加; 在科水平, Bacteroidaceae和Erysipelotrichaceae在HD组显著高于其他2组(F=5.795 0、154.733 0, 均P < 0.05), Lactobacillaceae和Muribaculaceae在LD组显著高于其他2组(F=9.576 0、7.139 0, 均P < 0.05), Prevotellaceae和Helicobacteraceae在ND组显著高于其他2组(F=130.123 0、20.321 0, 均P < 0.05);(4)KEGG功能预测发现不同饲喂方式小鼠空肠微生物的功能主要在碳水化合物代谢、复制和修复等方面富集; 通过PPIs聚类发现空肠微生物主要富集在碳水化合物代谢、能量吸收等方面。

高脂饲喂使小鼠肠道菌群结构发生变化, 有益菌数量减少, 进而损伤肠道上皮组织, 破坏肠道屏障, 使其功能发生紊乱。

     

Inhibition of biofouling by marine microorganisms and their metabolites

Development of microbial biofilms and the recruitment of propagules on the surfaces of man-made structures in the marine environment cause serious problems for the navies and for marine industries around the world. Current antifouling technology is based on the application of toxic substances that can be harmful to the natural environment. For this reason and the global ban of tributyl tin (TBT), there is a need for the development of "environmentally-friendly" antifoulants. Marine microbes are promising potential sources of non-toxic or less-toxic antifouling compounds as they can produce substances that inhibit not only the attachment and/or growth of microorganisms but also the settlement of invertebrate larvae and macroalgal spores. However, so far only few antilarval settlement compounds have been isolated and identified from bacteria. In this review knowledge about antifouling compounds produced by marine bacteria and diatoms are summarised and evaluated and future research directions are highlighted.