Selective pericentromeric heterochromatin dismantling caused by TP53 activation during senescence

Cellular senescence triggers various types of heterochromatin remodeling that contribute to aging. However, the age-related mechanisms that lead to these epigenetic alterations remain elusive. Here, we asked how two key aging hallmarks, telomere shortening and constitutive heterochromatin loss, are mechanistically connected during senescence. We show that, at the onset of senescence, pericentromeric heterochromatin is specifically dismantled consisting of chromatin decondensation, accumulation of DNA breakages, illegitimate recombination and loss of DNA. This process is caused by telomere shortening or genotoxic stress by a sequence of events starting from TP53-dependent downregulation of the telomere protective protein TRF2. The resulting loss of TRF2 at pericentromeres triggers DNA breaks activating ATM, which in turn leads to heterochromatin decondensation by releasing KAP1 and Lamin B1, recombination and satellite DNA excision found in the cytosol associated with cGAS. This TP53–TRF2 axis activates the interferon response and the formation of chromosome rearrangements when the cells escape the senescent growth arrest. Overall, these results reveal the role of TP53 as pericentromeric disassembler and define the basic principles of how a TP53-dependent senescence inducer hierarchically leads to selective pericentromeric dismantling through the downregulation of TRF2.     

发酵液内氨甲酰妥布拉霉素的定量测定

报道了应用一种以测量图象面积为指标的Ｚｙ－３００Ａ多功能抑菌圈测量仪,能够精确、稳定、快速地测定发酵液经薄层层析生物显迹后单组分氨甲酰妥布拉霉素的抑菌斑面积,然后从绘制的标准曲线中直接读取氨甲酸妥布拉霉素在发酵液中的含量,从而排除了其他组分对测定的干扰。试验证明,用Ｚｙ－３００Ａ多功能抑菌圈测量仪测定抗生素薄层层析生物显迹的抑菌斑,具有线性宽、精密度高、重复性强、操作简单方便等优点．本方法的建立为抗生素的纯品检定和多组分抗生素发酵、分离和纯化提供了准确的定量数据．     

凤尾蕨内生真菌的研究Ⅱ——1株产芦丁内生真菌初步研究

报道了从凤尾蕨属井栏边草(Pteris multifida)根状茎中分离出一内生真菌——菌株JJF006,对其形态特征进行了初步研究,并用TLC对该菌株培养物进行了分析。初步结果表明:该真菌液体培养基中含有芦丁成分。     

大兴安岭地区粘细菌资源的多样性及其生物活性

【背景】粘细菌是一类具有社会性行为的高等原核生物,其代谢产物具有丰富、多样、新颖的生物活性,是筛选天然药物的良好资源,具有很大的研究开发应用价值。【目的】分析大兴安岭地区粘细菌资源的多样性;分离纯化可培养的粘细菌,分析其抗菌活性并从中筛选对马铃薯晚疫病菌具有拮抗作用的菌株。【方法】通过变性梯度凝胶电泳(DGGE)技术对从大兴安岭地区采集的15个土样中粘细菌资源的多样性进行分析,利用兔粪诱导、大肠杆菌划线诱导和滤纸诱导3种方法从土样中分离可培养的粘细菌,结合形态观察、生理生化特征和16S rRNA基因序列分析确定这些菌株的分类地位,通过平板对峙法对其进行抗菌活性分析。【结果】DGGE的分析结果显示,15个土样中共鉴定到13个属的粘细菌,基本覆盖了大部分已知的粘细菌种属以及部分未分类的粘细菌,表现出了丰富的多样性。共分离得到88株菌,从中得到22株纯菌,经鉴定属于2个属(粘球菌属与珊瑚球菌属)8个种(黄色粘球菌、橙色粘球菌、变绿粘球菌、珊瑚粘球菌、具枝粘球菌、大孢珊瑚球菌、弱小珊瑚球菌和珊瑚状珊瑚球菌)。抗菌结果显示:22株纯菌均表现出可以对一种甚至多种指示菌产生抗性,其中19株抑制大肠杆菌的生长,14株抑制马铃薯晚疫病菌的生长,8株抑制金黄色葡萄球菌的生长,13株抑制酿酒酵母菌的生长,7株抑制枯草芽孢杆菌的生长。【结论】内蒙古大兴安岭地区蕴藏着丰富的粘细菌资源,粘球菌属及珊瑚球菌属可能为该地区粘细菌菌群中的优势菌。分离纯化出的粘细菌菌株均表现出抑制一种甚至多种指示菌生长的活性,其中64%的纯菌对马铃薯晚疫病菌产生抗性,具有进一步研究的潜在价值。     

Reconstruction of Surface Porous PEEK Decorated with Strontium-doped Calcium Phosphate Coatings for Enhancing Osteogenic Activity

The aim of this study was to reconstruct surface porous structure with hundreds of micrometers and then bio-mineralize Sr-doped Calcium Phosphate(Sr-doped CaP)o...     

