Variation in the DEPDC5 locus is associated with progression to hepatocellular carcinoma in chronic hepatitis C virus carriers

Chronic viral hepatitis is the most important risk factor for progression to hepatocellular carcinoma (HCC). To identify genetic risk factors for progression to HCC in individuals with chronic hepatitis C virus (HCV), we analyzed 467,538 SNPs in 212 Japanese individuals with chronic HCV with HCC and 765 individuals with chronic HCV without HCC. We identified one intronic SNP in the DEPDC5 locus on chromosome 22 associated with HCC risk and confirmed the association using an independent case-control population (710 cases and 1,625 controls). The association was highly significant when we analyzed the stages separately as well as together (rs1012068, P(combined) = 1.27 × 10(-13), odds ratio = 1.75). The significance level of the association further increased after adjustment for gender, age and platelet count (P = 1.35 × 10(-14), odds ratio = 1.96). Our findings suggest that common variants within the DEPDC5 locus affect susceptibility to HCC in Japanese individuals with chronic HCV infection.     

Blue emission from hydrogen-containing a-Si：H／SiO2 multilayers and the investigation of its mechanism

A series of hydrogen-containing a-Si:H/SiO2 multilayers with different a-Si:H sublayer thickness were fabricated by layer-by-layer deposition and in situ plasma oxidation in a plasma-enhanced chemical vapor deposition system (PECVD). Optical induced blue emission from the samples was observed by the naked eye at room temperature, which has never been reported in the luminescence study of Si/SiO2 multilayers up to now. Both the photoluminescence (PL) peak and the absorption edge show a blue shift as the a-Si:H sublayer thickness decreases. The origin of the blue emission and the effect of hydrogen are discussed.     

Fras1 deficiency results in cryptophthalmos,renal agenesis and blebbed phenotype in mice

Loss of tight association between epidermis and dermis underlies several blistering disorders and is frequently caused by impaired function of extracellular matrix (ECM) proteins. Here we describe a new protein in mouse, Fras1, that is specifically detected in a linear fashion underlying the epidermis and the basal surface of other epithelia in embryos. Loss of Fras1 function results in the formation of subepidermal hemorrhagic blisters as well as unilateral or bilateral renal agenesis during mouse embryogenesis. Postnatally, homozygous Fras1 mutants have fusion of the eyelids and digits and unilateral renal agenesis or dysplasia. The defects observed in Fras1-/- mice phenocopy those of the existing bl (blebbed) mouse mutants, which have been considered a model for the human genetic disorder Fraser syndrome. We show that bl/bl homozygous embryos are devoid of Fras1 protein, consistent with the finding that Fras1 is mutated in these mice. In sum, our data suggest that perturbations in the composition of the extracellular space underlying epithelia could account for the onset of the blebbed phenotype in mouse and Fraser syndrome manifestation in human.     

Haploinsufficiency of NSD1 causes Sotos syndrome

We isolated NSD1 from the 5q35 breakpoint in an individual with Sotos syndrome harboring a chromosomal translocation. We identified 1 nonsense, 3 frameshift and 20 submicroscopic deletion mutations of NSD1 among 42 individuals with sporadic cases of Sotos syndrome. The results indicate that haploinsufficiency of NSD1 is the major cause of Sotos syndrome.     

Periostin in inflammation and allergy

We found for the first time that IL-4 and IL-13, signature type 2 cytokines, are able to induce periostin expression. We and others have subsequently shown that periostin is highly expressed in chronic inflammatory diseases―asthma, atopic dermatitis, eosinophilc chronic sinusitis/chronic rhinosinusitis with nasal polyp, and allergic conjunctivitis—and that periostin plays important roles in the pathogenesis of these diseases. The epithelial/mesenchymal interaction via periostin is important for the onset of allergic inflammation, in which periostin derived from fibroblasts acts on epithelial cells or fibroblasts, activating their NF-κB. Moreover, the immune cell/non-immune cell interaction via periostin may be also involved. Now the significance of periostin has been expanded into other inflammatory or fibrotic diseases such as scleroderma and pulmonary fibrosis. The cross-talk of periostin with TGF-β or pro-inflammatory cytokines is important for the underlying mechanism of these diseases. Because of its pathogenic importance and broad expression, diagnostics or therapeutic drugs can be potentially developed to target periostin as a means of treating these diseases.     

