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．     

烷化剂NTG诱变虾青素产生菌红法夫酵母的研究

虾青素是一种很有效的生物抗氧化剂和某些生物的天然着色剂,应用前景广阔。红法夫酵母是 生产虾青素的一个来源,优点颇多。天然菌株虾青素产量较少,缺少实用价值。实验采用烷化剂ＮＴＧ 诱变红法夫酵母,筛选出类胡萝卜素产量高的诱变株。用薄层层析对红法夫酵母产生的色素及其皂 化产物进行分析,并对各个成分的扫描光谱进行了比较。认为红法夫酵母产生的类胡萝卜素成分主 要是虾青素及虾青素二酯,还有一部分β－胡萝卜素。同时,还对虾青素产生的时相和ＢＨＴ对虾青素 光分解的保护作用进行了初步研究。     

松嫩平原羊草草地土壤-植物间铁的动态研究

羊草草地土壤-植物间营养元素Fe的动态研究结果表明,土壤中全铁和有效铁含量均较低,羊草中Fe含量比较丰富．在生长季各时期,全铁和有效铁含量在土壤剖面分布上从上向下呈下降趋势,有效铁与有机质含量呈显著正相关,而与pH值呈显著负相关．全铁各月平均含量变化在生长季呈“V”型曲线,7月含量最低;有效铁平均含量从5～8月与全铁相似,8月后则逐渐减少．羊草各器官及枯落物Fe含量有很大变化,总的趋势是根>根茎>叶>枯落物>茎;羊草叶、茎的Fe含量在生长季中为波动型下降曲线,根茎、根及枯落物的Fe含量在生长季中为“V”型曲线．A层土壤富集有效铁的能力稍强．土壤中Fe活性平均为0．640％。从5月至8月逐渐升高,8月后逐渐下降,10月份最低．地下部的Fe向地上部的转移强度为5～7月下降,8月升高,随后又下降．地上部Fe向枯落物的转移强度平均为105．0％,与地下部Fe向地上部转移强度呈显著负相关。     

治疗耐甲氧西林金黄色葡萄球菌感染的抗体药物

耐甲氧西林金黄色葡萄球菌(methicillin-resistant staphylococcus aureus, MRSA) 作为超级细菌的典型代表,严重威胁人民群众的健康。目前经典的抗生素治疗和疫苗主动预防都无法有效控制MRSA的感染。近年来,随着抗体药物产业的兴起,诸多药物研发公司和研究人员致力于研究治疗性抗体,以期控制MRSA的感染并已经取得了很多突破。就治疗MRSA感染的抗体药物研究进展作一简要综述。     

Association between polymorphisms in the promoter region of interleukin-10 and susceptibility to inflammatory bowel disease

The aim of this study was to assess the association of polymorphisms in the promoter region of the IL-10 gene with the risk of inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC). Fifteen studies (3,693 cases and 4,574 controls) were included in a meta-analysis of association between IL-10 ?1082G/A, ?819C/T and ?592C/A polymorphisms, and IBD, CD and UC using allele contrast and the recessive, dominant, and additive models. Hardy–Weinberg equilibrium was confirmed for each study. Heterogeneity and study quality were investigated using stratification analyses and sensitivity analyses. Polymorphism ?1082G/A showed significant association with CD, with odds ratios (ORs) for the GG + GA genotype and GG versus AA genotype of 1.278 (1.004–1.627) and 1.238 (1.027–1.492) in all subjects. Significant associations were found in the Caucasian subgroup using the allele contrast, dominant, and additive models. C-allele carriers of the ?819C/T polymorphism were at increased risk of IBD (OR 1.093, 95 % CI 1.004–1.190). Association with the ?819C/T polymorphism was also found in Caucasians with CD (C vs. T: OR 1.104, 95 % CI 1.010–1.206; CC + CT vs. TT: OR 1.328, 95 % CI 1.006–1.754; CC vs. TT: OR 1.339, 95 % CI 1.008–1.778), and with UC (CC vs. CT + TT: OR 1.188, 95 % CI 1.019–1.385). No significant association was found between the ?592C/A polymorphism and IBD, CD or UC. In conclusion, the meta-analysis demonstrated clear association between the IL-10 polymorphisms ?1082G/A and ?819C/T and the risk of IBD.     

禽病原性大肠杆菌1型菌毛的分离与鉴定

以旋涡混合法使禽病原性大肠杆菌分离株566、1794和TK3菌毛脱落,经硫酸铵沉淀、透析后进行蔗糖密度梯度离心,收集密度为110至115g/cm3的蛋白带,经SDSPAGE测定,3株菌菌毛蛋白的分子量分别在175、170和170kD;提纯菌毛保留了甘露糖敏感性凝集豚鼠红细胞的能力,证明它们为1型菌毛;从1794株提取的1型菌毛免疫BALB/C小鼠产生的高免血清在Western blot中与3个菌株的相应菌毛蛋白均呈阳性反应。上述结果表明,受检的3株禽病原性大肠杆菌均表达了1型菌毛,其分子量在175～170kD之间,3个菌株的1型菌毛间具有较强的抗原相关性。