Design,synthesis and biological evaluation of novel diosgenin–benzoic acid mustard hybrids with potential anti-proliferative activities in human hepatoma HepG2 cells

To discover new lead compounds with anti-tumour activities, in the present study, natural diosgenin was hybridised with the reported benzoic acid mustard pharmacophore. The in vitro cytotoxicity of the resulting newly synthesised hybrids (8–10, 14a–14f, and 15a–15f) was then evaluated in three tumour cells (HepG2, MCF-7, and HeLa) as well as normal GES-1 cells. Among them, 14f possessed the most potential anti-proliferative activity against HepG2 cells, with an IC₅₀ value of 2.26 µM, which was 14.4-fold higher than that of diosgenin (IC₅₀ = 32.63 µM). Furthermore, it showed weak cytotoxicity against GES-1 cells (IC₅₀ > 100 µM), thus exhibiting good antiproliferative selectivity between normal and tumour cells. Moreover, 14f could induce G0/G1 arrest and apoptosis of HepG2 cells. From a mechanistic perspective, 14f regulated cell cycle-related proteins (CDK2, CDK4, CDK6, cyclin D1 and cyclin E1) as well mitochondrial apoptosis pathway-related proteins (Bax, Bcl-2, caspase 9, and caspase 3). These findings suggested that hybrid 14f serves as a promising anti-hepatoma lead compound that deserves further research.     

Alternatively activated macrophages at the recipient site improve fat graft retention by promoting angiogenesis and adipogenesis

The inflammatory response mediated by macrophages plays a role in tissue repair. Macrophages preferentially infiltrate the donor site and subsequently, infiltrate the recipient site after fat grafting. This study aimed to trace host‐derived macrophages and to evaluate the effects of macrophage infiltration at the recipient site during the early stage on long‐term fat graft retention. In our novel mouse model, all mice underwent simulated liposuction and were divided into 2 groups. The fat procurement plus grafting (Pro‐Grafting) group was engrafted with prepared fat (0.3 ml). The pro‐Grafting+M2 group was engrafted with prepared fat (0.3 ml) mixed with 1.0 × 10⁶ GFP+M0 macrophages, and then, 2 ng IL‐4 was injected into the grafts on Day 3. In addition, 1.0 × 10⁶ GFP+M0 macrophages were injected into the tail vein for tracing in the Pro‐Grafting group. As a result, GFP+macrophages first infiltrated the donor site and subsequently infiltrated the recipient site in the Pro‐Grafting group. The long‐term retention rate was higher in the Pro‐Grafting+M2 group (52% ± 6.5%) than in the Pro‐Grafting group (40% ± 3.5%). CD34+ and CD31+ areas were observed earlier, and expression of the adipogenic proteins PPAR‐γ, C/EBP and AP2 was higher in the Pro‐Grafting+M2 group than in the Pro‐Grafting group. The host macrophages preferentially infiltrate the donor site, and then, infiltrate the recipient site after fat grafting. At the early stage, an increase in macrophages at the recipient site may promote vascularization and regeneration, and thereby improve the fat graft retention rate.     

典型亚热带热分层水库秋季细菌群落垂直分布

水库在我国东南沿海地区是重要的饮用水水源地,对地区经济发展和社会稳定起到重要作用。选择亚热带地区典型的热分层水库——福建莆田东圳水库,于2011年秋季稳定分层期,以水体温度的垂直变化特征为依据进行分层采样。应用PCRDGGE和克隆测序的方法研究浮游细菌群落的垂直分布特征,利用多元统计分析揭示细菌群落与热分层水体理化指标之间的关系。结果显示:溶解氧、电导率、叶绿素a、总氮、氨氮及硝氮在上下层水体中的分布有显著差异,下层缺氧区细菌的ShannonWiener指数和DGGE条带数明显高于上层好氧区,表明东圳水库热分层水体中存在明显的物理、化学及生物分层现象。测序结果表明β-变形菌可能是东圳水库中占优势的细菌类群,统计结果提示溶解氧是显著影响细菌群落组成的环境因子。热分层水体的物理化学分层与水体细菌群落结构密切相关,提示水库生态学研究应对水体热分层给予重视。     

Electron acceptors for anaerobic oxidation of methane drive microbial community structure and diversity in mud volcanoes

Mud volcanoes (MVs) emit globally significant quantities of methane into the atmosphere, however, methane cycling in such environments is not yet fully understood, as the roles of microbes and their associated biogeochemical processes have been largely overlooked. Here, we used data from high‐throughput sequencing of microbial 16S rRNA gene amplicons from six MVs in the Junggar Basin in northwest China to quantify patterns of diversity and characterize the community structure of archaea and bacteria. We found anaerobic methanotrophs and diverse sulfate‐ and iron‐reducing microbes in all of the samples, and the diversity of both archaeal and bacterial communities was strongly linked to the concentrations of sulfate, iron and nitrate, which could act as electron acceptors in anaerobic oxidation of methane (AOM). The impacts of sulfate/iron/nitrate on AOM in the MVs were verified by microcosm experiments. Further, two representative MVs were selected to explore the microbial interactions based on phylogenetic molecular ecological networks. The sites showed distinct network structures, key species and microbial interactions, with more complex and numerous linkages between methane‐cycling microbes and their partners being observed in the iron/sulfate‐rich MV. These findings suggest that electron acceptors are important factors driving the structure of microbial communities in these methane‐rich environments.