短双歧杆菌(Bifidobacterium breve 203)α-D-半乳糖苷酶的诱导合成及部分酶性质研究

研究发现 2 5株所试肠道细菌中只有 6株双歧杆菌可以利用棉子糖良好生长 ,并且在棉子糖的诱导下产生α D 半乳糖苷酶 .9种不同糖中 ,Bifidobacter iumbreve 2 0 3可以利用葡萄糖、半乳糖、果糖、麦芽糖、乳糖、蜜二糖、棉子糖良好生长 ,但只有蜜二糖和棉子糖诱导α D 半乳糖苷酶的产生 .1 0mmol/L的棉子糖和蜜二糖对于α D 半乳糖苷酶的诱导合成是最佳浓度的 ,且此浓度下 ,棉子糖的诱导能力 (比活 7.1 3units/mg)是蜜二糖 (比活 3 .4 0units/mg)的 2倍以上 .B .breve 2 0 3菌株α D 半乳糖苷酶专一性水解α D 半乳糖苷键 ,不水解β D 半乳糖苷键 .酶反应的最适温度是 3 7℃ ,酶在 4 0℃以下稳定 ,60℃时剩余 80 %的酶活 ,65℃时剩余 2 0 %的酶活 ,70℃时失去所有的酶活 .酶在 pH5.5～ 9.5稳定 ,酶反应的最适pH是 5.5～ 6.5.Hg 、Cu2 、Ag 和PCMB强烈抑制酶的活性 ,而Co2 、Mg2 、Ca2 、Mn2 、Zn2 、EDTA和DTT对酶活性没有抑制 .     

Structural changes of deoxyribonucleoprotein fibres following gamma-irradiation under aerobic and hypoxic conditions.

The DNP fibres gamma-irradiated under aerobic condition showed a reduction of their diameter, while no remarkable changes were observed in the DNP fibres irradiated under hypoxic condition by scanning electron microscopy.     

一种基于度量距离学习的图像检索方法

CBIR系统由于受图像低层特征的限制,制约了它的检索效果。机器学习和统计方法是一种有效的提高检索性能的方法,但通常需要大量的训练样本才能达到满意的检索精度。提出一种理想的距离度量函数,在对图像进行简单分类并提供少量训练样本的基础上,通过类的距离度量矩阵M的学习来考虑分量之间的相关性。这个度量导入二次最佳化问题的解,将训练样本类结构的倾斜最小化。试验结果表明,该方法能在学习样本极少的情况下提高检索的性能。     

Enzymatic catalysis of anti-Baldwin ring closure in polyether biosynthesis

Polycyclic polyether natural products have fascinated chemists and biologists alike owing to their useful biological activity, highly complex structure and intriguing biosynthetic mechanisms. Following the original proposal for the polyepoxide origin of lasalocid and isolasalocid and the experimental determination of the origins of the oxygen and carbon atoms of both lasalocid and monensin, a unified stereochemical model for the biosynthesis of polyether ionophore antibiotics was proposed. The model was based on a cascade of nucleophilic ring closures of postulated polyepoxide substrates generated by stereospecific oxidation of all-trans polyene polyketide intermediates. Shortly thereafter, a related model was proposed for the biogenesis of marine ladder toxins, involving a series of nominally disfavoured anti-Baldwin, endo-tet epoxide-ring-opening reactions. Recently, we identified Lsd19 from the Streptomyces lasaliensis gene cluster as the epoxide hydrolase responsible for the epoxide-opening cyclization of bisepoxyprelasalocid A to form lasalocid A. Here we report the X-ray crystal structure of Lsd19 in complex with its substrate and product analogue to provide the first atomic structure-to our knowledge-of a natural enzyme capable of catalysing the disfavoured epoxide-opening cyclic ether formation. On the basis of our structural and computational studies, we propose a general mechanism for the enzymatic catalysis of polyether natural product biosynthesis.