Mutations in DNMT1 cause hereditary sensory neuropathy with dementia and hearing loss

DNA methyltransferase 1 (DNMT1) is crucial for maintenance of methylation, gene regulation and chromatin stability. DNA mismatch repair, cell cycle regulation in post-mitotic neurons and neurogenesis are influenced by DNA methylation. Here we show that mutations in DNMT1 cause both central and peripheral neurodegeneration in one form of hereditary sensory and autonomic neuropathy with dementia and hearing loss. Exome sequencing led to the identification of DNMT1 mutation c.1484A>G (p.Tyr495Cys) in two American kindreds and one Japanese kindred and a triple nucleotide change, c.1470-1472TCC>ATA (p.Asp490Glu-Pro491Tyr), in one European kindred. All mutations are within the targeting-sequence domain of DNMT1. These mutations cause premature degradation of mutant proteins, reduced methyltransferase activity and impaired heterochromatin binding during the G2 cell cycle phase leading to global hypomethylation and site-specific hypermethylation. Our study shows that DNMT1 mutations cause the aberrant methylation implicated in complex pathogenesis. The discovered DNMT1 mutations provide a new framework for the study of neurodegenerative diseases.     

富营养化水体中的溶源性浮游细菌分布与环境因子的关系

使用非侵害性根吸收硝酸盐检测系统,在较低NO3-浓度下,测定10 m mol/L的蔗糖、葡萄糖、果糖、半乳糖、棉子糖、D-甘露醇、甘露糖、阿拉伯糖、乳糖对水稻品种"汕优63"硝酸盐吸收的影响,以10 min为间隔连续测定4 h,结果表明:加入蔗糖后对水稻硝酸盐的吸收有显著的、立即的、持续的促进作用,与加入蔗糖前相比,硝酸盐净吸收率上升了298%,葡萄糖、半乳糖、果糖、棉子糖对水稻硝酸盐的吸收亦有明显的促进作用,上升幅度140%～223%;乳糖、D-甘露醇、阿拉伯糖无明显影响;甘露糖则有抑制作用.蔗糖可能足作为主要的信号分子参与植物硝酸盐吸收的正反馈调控.