热量限制通过HNF3γ下调NOX4表达来抑制内皮细胞的衰老

为了观察热量限制对主动脉内皮细胞中HNF3γ及NOX4基因表达的影响, 揭示HNF3γ-NOX4-活性氧通路介导热量限制抗内皮细胞衰老的分子机制, 文章将主动脉内皮细胞分为5组：对照组、高热量组、低热量组、siRNA+低热量组、siRNA+高热量组。应用逆转录实时定量PCR(Real-time quantitative PCR, RT-qPCR)、Western blotting分析各组HNF3γ、NOX4 mRNA及蛋白水平变化, 并检测各组细胞内活性氧产量及细胞衰老程度变化。采用染色质免疫共沉淀分析HNF3γ蛋白与NOX4基因启动子区域结合情况, 萤光素酶报告基因检测HNF3γ蛋白结合后对NOX4基因启动子活性的影响。结果显示：与对照组比较, 低热量组HNF3γ mRNA和总HNF3γ蛋白表达水平、磷酸化/总HNF3γ比值显著升高(P<0.05), NOX4 mRNA和蛋白表达水平、细胞内活性氧产量及细胞衰老程度显著降低(P<0.05); 高热量组HNF3γ mRNA和总HNF3γ蛋白表达水平、磷酸化/总HNF3γ比值显著降低(P<0.05), NOX4 mRNA和蛋白表达水平、细胞内活性氧产量及细胞衰老程度显著升高(P<0.05); siRNA+低热量组及siRNA+高热量组中NOX4 mRNA和蛋白表达水平、细胞内活性氧水平及细胞衰老程度显著升高(P< 0.05)。染色质免疫共沉淀证实HNF3γ蛋白可与NOX4基因启动区域4个结合位点(-6 bp、-76 bp、-249 bp、-954 bp)结合。萤光素酶报告基因检测显示HNF3γ蛋白与NOX4启动子区域1个位点(-6 bp)、2个位点(-6、-76 bp)、3个位点(-6、-76、-249 bp)、4个位点(-6、-76、-249、-954 bp)结合, 可使NOX4启动子活性分别降低至对照组的80.15±4.64%、40.02.±2.15%、16.46±2.24%、12.13±1.46%, P<0.05。上述结果提示热量限制可上调HNF3γ基因表达, 增强HNF3γ蛋白活性, 促进HNF3γ蛋白同NOX4基因启动子区域结合, 抑制NOX4基因表达, 进而减少细胞内活性氧产生而延缓动脉内皮细胞衰老。     

Effects of acidic pH on predation rates and survivorship of damselfly nymphs

Environmental variables such as pH critically affect the physiology and ecology of aquatic organisms. Our lack of information regarding indirect effects of acid precipitation requires investigation of acid stress and response to acid stress by species of freshwater communities. Damselfly nymphs Enallagma civile (Odonata: Coenagrionidae) are abundant aquatic predators and food items for other secondary consumers.We investigated the effects of low pH on mortality, survivorship, predation rate, respiration rate, and caloric content of nymphs of E. civile. We hypothesized that acid stress would increase mortality and decrease predation rate among surviving individuals. We hypothesized that respiration rate and caloric content as measures of physiological condition would decrease in acid-stress conditions.We cultured individual early-instar nymphs in the laboratory with a controlled diet of mosquito larvae. The nymphs were reared to final instar in pond water and artificially reconstituted soft water (RSW) adjusted to pH 3.5, 4.5, 5.5, and ambient conditions of the collection site.Predation rate was significantly lower in RSW than in pond water in treatments of equivalent H⁺ concentrations. This indicated stress from differences in dissolved solids in RSW compared with pond water. Acid conditions significantly affected predation rates in pond water, but only at pH 3.5 and only for the largest instar. Mortality increased and survivorship decreased at low pH. Early-instar mortality and survivorship were particularly susceptible to acid stress. Treatments of pH 4.5, 5.5 and ambient did not significantly alter respiration rate or caloric content. However, respiration rate and caloric content increased at pH 3.5.Damselfly nymphs tolerated pHs as low as 4.5 without significant changes (including predation rate). However, the effects of pH 3.5 were significant and greatly lowered the predation and fitness of the nymphs.author for correspondence     

