人干扰素epsilon(IFN-ε)研究进展

人干扰素epsilon(IFN-ε)属于Ⅰ型干扰素,具有抗病毒、抗肿瘤、免疫调节等生物学作用,目前国内外对其研究不多,是一种有待开发的新型干扰素。本文就IFN-ε的基因结构、表达方式、表达位置、受体、受体配体的作用途径、生物学作用以及临床应用的前景等方面,进行了比较系统的归纳和总结。     

从alpha干扰素向epsilon干扰素发展

一种新型的人干扰素已被Daman Biotech公司分离出来,据最近的欧洲专利透露。epsilon表示该干扰素来自上皮组织,而不是根据被发现的先后次序所定的序号。     

Gamma–epsilon Interactions Regulate the Chloroplast ATP Synthase

Current literature on the structure and function of the chloroplast ATP synthase is reviewed with an emphasis on the roles of the gamma and epsilon subunits. Together these two subunits are thought to couple, via rotation, the proton motive force to nucleotide synthesis and hydrolysis by the catalytic F(1) segment of the enzyme. These two subunits are also responsible for inducing the latent state of the enzyme that is necessary to prevent futile hydrolysis of ATP in the dark when electron transfer and ATP synthesis are inactive. A model is presented to explain how gamma and epsilon interact to achieve the transition between the active and latent states.     

The 3′→5′ exonuclease associated with HeLa DNA polymerase epsilon

The 3′→5′ exonuclease activity of highly purified large form of human DNA polymerase epsilon was studied. The activity removes mononucleotides from the 3′ end of an oligonucleotide with a non-processive mechanism and leaves 5′-terminal trinucleotide non-hydrolyzed. This is the case both with single-stranded oligonucleotides and with oligonucleotides annealed to complementary regions of M13DNA. However, the reaction rates with single-stranded oligonucleotides are at least ten-fold when compared to those with completely base-paired oligonucleotides. Conceivably, mismatched 3′ end of an oligonucleotide annealed to M13DNA is rapidly removed and the hydrolysis is slown down when double-stranded region is reached. The preferential removal of a non-complementary 3′ end and the non-processive mechanism are consistent with anticipated proofreading function. In addition to the 3′→5′ exonuclease activity, an 5′→3′ exonuclease activity is often present even in relatively highly purified DNA polymerase epsilon preparates suggesting that such an activity may be an essential com-ponent for the action of this enzymein vivo. Contrary to the 3′→5′ exonuclease activity, the 5′→3′ exonuclease is separable from the polymerase activity.     

The 3′→5′ exonuclease associated with HeLa DNA polymerase epsilon

The 3′→5′ exonuclease activity of highly purified large form of human DNA polymerase epsilon was studied. The activity removes mononucleotides from the 3′ end of an oligonucleotide with a non-processive mechanism and leaves 5′-terminal trinucleotide non-hydrolyzed. This is the case both with single-stranded oligonucleotides and with oligonucleotides annealed to complementary regions of M13DNA. However, the reaction rates with single-stranded oligonucleotides are at least ten-fold when compared to those with completely base-paired oligonucleotides. Conceivably, mismatched 3′ end of an oligonucleotide annealed to M13DNA is rapidly removed and the hydrolysis is slown down when double-stranded region is reached. The preferential removal of a non-complementary 3′ end and the non-processive mechanism are consistent with anticipated proofreading function. In addition to the 3′→5′ exonuclease activity, an 5′→3′ exonuclease activity is often present even in relatively highly purified DNA polymerase epsilon preparates suggesting that such an activity may be an essential com-ponent for the action of this enzymein vivo. Contrary to the 3′→5′ exonuclease activity, the 5′→3′ exonuclease is separable from the polymerase activity.     

IκB kinase epsilon expression in adipocytes is upregulated by interaction with macrophages

Macrophage infiltration in the adipose tissue, and the interaction with adipocytes, is well documented to be involved in fat inflammation and obesity-associated complications. In this study, we isolated IκB kinase ε (IKKε) as a key adipocyte factor that is potentially affected by interaction with macrophages in adipose tissue in vivo. We showed that IKKε mRNA expression levels in white adipose tissue were increased in both genetic and diet-induced obese mouse. Furthermore, IKKε mRNA expression was decreased by the administration of vitamin B6, an anti-inflammatory vitamin, and that IKKε expression levels in adipose tissue were closely correlated with the numbers of infiltrating macrophages. In a co-culture system, we showed that IKKε expression in adipocytes was upregulated by interaction with activated macrophages. This study provides novel insight into IKKε, which is involved in adipose tissue inflammation during the development of obesity.     

