The mucosal adjuvanticity of the oligodeoxynucleotides containing a non-methylated CpG motif on BCG and diphtheria toxoid

CpG-DNA is currently attracting attention as an effective and safe vaccine adjuvant to prevent from microbial infections. In this report, we examined the effects of oligo B, which is a synthetic CpG-DNA, in mucosal administration of Bacillus Calmette-Guérin (BCG) and diphtheria toxoid (DT). Co-administration with oligo B enhanced BCG-induced delayed type hypersensitivity to purified protein derivative (PPD) in guinea pigs. The titers of anti-DT serum IgG, IgA and mucosal IgA antibodies induced by intranasal administration with DT plus oligo B were significantly higher than that with DT alone. In both C57BL/6 and BALB/c mice, intranasal administration of DT with oligo B induced enough level of antibodies to prevent onset of diphtheria. The analysis of antibody subclasses showed that intranasal administration of oligo B induced not only IgG1 but also IgG2a, IgG2c and IgA anti-DT antibodies. In contrast, there was no or little production of the anti-DT serum IgE. Taken together our data suggest that oligo B is a powerful adjuvant in mucosal immunization.     

A novel vaccine adjuvant comprised of a synthetic innate defence regulator peptide and CpG oligonucleotide links innate and adaptive immunity

There has been an increased demand for the development of novel vaccine adjuvants that lead to enhanced induction of protection from infectious challenges and development of immunological memory. A novel vaccine adjuvant was developed comprising a complex containing CpG oligonucleotide and the synthetic cationic innate defence regulator peptide HH2 that has enhanced immune modulating activities. The complex of HH2 and the CpG oligonucleotide 10101 was a potent inducer of cytokine/chemokine expression ex vivo, retained activity following extended storage, had low associated cytotoxicity, and upregulated surface marker expression in dendritic cells, a critical activity for a vaccine adjuvant. Immunization of mice with a coformulation of the HH2–CpG complex and pertussis toxoid significantly enhanced the induction of toxoid-specific antibody titres when compared to toxoid alone, inducing high titres of IgG1 and IgG2a, typical of a balanced Th1/Th2 response, and also led to high IgA titres.     

NRF2启动子甲基化与男性不育

目的探讨抗氧化基因NRF2启动子上游CpG岛内408⁹94 bp位置处的甲基化水平与男性不育之间的关系。方法酚氯仿法手提精子DNA,建立重亚硫酸盐修饰精子DNA后克隆测序法(即BSP-克隆测序法),选择正常男性及不育中少、弱、畸精症男性患者每份精液样本DNA的抗氧化基因NRF2的三个片段,每个片段选择15994 bp位置处的甲基化水平与男性不育之间的关系。方法酚氯仿法手提精子DNA,建立重亚硫酸盐修饰精子DNA后克隆测序法(即BSP-克隆测序法),选择正常男性及不育中少、弱、畸精症男性患者每份精液样本DNA的抗氧化基因NRF2的三个片段,每个片段选择15²0个正确的克隆结果并比较其甲基化水平。结果不育男性少、弱精组和正常精液组其抗氧化基因NRF2启动子上游40820个正确的克隆结果并比较其甲基化水平。结果不育男性少、弱精组和正常精液组其抗氧化基因NRF2启动子上游408⁹94 bp处99%甲基化位点均为非甲基化状态,正常男性精子DNA第7个甲基化位点缺失率(18.14%)明显比少弱精组(24.9%)缺失率低(P<0.05)。结论虽然正常生育男性及不育男性少、弱精患者抗氧化基因NRF2启动子上游408994 bp处99%甲基化位点均为非甲基化状态,正常男性精子DNA第7个甲基化位点缺失率(18.14%)明显比少弱精组(24.9%)缺失率低(P<0.05)。结论虽然正常生育男性及不育男性少、弱精患者抗氧化基因NRF2启动子上游408⁹94 bp区均呈现非甲基化状态但其第7个甲基化位点缺失可能与精子成熟障碍有关。     

Genomic hypomethylation and CpG island hypermethylation in prostatic intraepithelial neoplasm