Caloric restriction augments radiation efficacy in breast cancer

Dietary modification such as caloric restriction (CR) has been shown to decrease tumor initiation and progression. We sought to determine if nutrient restriction could be used as a novel therapeutic intervention to enhance cytotoxic therapies such as radiation (IR) and alter the molecular profile of triple-negative breast cancer (TNBC), which displays a poor prognosis. In two murine models of TNBC, significant tumor regression is noted with IR or diet modification, and a greater regression is observed combining diet modification with IR. Two methods of diet modification were compared, and it was found that a daily 30% reduction in total calories provided more significant tumor regression than alternate day feeding. At the molecular level, tumors treated with CR and IR showed less proliferation and more apoptosis. cDNA array analysis demonstrated the IGF-1R pathway plays a key role in achieving this physiologic response, and multiple members of the IGF-1R pathway including IGF-1R, IRS, PIK3ca and mTOR were found to be downregulated. The innovative use of CR as a novel therapeutic option has the potential to change the biology of tumors and enhance the opportunity for clinical benefit in the treatment of patients with TNBC.     

Caloric restriction impacts plasma microRNAs in rhesus monkeys

Caloric restriction (CR) is one of the most robust interventions shown to delay aging in diverse species, including rhesus monkeys (Macaca mulatta). Identification of factors involved in CR brings a promise of translatability to human health and aging. Here, we show that CR induced a profound change in abundance of circulating microRNAs (miRNAs) linked to growth and insulin signaling pathway, suggesting that miRNAs are involved in CR's mechanisms of action in primates. Deep sequencing of plasma RNA extracts enriched for short species revealed a total of 243 unique species of miRNAs including 47 novel species. Approximately 70% of the plasma miRNAs detected were conserved between rhesus monkeys and humans. CR induced or repressed 24 known and 10 novel miRNA species. Regression analysis revealed correlations between bodyweight, adiposity, and insulin sensitivity for 10 of the CR‐regulated known miRNAs. Sequence alignment and target identification for these 10 miRNAs identify a role in signaling downstream of the insulin receptor. The highly abundant miR‐125a‐5p correlated positively with adiposity and negatively with insulin sensitivity and was negatively regulated by CR. Putative target pathways of CR‐associated miRNAs were highly enriched for growth and insulin signaling that have previously been implicated in delayed aging. Clustering analysis further pointed to CR‐induced miRNA regulation of ribosomal, mitochondrial, and spliceosomal pathways. These data are consistent with a model where CR recruits miRNA‐based homeostatic mechanisms to coordinate a program of delayed aging.     

互花米草人工植被生态效益和经济效益的初步研究

前言在我国海涂中被日潮淹没的中、低潮带,天然生长的高等植物种类比较贫乏,分布面积也较小,许多中低潮带海滩为光滩裸地。为了绿化海滩、保护海滩,提高海滩生态系统的初级生产力,我国在1963年和1978年分别从英国     

火烧及微地貌对高原湿草甸优势种华扁穗草地上部灰分含量及热值的影响

为探讨火烧干扰以及微地貌差异对高原湿草甸植被的影响,以高原湿草甸优势种华扁穗草( Blysmus sinocompressus Tang et F. T. Wang)为研究对象,分别在经历火烧干扰和未烧的湿地中选择平地和地垄作为样地,研究了不同生长期以及不同年份华扁穗草地上部的灰分含量和热值(包括干质量热值和去灰分热值)变化。结果表明：在火烧平地、火烧地垄、未烧平地和未烧地垄4类样地中,不同生长期以及不同年份间华扁穗草地上部的灰分含量和热值均有一定差异。在火烧平地、火烧地垄和未烧平地3类样地中,与生长初期相比,生长旺盛期华扁穗草地上部的灰分含量均降低,其干质量热值和去灰分热值均升高;而在未烧地垄样地中,与生长初期相比,生长旺盛期华扁穗草地上部的灰分含量显著升高,其干质量热值和去灰分热值则均略降低。从样地类型看,在生长旺盛期,平地样地中华扁穗草地上部的灰分含量均低于地垄样地,其干质量热值和去灰分热值均高于地垄样地,其中,其灰分含量在火烧平地样地中最低、在未烧地垄样地中最高;其干质量热值和去灰分热值在火烧地垄样地中均最低、在未烧平地样地中均最高,但总体无显著差异。随时间推移,火烧样地特别是火烧平地样地中华扁穗草地上部的灰分含量增加,而其干质量热值和去灰分热值则有所降低但总体上与未烧样地间无显著差异。总体上看,在火烧样地中,华扁穗草地上部的干质量热值和去灰分热值低于未烧样地;而在平地样地中,其干质量热值和去灰分热值高于地垄样地。研究结果显示：火烧干扰和微地貌差异对华扁穗草地上部的灰分含量和热值均有一定的影响,据此,建议将植物地上部的灰分含量和热值作为高原湿草甸植被优势种响应环境扰动的参考指标。     