人lambda1和epsilon干扰素基因在WI-38细胞中的表达及其活性比较

研究新型干扰素hIFN-λ1和hIFN-ε基因在WI-38细胞中的表达及其生物学活性,并进行对比分析。构建His重组融合表达载体pcDNA3.1A-hIFN-λ1-His和pcDNA3.1A-hIFN-ε-His,脂质体法分别转染WI-38人胚肺细胞。采用微量细胞病变抑制试验研究和比较rhIFN-λ1-His和rhIFN-ε-His的抗病毒活性;MTT法检测其对肿瘤细胞生长的影响; RT-PCR相对定量法检测其诱导WI-38和SHG-44细胞产生人MxA抗病毒蛋白的活性。结果表明rhIFN-λ1-His抗病毒活性、抗肿瘤细胞增殖活性和诱导产生MxA蛋白活性要强于rhIFN-ε-His。hIFN-λ1和hIFN-ε干扰素的抗病毒效应的分子机理均与诱导细胞产生MxA抗病毒蛋白相关。为进一步探讨和比较hIFN-λ1和hIFN-ε的生物学活性及其作用机制奠定了一定的基础。     

Activation of corticotropin-releasing factor 2 receptor inhibits Purkinje neuron P-type calcium currents via Goα-dependent PKC epsilon pathway

Corticotropin-releasing factor (CRF) receptors have been demonstrated to be widely expressed in the central nervous system and in many peripheral tissues of mammalians. However, it is still unknown whether CRF receptors will function in cerebellar Purkinje neurons. In the present study, we investigated the expression profile of CRF receptors in rat cerebellum and identified a novel functional role of CRFR2 in modulating Purkinje neuron P-type Ca²⁺ currents (P-currents). We found that CRFR2α mRNA, but not CRFR1 and CRFR2β, was endogenously expressed in rat cerebellum. Activation of CRFR2 by UCN2 inhibited P-currents in a concentration-dependent manner (IC₅₀ ~ 0.07 µM). This inhibitory effect was abolished by astressin2B, a CRFR2 antagonist, and was blocked by GDP-β-S, pertussis toxin, or a selective antibody raised against the G_oα. Inhibition of phospholipase C (PLC) blocked the inhibitory action of UCN2. The application of diacylglycerol (DAG) antagonist, 1-hexadecyl-2-acetyl-sn-glycerol, as well as inhibition of either protein kinase C or its epsilon isoform (PKCε) abolished the UCN2 effect while 1-oleoyl-2-acetyl-sn-glycerol (EI-150), a membrane-permeable DAG analogue, occluded UCN2-mediated inhibition. In addition, UCN2 significantly increases spontaneous firing frequency of Purkinje neurons in cerebellar slices. In summary, activation of CRFR2 inhibits P-currents in Purkinje neurons via G_oα-dependent PLC/PKCε pathway, which might contribute to its physiological functions in the cerebellum.     

Regulation of cell adhesion to collagen via β1 integrins is dependent on interactions of filamin A with vimentin and protein kinase C epsilon

Cell adhesion and spreading on collagen, which are essential processes for development and wound healing in mammals, are mediated by β1 integrins and the actin and intermediate filament cytoskeletons. The mechanisms by which these separate cytoskeletal systems interact to regulate β1 integrins and cell spreading are poorly defined. We previously reported that the actin cross-linking protein filamin A binds the intermediate filament protein vimentin and that these two proteins co-regulate cell spreading. Here we used deletional mutants of filamin A to define filamin A-vimentin interactions and the subsequent phosphorylation and re-distribution of vimentin during cell spreading on collagen. Imaging of fixed and live cell preparations showed that phosphorylated vimentin is translocated to the cell membrane during spreading. Knockdown of filamin A inhibited cell spreading and the phosphorylation and re-distribution of vimentin. Knockdown of filamin A and/or vimentin reduced the cell surface expression and activation of β1 integrins, as indicated by immunoblotting of plasma membrane-associated proteins and shear force assays. In vitro pull-down assays using filamin A mutants showed that both vimentin and protein kinase C? bind to repeats 1-8 of filamin A. Reconstitution of filamin-A-deficient cells with full-length filamin A or filamin A repeats 1-8 restored cell spreading, vimentin phosphorylation, and the cell surface expression of β1 integrins. We conclude that the binding of filamin A to vimentin and protein kinase Cε is an essential regulatory step for the trafficking and activation of β1 integrins and cell spreading on collagen.     

Syntheses of (±)-Epoformin (Desoxyepoxydon) and (±)-Epiepoformin (Desoxyepiepoxydon)

Boron is an essential nutrient for plants, but it is toxic in excess. Transgenic rice plants expressing an Arabidopsis thaliana borate efflux transporter gene, AtBOR4, at a low level exhibited increased tolerance to excess boron. Those lines with high levels of expression exhibited reduced growth. These findings suggest a potential of the borate transporter BOR4 for the generation of high-boron tolerant rice.     

