Isocitrate dehydrogenase 1 R132C mutation occurs exclusively in microsatellite stable colorectal cancers with the CpG island methylator phenotype

The CpG Island Methylator Phenotype (CIMP) is fundamental to an important subset of colorectal cancer; however, its cause is unknown. CIMP is associated with microsatellite instability but is also found in BRAF mutant microsatellite stable cancers that are associated with poor prognosis. The isocitrate dehydrogenase 1 (IDH1) gene causes CIMP in glioma due to an activating mutation that produces the 2-hydroxyglutarate oncometabolite. We therefore examined IDH1 alteration as a potential cause of CIMP in colorectal cancer. The IDH1 mutational hotspot was screened in 86 CIMP-positive and 80 CIMP-negative cancers. The entire coding sequence was examined in 81 CIMP-positive colorectal cancers. Forty-seven cancers varying by CIMP-status and IDH1 mutation status were examined using Illumina 450K DNA methylation microarrays. The R132C IDH1 mutation was detected in 4/166 cancers. All IDH1 mutations were in CIMP cancers that were BRAF mutant and microsatellite stable (4/45, 8.9%). Unsupervised hierarchical cluster analysis identified an IDH1 mutation-like methylation signature in approximately half of the CIMP-positive cancers. IDH1 mutation appears to cause CIMP in a small proportion of BRAF mutant, microsatellite stable colorectal cancers. This study provides a precedent that a single gene mutation may cause CIMP in colorectal cancer, and that this will be associated with a specific epigenetic signature and clinicopathological features.     

三种兰科植物的保护遗传学研究初探

采用随机扩增多态 DNA(RAPD)分析研究了中国3种珍稀濒危兰科植物硬叶兜兰(Paphiopedilum micranthum Tang et Wang)、麻栗坡兜兰(P. malipoense S.C.Chen et Tsi)和独花兰(Changnienia amoena Chien)的遗传多样性与群体遗传结构.12个RAPD引物在2种兜兰中共扩增出131条带.对4个硬叶兜兰群体的检测表明其物种水平的多态条带百分率(PPB)为 71.6%,Nei 的基因多样度(h)为 0.217 1,Shannon多样性指数 (I) 为 0.330 1;4个群体的平均多样性水平为 PPB = 45.2%,h = 0.145 7,I = 0.220 4,低于远交兰花的平均水平.在总遗传变异中,群体间遗传变异占20.31%,略高于远交物种的平均水平.在物种水平上,麻栗坡兜兰的PPB为49.5%,h为0.117 4,I为0.176 4,均大大低于硬叶兜兰.对11个独花兰群体采用16个RAPD引物共扩增出119条带.物种水平PPB=76.5%,h=0.194 1,I=0.305 8;在群体水平上,上述3个指标的平均值则分别为37.2%、0.119 7和0.181 0,均低于远交兰花的平均水平.群体间的遗传变异占45.27%,遗传分化明显高于远交物种的平均水平.导致3个物种遗传多样性偏低而群体间遗传分化较高的主要原因在于人为的过度采挖和生境的片断化.研究结果为兰花保护策略和措施的制定提供了理论基础.     

柠檬酸合酶的分子生物学研究进展

柠檬酸合酶（citrate synthase,CS）是细胞内多种重要代谢途径的关键酶。CS可催化草酰乙酸和乙酰辅酶A之间的缩合反应生成柠檬酸和辅酶A。通常革兰氏阳性细菌、古菌以及真核细胞的CS为同源二聚体,而革兰氏阴性细菌的CS为同源六聚体。根据其在细胞内的定位不同,CS可分为线粒体CS、乙醛酸循环体CS、过氧化物酶体CS。这些同工酶在能量代谢、植物脂肪的代谢、脂肪酸的氧化及细胞解毒过程中起着重要作用。不同来源的CS空间结构、催化机制和动力学性质十分相似。针对其生化特性、空间结构特点、催化机制以及分子进化等研究进展进行综述。     

Characterisation of Structures in Salivary Secretion Film Formation. An Experimental Study with Atomic Force Microscopy

The purpose of the present study was to characterise the structure dynamics of pure salivary secretions retained on controlled surfaces with different surface energies in the early stage of salivary film formation. Germanium prisms prepared to have either low surface energy or medium surface energy were incubated in fresh secretions of either human parotid saliva (HPS) or human submandibular/sublingual saliva (HSMSLS) for 15, 90, and 180 min. After controlled rinsing with distilled water, the surfaces were air dried and thereafter imaged with atomic force microscopy (AFM). The amount of adsorbed material and the size of the structures detected increased with increased saliva exposure time. The film thicknesses varied from 10 to 150 nm, and both HPS and HSMSLS films contained structures with diameters varying from 40 nm to 2 μm. Some of these were clustered into special formations. The HPS films exhibited a more granular morphology than the HSMSLS films. Furthermore, branched lines were detected on the low surface energy germanium prisms incubated in saliva. The results indicate that exposure time, surface energy, and type of salivary secretion all are factors affecting the adsorption characteristics of salivary films.     

Optogenetic fUSI for brain-wide mapping of neural activity mediating collicular-dependent behaviors

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Protease nexin-2/amyloid beta-protein precursor in blood is a platelet-specific protein

The protease inhibitor, protease nexin-2 (PN-2), is the secreted form of the amyloid beta-protein precursor (APP) which contains the Kunitz protease inhibitor domain. PN-2/APP is an abundant platelet alpha-granule protein which is secreted upon platelet activation. PN-2/APP mRNA is present in cultured endothelial cells and the protein has been detected in plasma. In the present studies we quantitated PN-2/APP in platelets, plasma and several different cell types of the vasculature to identify the repository of the protein in the circulatory system. We report that PN-2/APP is predominantly a platelet protein in the vascular compartment. Lysates of unstimulated umbilical vein endothelial cells, granulocytes or monocytes contained little PN-2/APP based on sensitive functional protease binding and immunoblotting assays. Quantitative immunoblotting studies demonstrated that normal citrated-plasma contains less than or equal to 60 pM PN-2/APP. In contrast, platelets can contribute up to 30 nM PN-2/APP, indicating that they are the major source of the protein in blood.