盐度对秋茄凋落叶分解过程中物质与能量动态的影响

在室内人工模拟潮汐, 研究了4种盐度(0、10‰、25‰和35‰, 分别代表淡水、低盐、中盐和高盐)下秋茄(Kandelia candel)凋落叶分解过程中物质与能量动态的差异。结果表明, 高盐处理下的失重率和平均分解速率显著低于淡水和低盐处理, 而高盐下的半分解理论值则高于其他处理; 盐度对分解过程中的残叶氮磷变化动态有显著影响, 其中, 残叶氮的释放速率在实验后期会随着盐度的升高而上升, 高盐度下残叶总氮含量显著低于低盐或淡水处理; 而在分解第1周, 淡水或低盐处理能加速磷的释放, 但中高盐度残叶中总磷含量最终会低于淡水和低盐处理; 盐度同样能对残叶热值产生显著影响, 淡水和低盐处理下的碎屑热值要显著高于高盐处理下的残叶热值, 但不同盐度下分解的能量损失差异不显著。     

DNA replication stress-induced loss of reproductive capacity in S. cerevisiae and its inhibition by caloric restriction

In many organisms, attenuation of growth signaling by caloric restriction or mutational inactivation of growth signaling pathways extends lifespan and protects against cancer and other age-related diseases. The focus of many efforts to understand these effects has been on the induction of oxidative stress defenses that inhibit cellular senescence and cell death. Here we show that in the model organism S. cerevisiae, growth signaling induces entry of cells in stationary phase into S phase in parallel with loss of reproductive capacity, which is enhanced by elevated concentrations of glucose. Overexpression of RNR1 encoding a ribonucleotide reductase subunit required for the synthesis of deoxynucleotide triphosphates and DNA replication suppresses the accelerated loss of reproductive capacity of cells cultured in high glucose. The reduced reproductive capacity of these cells is also suppressed by excess threonine, which buffers dNTP pools when ribonucleotide reductase activity is limiting. Caloric restriction or inactivation of the AKT homolog Sch9p inhibits senescence and death in stationary phase cells caused by the DNA replication inhibitor hydroxyurea or by inactivation of the DNA replication and repair proteins Sgs1p or Rad27p. Inhibition of DNA replication stress represents a novel mechanism by which caloric restriction promotes longevity in S. cerevisiae. A similar mechanism may promote longevity and inhibit cancer and other age-related diseases in humans.     

罗汉果甜苷V的合成生物学研究进展

罗汉果甜苷V是罗汉果甜苷中含量和甜度均较高的成分,具有止咳祛痰、抗癌、抗氧化、调节血糖等诸多药理活性,成为兼具治疗功能的天然非糖甜味剂,具有广阔的市场前景。然而目前有限的生物资源和较高的提取成本,限制了它的广泛应用。合成生物学的快速发展为植物天然产物的生产提供了一种新思路,通过构建罗汉果甜苷V的微生物细胞工厂,将实现其低成本、规模化生产。文中介绍了罗汉果甜苷V的结构及药理活性,重点综述了罗汉果甜苷V的合成生物学研究进展,并探讨了当前研究所面临的挑战,以期为罗汉果甜苷V生物合成的进一步研究提供参考。