肺纤维化初期肺动脉高压大鼠肺动脉反应性的变化

目的：观察肺纤维化初期肺动脉高压大鼠肺动脉血管反应性的变化。方法：66只雄性SD大鼠,随机分为博莱霉素（BLM）组和手术对照（Sham）组。BLM组为气管内一次性滴注BLM（5 mg/kg）;Sham组为气管内滴注等容量的生理盐水（NS）。应用离体血管张力检测技术测定大鼠肺动脉血管反应性变化;用HE显示肺动脉壁病理形态学变化;Masson染色检测肺纤维化程度;右心漂浮导管技术测定大鼠平均肺动脉压。结果：①BLM组大鼠的肺动脉血管（保留内皮和去内皮）对苯肾上腺素（PE）的收缩反应均弱于Sham组（P均〈0.05）。②BLM组大鼠肺动脉血管（保留内皮）对氯化乙酰胆碱（Ach）的舒张反应明显弱于Sham组（P〈0.01）。③Sham组有内皮的肺动脉血管对L-NAME和PE联合作用的收缩反应明显强于PE单独作用（P〈0.01）,而BLM组有内皮肺动脉血管对L-NAME和PE联合作用的收缩反应与对PE单独作用比,其差异无统计学意义（P〉0.05）。④BLM组肺动脉内皮细胞脱落。⑤BLM组大鼠肺组织呈现纤维增生初期的病理特征,且大鼠的平均肺动脉压明显高于Sham组（P〈0.05）。结论：肺纤维化形成初期肺动脉高压大鼠肺动脉血管反应性出现异常。     

<Emphasis Type="Italic">Pseudomonas stutzeri</Emphasis> as a novel biocatalyst for pyruvate production from<Emphasis Type="SmallCaps"> DL</Emphasis>-lactate

Pseudomonas stutzeri SDM oxidized dl-lactic acid (25.5 g l^-1) into pyruvic acid (22.6 g l^-1) over 24 h. Both NAD⁺-independent d-lactate dehydrogenase and NAD⁺-independent l-lactate dehydrogenase were found for the first time in the bioconversion of lactate to pyruvate based on the enzyme activity assay and proteomic analysis. Jianrong Hao and Cuiqing Ma contributed equally to this work     

Mutation discovery in mice by whole exome sequencing

We report the development and optimization of reagents for in-solution, hybridization-based capture of the mouse exome. By validating this approach in a multiple inbred strains and in novel mutant strains, we show that whole exome sequencing is a robust approach for discovery of putative mutations, irrespective of strain background. We found strong candidate mutations for the majority of mutant exomes sequenced, including new models of orofacial clefting, urogenital dysmorphology, kyphosis and autoimmune hepatitis.     

Human Ago2 is required for efficient microRNA 122 regulation of hepatitis C virus RNA accumulation and translation

MicroRNA 122 (miR-122) increases the accumulation and translation of hepatitis C virus (HCV) RNA in infected cells through direct interactions with homologous sequences in the 5' untranslated region (UTR) of the HCV genome. Argonaute 2 (Ago2) is a component of the RNA-induced silencing complex (RISC) and mediates small interfering RNA (siRNA)-directed mRNA cleavage and microRNA translational suppression. We investigated the function of Ago2 in HCV replication to determine whether it plays a role in enhancing the synthesis and translation of HCV RNA that is associated with miR-122. siRNA-mediated depletion of Ago2 in human hepatoma cells reduced HCV RNA accumulation in transient HCV replication assays. The treatment did not adversely affect cell viability, as assessed by cell proliferation, capped translation, and interferon assays. These data are consistent with complementary roles for Ago2 and miR-122 in enhancing HCV RNA amplification. By using a transient HCV replication assay that is dependent on an exogenously provided mutant miR-122, we determined that Ago2 depletion still reduced luciferase expression and HCV RNA accumulation, independently of miR-122 biogenesis. miR-122 has previously been found to stimulate HCV translation. Similarly, Ago2 knockdown also reduced HCV translation, and its depletion reduced the ability of miR-122 to stimulate viral translation. These data suggest a direct role for Ago2 in miR-122-mediated translation. Finally, Ago2 was also necessary for efficient miR-122 enhancement of HCV RNA accumulation. These data support a model in which miR-122 functions within an Ago2-containing protein complex to augment both HCV RNA accumulation and translation.     