红豆杉(Taxus chinensis (Pilger) Rehd.)化学成分研究(简报)

自七十年代发现了紫杉醇（taxol）独特的抗癌机制一促进微管蛋白聚合、抑制微管蛋白解聚后,紫杉醇及其类似物紫杉烷类二该化合物的资源调查和化学研究倍受重视。紫杉醇主要存在于红豆杉科的大多数植物中,红豆杉科（Taxaceae）红豆杉属（TaxuS）植物全球大约有11种,我国有4种和1个变种。我们从采自湖北神农架的红豆杉（Tchinens周树皮中分离得到8个结晶性物质,本文报道其中已鉴定的3个成分,即taxinineJ（l）,ldiydroxybaccatinl（2）和taxol（3）。据文献报道,已经从红豆杉分离得到二十多种紫杉烷类化合物l'l,而我们分离得到的1和2…     

生理卫生(下册)教学参考资料(续完)

第三节祖国在防治疾病上的伟大成就这节课是在学生已掌握了传染病的基本知識的基础上来进行講授的,首先在教材里提出以血吸虫病、天花、瘧疾、黑热病、痳疯等传染病說明了新旧社会的对比;同时也说明了社会主义社会制度的优越性。我們的党和政府对于人民健康的关怀是无微不至的,并且对于各种疾病的积极防治工作加强了党的领导,及时提出了一系列的方針、政策和措施;建立了专业防治机构,培养了专业干部;結合生产发动了广大羣众来参加防治。因此在防治各种传染病的工作中取得了很大的成績。     

生理卫生(下册)教学参考资料(续)

第五节大脑皮层的机能——高级神經活动本节是本章也是本書的高峯,是把过去学习过有关反射作用的知識进行总結和提高,使学生能从理論上理解神经对人的意义——保持內部各器官的协調,同外界环境的统一。     

IR and Raman study on the interactions of the 5′-GMP and 5′-CMP phosphate groups with Mg(II), Ca(II), Sr(II), Ba(II), Cr(III), Co(II), Cu(II), Zn(II), Cd(II), Al(III) and Ga(III)

The chief motive behind this research is the interest provoked by the presence of metal ions as necessary stabilizers of the negative charges of phosphate groups in nucleic acids. The effect that the presence of different metal ions produces on the band principally assigned to the nu(s) PO(3)(2-) mode has been studied using FT-IR and FT-Raman spectroscopy. The results obtained reveal the diagnostic capacity of these techniques in determining the type of metal ion interaction with respect to the mononucleotides that form DNA and RNA, providing a tool for improving the knowledge of the stabilizing or destabilizing effects of these ions on such macromolecules. The metal complexes of the ribonucleotides 5'-CMP and 5'-GMP with Mg(II), Ca(II), Sr(II), Ba(II), Cr(III), Co(II), Cu(II), Zn(II), Cd(II), Al(III) and Ga(III) were obtained in this study. After studying and analyzing the IR and Raman spectra of all these complexes and comparing them with the spectra of the corresponding disodium salts, it was verified that, independently of the type of nucleotide involved, the presence of the metal in the vicinity of the phosphate group produces an alteration in the aforementioned nu(s) PO(3)(2-) band. This effect is related to the type of interaction that the phosphate group has with the metal. Three components are observed: (1) one near 983-975 cm(-1) (detectable in IR and Raman), associated with phosphate groups in an electrostatic type of interaction with the metal ion, separated by two or more water molecules; (2) another near 989-985 cm(-1) (only in IR), associated with phosphate groups in indirect interaction through the water molecules of the coordination sphere of the metal ions; and (3) the IR and Raman bands near 1014-1001 cm(-1), which represent phosphate groups directly bonded to the metal ion. These results are supported by the behavior of 5'-CMP in aqueous solution in the presence of Mg(II) ions.     

Robert (Robin) Hill (1899–1991)

Obituary

Robert (Robin) Hill (1899–1991)     

The Zhoukoudian (Choukoutien) Site(英汉对照)

ＴｈｅＺｈｏｕｋｏｕｄｉａｎ（Ｃｈｏｕｋｏｕｔｉｅｎ）Ｓｉｔｅ（英汉对照）ＴｈｅＺｈｏｕｋｏｕｄｉａｎＳｉｔｅ,ｆａｍｏｕｓ“ｈｏｍｅ”ｏｆＰｅｋｉｎｇＭａｎ,ｌｉｅｓａｐｐｒｏｘｉｍａｔｅｌｙ５０ｋｉｌｏｍｅｔｒｅｓｓｏｕｔｈｗｅｓｔｏｆｔｈｅＰｅ...     

Apanteles Pieridis (bouché) (Hym., Braconidae), ein Parasit vonAporia Crataegi (L.) (Lep., Pieridae)

Ohne Zusammenfassung     

平滑肌内向整流钾通道(K_(IR))

平滑肌内向整流钾通道在维持和调节细胞膜电位中发挥重要作用,并可能成为新的治疗靶点.综述了其分子学基础、电生理特性、生理功能和调控机理等研究进展.