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Conantokin-T (con-T) and conantokin-G (con-G) are two highly homologous peptide toxins found in Conus venom. The former is a 21-residue peptide with four gamma-carboxyglutamic acid (Gla) residues (at positions 3, 4, 10 and 14), while the latter is a 17-residue peptide with five gamma-carboxyglutamic acid residues (at positions 3, 4, 7, 10 and 14). Despite the apparent similarity in number and relative positions of the gamma-carboxyglutamic acid residues, (113)Cd-NMR studies indicated a distinct metal binding behavior for con-G and con-T. There appears to be four binding sites in con-G in contrast to one metal binding site in con-T. To elucidate the mode of calcium binding by the gamma-carboxyglutamic acid residues in these conantokins, we designed various analogous peptides with their gamma-carboxyglutamic acid replaced by other amino acid residues. (113)Cd-NMR experiments on conantokin analogues reveal that the major difference in the number of metal binding sites between con-G and con-T is due to the residue at position 7. We also performed molecular simulations to calculate the relative binding free energies of several potential binding sites. Based on our theoretical and experimental results, we propose a 'four-site' binding model for conantokin-G and a 'single-site' binding model for conantokin-T.  相似文献   
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Epigenetic dysregulation plays a crucial role in cardiovascular diseases. Previously, we reported that acetyltransferase p300 (ATp300) inhibitor L002 prevents hypertension‐induced cardiac hypertrophy and fibrosis in a murine model. In this short communication, we show that treatment of hypertensive mice with ATp300‐specific small molecule inhibitor L002 or C646 reverses hypertension‐induced left ventricular hypertrophy, cardiac fibrosis and diastolic dysfunction, without reducing elevated blood pressures. Biochemically, treatment with L002 and C646 also reverse hypertension‐induced histone acetylation and myofibroblast differentiation in murine ventricles. Our results confirm and extend the role of ATp300, a major epigenetic regulator, in the pathobiology of cardiac hypertrophy and fibrosis. Most importantly, we identify the efficacies of ATp300 inhibitors C646 and L002 in reversing hypertension‐induced cardiac hypertrophy and fibrosis, and discover new anti‐hypertrophic and anti‐fibrotic candidates.  相似文献   
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Wang  Ran  Xie  Lyu  Gao  Na  Fan  Dongying  Chen  Hui  Wang  Peigang  Zhou  Hongning  An  Jing 《中国病毒学》2019,34(3):243-252
The incidence of Japanese encephalitis(JE) has significantly decreased in China due to JE vaccines. In this study, we investigated the post-JE vaccination seroprevalence and protection provided by vaccinated sera against Japanese encephalitis virus(JEV) to elucidate the persistence and waning of antibodies to JEV among JE-SA14-14-2-vaccinated children. A total of 300 serum samples were collected from vaccinated children aged 3–10 years in Zhaotong, Yunnan,China. The seroprevalence of anti-JEV antibodies was determined by enzyme-linked immune sorbent assay and plaque reduction neutralization test. The highest seropositivity of 82% was observed in vaccinated children during the first0.5–1.5 years after booster vaccination. Then, the seropositivity began to decline and remained lower than the original level observed in the 0.5–1.5-year group. An association was found between the waning of seroprevalence and elapsed time of the post-booster vaccination. Similarly, the neutralizing antibody(nAb) titres gradually decreased over time, and the levels showed a positive correlation with the protective efficacy in mice. This finding suggests that nAbs play an important role in the antiviral process and that the nAb titre is an adequately credible parameter for evaluating the protective efficacy induced by the JE vaccine. Our results provide data that clarify the persistence and waning of antibodies to JEV, which may help elucidate the pathogenesis of JE.  相似文献   
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Plants are considered an important food and nutrition source for humans. Despite advances in plant seed metabolomics, knowledge about the genetic and molecular bases of rice seed metabolomes at different developmental stages is still limited. Here, using Zhenshan 97 (ZS97) and Minghui 63 (MH63), we performed a widely targeted metabolic profiling in seeds during grain filling, mature seeds and germinating seeds. The diversity between MH63 and ZS97 was characterized in terms of the content of metabolites and the metabolic shifting across developmental stages. Taking advantage of the ultra‐high‐density genetic map of a population of 210 recombinant inbred lines (RILs) derived from a cross between ZS97 and MH63, we identified 4681 putative metabolic quantitative trait loci (mQTLs) in seeds across the three stages. Further analysis of the mQTLs for the codetected metabolites across the three stages revealed that the genetic regulation of metabolite accumulation was closely related to developmental stage. Using in silico analyses, we characterized 35 candidate genes responsible for 30 structurally identified or annotated compounds, among which LOC_Os07g04970 and LOC_Os06g03990 were identified to be responsible for feruloylserotonin and l ‐asparagine content variation across populations, respectively. Metabolite?agronomic trait association and colocation between mQTLs and phenotypic quantitative trait loci (pQTLs) revealed the complexity of the metabolite?agronomic trait relationship and the corresponding genetic basis.  相似文献   
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Morphogenesis of the soil hypotrich ciliate, Holostichides chardezi Foissner, 1987, collected from southeastern China, was investigated using the protargol staining method. The main morphogenetic events follow a similar process with that of its congeners. Phylogenetic analyses based on the SSU rDNA sequence data indicate that Holostichides is nonmonophyletic; H. chardezi, the type species of Holostichides, clusters with H. heterotypicus, while H. terrae is distinctly separate from these species. H. terrae can be distinguished from H. chardezi (type species of Holostichides) and H. heterotypicus by undulating membranes relatively long and distinctly curved (vs. relatively short and straight), pharynx with (vs. without) rod‐shaped structure, and two (vs. more than two) frontoterminal cirri. Therefore, a new genus, Anteholostichides nov. gen., has been proposed for H. terrae. Further, the diagnosis of the genus Holostichides is improved.  相似文献   
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恢复梯度上华中亚热带森林生物多样性、林分因子及功能特性对生物量、生产力的影响 草地群落上进行的控制实验大都发现生物多样性对生态系统功能有显著促进作用。然而,在天然林中,多样性与林分因子、群落功能特性的相对作用大小仍存在争议。本文在森林恢复梯度上,研究这3类因素对生物量和生产力的相对影响。我们在湖北神农架设置了处于不同恢复阶段的24块(600 m2)亚热 带森林样地,计算了林分生物量和生产力。选择5个关键的植物功能性状,并计算了群落的功能多样性(功能丰富度、功能均匀度和功能离散度)和性状的加权平均值(CWM)。使用一般线性模型(GLMs)、变异分离等方法探究林分因子(密度、林龄、群落最大树高等)、功能特性、物种和功能多样性对生物量和生产力的相对重要性。研究结果表明,随着森林恢复,林分生物量和生产力显著增加,群落物种丰富度显著增加,而功能离散度显著降低。变异分离结果表明,多样性对生物量和生产力的单独效应不显著,但可能通过与林分因子和功能特性的协同效应来影响生物量和生产力。总体而言,我们发现林分因子对亚热带森林生物量和生产力的影响最大,功能特性显著影响生产力,但不影响生物量。这些结果说明,在森林经营中,调整林分结构和群落物种特性是提高森林碳储量和固碳潜力的有效途径。  相似文献   
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