Protein kinase B/Akt may regulate G2/M transition in the fertilized mouse egg by changing the localization of p21(Cip1/WAF1)

Protein kinase B (PKB, also called Akt) is known as a serine/threonine protein kinase. Some studies indicate that the Akt signalling pathway strongly promotes G2/M transition in mammalian cell cycle progression, but the mechanism remains to be clarified, especially in the fertilized mouse egg. Here, we report that the expression of Akt at both the protein and mRNA level was highest in G2 phase, accompanied by a peak of Akt activity. In addition, the subcellular localization of p21(Cip1/WAF1) has been proposed to be critical in the cell cycle. Hence, we detected the expression and localization of p21(Cip1/WAF1) after injecting fertilized mouse eggs with Akt mRNA. In one-cell stage fertilized embryos microinjected with mRNA coding for a constitutively active myristoylated Akt (myr-Akt), p21(Cip1/WAF1) was retained in the cytoplasm. Microinjection of mRNA of kinase-deficient Akt(Akt-KD) resulted in nuclear localization of p21(Cip1/WAF1) . Meanwhile, microinjection of different types of Akt mRNA affected the phosphorylation status of p21(Cip1/WAF1) . However, there was no obvious difference in the protein expression of p21(Cip1/WAF1) . Therefore, Akt controls the cell cycle by changing the subcellular localization of p21(Cip1/WAF1) , most likely by affecting the phosphorylation status of p21(Cip1/WAF1) .     

Overexpression in tobacco of a tomato GMPase gene improves tolerance to both low and high temperature stress by enhancing antioxidation capacity

GDP-mannose pyrophosphorylase (GMPase: EC 2.7.7.22) plays a crucial role in the synthesis of l-ascorbate (AsA) and the consequent detoxification of reactive oxygen species (ROS). Herein, a GMPase (accession ID DQ449030) was identified and cloned from tomato. The full-length cDNA sequence of this gene contains 1,498 bp nucleotides encoding a putative protein with 361 amino acid residues of approximate molecular weight 43 kDa. Northern blot analysis revealed that the GMPase was expressed in all examined tomato tissues, but its expression level was up-regulated in tomato plants subjected to abnormal temperatures. We then overexpressed this tomato GMPase in tobacco plants and observed that the activity of GMPase and the content of AsA were significantly increased by two- to fourfold in the leaves of transgenic tobacco plants. The effect of this gene overexpression was superimposed by the treatments of high or low temperature in tobacco, since the activities of both chloroplastic SOD (superoxide dismutase EC 1.15.1.1), APX (ascorbate peroxidase EC 1.11.1.7) and the content of AsA in leaves were significantly higher in transgenic plants than those of WT, while the contents of H₂O₂ and O₂ ^−· were reduced. Meanwhile, relative electric conductivity increased less in transgenic plants than that in WT, and the net photosynthetic rate (P _n) and the maximal photochemical efficiency of PSII (F _v/F _m) of transgenic plants were notably higher than those of WT under temperature stresses. In conclusion, the overexpression of GMPase increased the content of AsA, thereby leading to the increase in tolerance to temperature stress in transgenic plants.     