Altered DNA methylation in cancer cells is characterized by focal CpG island hypermethylation and diffuse genomic hypomethylation. Both types of aberrant methylation are frequently found in human prostate adenocarcinoma (PCa). Prostatic intraepithelial neoplasm (PIN), a precursor lesion of PCa, has been demonstrated to contain CpG island hypermethylation, but little is known about the role of DNA hypomethylation. We analyzed the methylation status at 12 CpG island loci and at two repetitive DNA elements (LINE-1 and SAT2) from normal prostate (n = 20), PIN (n = 25), and PCa (n = 35) tissues using MethyLight assay or combined bisulfite restriction analysis. The methylation levels in LINE-1 and SAT2 decreased with progression of lesion types from normal prostate to PIN to PCa (P < 0.05), whereas promoter CpG island loci displayed increased methylation. Ten genes were found to be hypermethylated in a cancer-specific manner and were further analyzed in another set of PCa tissues (n = 64). The number of methylated genes was closely associated with TNM stage, Gleason sum, and preoperative serum PSA levels (P = 0.020, 0.073, 0.033, respectively). These results suggest that genomic hypomethylation and CpG island hypermethylation, common among PCas, are early events in prostate carcinogenesis and may be implicated in the development of PIN. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

p53基因甲基化模式的变化及其生物学效应

被誉为基因组保护者的p53是防范哺乳动物基因组损伤的关键抑癌基因之一,其产物在细胞增殖分化过程中发挥着调控细胞周期的作用,参与受损细胞周期抑制、DNA修复、细胞凋亡等维持基因组稳定性相关的各个途径.p53不同位点的甲基化情况与该基因的激活状态、肿瘤的发生等密切相关.该文就p53启动子区域、编码区的CpG位点和编码区非CpG位点的胞嘧啶甲基化改变及其生物学效应作一简要概述.     

From the Cover: An aberrant island-dwelling theropod dinosaur from the Late Cretaceous of Romania

Islands are noted for the occurrence of aberrant, endemic, and dwarfed taxa (the “island effect”). Late Cretaceous vertebrate assemblages of Romania and elsewhere in Europe are classic examples of island faunas in the fossil record, and are characterized by dwarfed herbivorous dinosaurs and other endemic taxa that are noticeably primitive relative to their mainland contemporaries. Fossils of the predators inhabiting the European paleoislands, however, are exceptionally rare and fragmentary. We describe a new dromaeosaurid theropod, based on an articulated skeleton from the Maastrichtian of Romania, which represents the most complete predatory dinosaur from the middle to Late Cretaceous of Europe. This taxon is characterized by a peculiar body plan, most notably extensive fusion in the hand and distal hindlimb, a highly retroverted pelvis with enlarged femoral muscle attachments, and a pair of hyperextensive pedal claws. However, unlike the island-dwelling herbivorous dinosaurs, its closest relatives are contemporary similar-sized Laurasian taxa, indicating faunal connections between Asia and the European islands late into the Cretaceous. This theropod provides support for the aberrant nature of the Late Cretaceous European island-dwelling dinosaurs, but indicates that predators on these islands were not necessarily small, geographically endemic, or primitive.     

Evidence of a conserved functional role for DNA methylation in termites

Many organisms are capable of developing distinct phenotypes from the same genotype. This developmental plasticity is particularly prevalent in insects, which can produce alternate adaptive forms in response to distinct environmental cues. The ability to develop divergent phenotypes from the same genotype often relies on epigenetic information, which affects gene function and is transmitted through cell divisions. One of the most important epigenetic marks, DNA methylation, has been lost in several insect lineages, yet its taxonomic distribution and functional conservation remain uninvestigated in many taxa. In the present study, we demonstrate that the signature of high levels of DNA methylation exists in the expressed genes of two termites, Reticulitermes flavipes and Coptotermes formosanus. Further, we show that DNA methylation is preferentially targeted to genes with ubiquitous expression among morphs. Functional associations of DNA methylation are also similar to those observed in other invertebrate taxa with functional DNA methylation systems. Finally, we demonstrate an association between DNA methylation and the long‐term evolutionary conservation of genes. Overall, our findings strongly suggest DNA methylation is present at particularly high levels in termites and may play similar roles to those found in other insects.     

斜方肌骨肌皮瓣在修复半侧下颌骨切除及口腔软组织缺损中的应用

目的：评价斜方肌骨肌皮瓣修复口腔软组织和半侧下颌骨切除术后缺损的可靠性。方法：10例口腔、颌骨恶性肿瘤患者行半侧下颌骨和累及的软组织手术切除，术后缺损采用斜方肌骨肌皮瓣修复。男6例，女4例，年龄45～79岁，平均年龄61．2岁。T4N0M0期3例，T4N1M0期7例。皮瓣大小为（7cm×6cm）～（16cm×8cm）。结果：8例患者皮瓣全部成活。2例患者皮瓣边缘略有坏死。随访观察7～24个月，7例患者生存良好，无复发；1例患者死于肝、肺转移；2例患者术后复发，行二次手术，目前尚存活。结论：斜方肌骨肌皮瓣是一种修复口腔软组织和下颌骨半侧切除遗留的巨大缺损可靠的方法。