中国11个双子叶植物原白中排印错误之更正

对我国11个双子叶植物（Dicotyledon）原白中模式标本引证的排印错误做了更正：砚山锥栗（壳斗科）原白中错误地将模式标本引证为王启无84116,实际应为王启无84416,前者属于菊科植物Inuna helianthus-aquatica C.Y.Wu ex Ling。长果柯（壳斗科）原白中错误地将模式标本引证为K.M.Feng 13012,实际应为K.M.Feng 13102,前者属于冬青科植物Ilex triflora Bl.。福建红小麻（荨麻科）原白中错误地将主模式标本引证为C.J.Chen&Z.Y.Li 109,实际应为C.J.Chen&Z.Y.Li 103,前者属于荨麻科植物Oreocnide frutescens（Thunb.）Miq.。少毛全缘叶紫麻（荨麻科）原白中错误地将主模式标本引证为N.K.Chun 44099,实际应为N.K.Chun 44033,前者属于杜鹃花科植物Lyonia ovalifolia（Wallich）Drude var.rubrovenia（Merr.）Judd.。甘南铁线莲（毛茛科）原白中错误地将主模式标本引证为Baishuijiang Exped.4490,实际应为Baishuijiang Exped.4990,前者属于卫矛科植物Euonymus alatus（Thunb.）Sieb.。矮粗距翠雀花（毛茛科）原白中错误地将模式标本引证为Sichuan Veg.Exped.3137,实际应为Sichuan Veg.Exped.3173,前者属于龙胆科植物Gentiana conduplicata T.N.Ho。镇康黄芪（豆科）原白中错误地将主模式标本引证为T.T.Yu 17255,实际应为T.T.Yu 17225,前者属于莎草科植物Scirpus lushanensis Ohwi。宽翼棘豆（豆科）原白中错误地将模式标本引证为Qinghai-Xizang Comp.Exped.9484,实际应为Qinghai-Xizang Comp.Exped.9485,前者属于石竹科植物Arenaria kansuensis Maxim.。肾瓣黄芪（豆科）原白中错误地将模式标本引证为Qinghai-Xizang Comp.Exped.3650,实际应为Qinghai-Xizang Comp.Exped.3605,前者属于麻黄科植物Ephedra gerardiana Wall.ex Mey.。湖南长柄槭（槭树科）原白中错误地将模式标本引证为李泽棠2944,实际应为李泽棠2994,前者属于杜鹃花科植物Pieris formosa D.Don。峨眉勾儿茶（鼠李科）原白中错误地将模式标本引证为杨光辉54729,实际应为杨光辉54723,前者属于山茱萸科植物Helwingia chinensis Batalin.。     

hPNAS-4 inhibits proliferation through S phase arrest and apoptosis: underlying action mechanism in ovarian cancer cells

PNAS-4, a novel pro-apoptotic gene, was activated during the early response to DNA damage. Previous studies have shown that hPNAS-4 can inhibit tumor growth when over-expressed in ovarian cancer cells. However, the underlying action mechanism remains elusive. In this work, we found that hPNAS-4 expression was significantly increased in SKOV3 cells when exposed to cisplatin, methyl methanesulfonate or mitomycin C, and that its overexpression could induce proliferation inhibition, S phase arrest and apoptosis in A2780s and SKOV3 ovarian cancer cells. The S phase arrest caused by hPNAS-4 was associated with up-regulation of p21. p21 is p53-dispensable and correlates with activation of ERK, and activation of the Cdc25A-Cdk2-Cyclin E/Cyclin A pathway, while the pro-apoptotic effects of hPNAS-4 were mediated by activation of caspase-9 and -3 other than caspase-8, and accompanied by release of AIF, Smac and cytochrome c into the cytosol. Taken together, these data suggest a new mechanism by which hPNAS-4 inhibits proliferation of ovarian cancer cells by inducing S phase arrest and apoptosis via activation of Cdc25A-Cdk2-Cyclin E/Cyclin A axis and mitochondrial dysfunction-mediated caspase-dependent and -independent apoptotic pathways. To our knowledge, we provide the first molecular evidence for the potential application of hPNAS-4 as a novel target in ovarian cancer gene therapy.