纪念卢衍豪老师

中国科学院院士、我们敬爱的老师卢衍豪教授 (1913- 2 0 0 0 )逝世已一年多了 ,但是他对科学事业的执着追求和奉献精神一直留在我们心中。我们深切缅怀他对我国地层古生物事业所作的杰出贡献。卢衍豪院士是国内外著名的古生物学家和地层学家 ,在我国和国际地学界享有崇高的声誉。卢衍豪教授 1913年出生于福建省永定县 ,1937年毕业于北京大学地质系 ,获理学学士学位。毕业后留校任助教 ,在葛利普和孙云铸教授的影响下 ,他从事三叶虫研究。在西南联大 (1938- 194 1)期间 ,他开始对我国西南地区早寒武世三叶虫研究 ,首次建立了我国下寒武统地层…     

磷酸二酯酶5（PDE5）在人增生前列腺移行带中的表达及分布

目的:探讨磷酸二酯酶5在人前列腺移行带组织中的表达与分布。方法:应用免疫组化SP法,选择前列腺增生患者34例,检测PDE5表达及分布。结果:34例标本中PDE5均呈阳性表达。PDE5在前列腺移行带的腺组织上皮普遍呈中等表达,间质部分弱表达。结论:PDE5在人增生前列腺组织中分布,但分布不均,表明不同PDE5可能行使不同的功能。     

Schizosaccharomyces pombe produces novel Gal0-2Man1-3 O-linked oligosaccharides

Schizosaccharomyces pombe whole-cell glycoproteins, previously depleted of N-linked glycans by sequential treatment with endo-ss-N-acetylglucosaminidase H and peptide-N4-asparagine amidohydrolase F, were ss-eliminated with 0.1 M NaOH/1 M NaBH4 to release the O-linked oligosaccharides. The saccharide-alditols were separated by gel-exclusion chromatography into pools from Hexitol to Hex4Hexitol in size. Analysis of the Hexitol pool indicated Man to be the only sugar linked to Ser or Thr residues. The Hex1Hexitol pool contained two components, Galalpha1,2Man-ol (2A) and Manalpha1, 2Man-ol (2B). The Hex2Hexitol pool contained two components, Galalpha1,2Manalpha1,2Man-ol (3A) and Manalpha1,2Manalpha1,2Man-ol (3B). The two Hex3Hexitol components were Galalpha1,2(Galalpha1, 3)Manalpha1,2Man-ol (4A) and Manalpha1,2(Galalpha1,3)Manalpha1, 2Man-ol (4B). The Hex4Hexitol component was found to be a single isomer with the composition of Galalpha1,2(Galalpha1,3)Manalpha1, 2Manalpha1,2Man-ol (5AB). Surprisingly, galactobiose was not detected in any of these oligosaccharides. The gma12 (T. G. Chappell and G. Warren (1989) J. Cell Biol., 109, 2693-2707) and gth1 (T. G. Chappell personal communication) alpha1, 2-galactosyltransferase-deficient mutants and the gma12/gth1 double mutant S.pombe strains were similarly examined. The results indicated that gma12p is solely responsible for the addition of terminal alpha1,2-linked Gal in compound 2A, while one or both of gma12p and gth1p are required for the alpha1,2-linked Gal in 4A. Both transferases are largely responsible for terminal Gal in isomer 5AB. Neither gma12 nor gth1 had any discernible effect on the structure of the large N-linked galactomannans as determined by 1H NMR spectroscopy. Thus, while gth1p and gma12p appear responsible for adding alpha1,2-linked Gal to terminal Man, neither adds galactose side chains to the N-linked poly alpha1,6-Man outerchain, nor the O-linked branch-forming alpha1,3-linked Gal. Furthermore, the presence of Hexalpha1,2(Galalpha1,3)Manalpha1,2- structures in the O-linked glycans implies the presence of a novel branch-forming alpha1,3-galactosyltransferase in S.pombe.     

金属蛋白酶-2(MMP-2)和金属蛋白酶抑制因子(TIMP-1,-3)mRNA在小鼠胎盘中的表达

本实验利用原位杂交对小鼠妊娠不同时期胎盘中MMP－2,TIMP－2,－3mRNA的表达进行了研究。结果表明;MMP－2主要在具有很强的侵润能力的海绵滋养层细胞中表达,到妊娠13．5天时,MMP－2的表达明显降低,说明此时的滋养层细胞基本上失去侵润能力。TMIP－1和TMIP－3在滋养层细胞和蜕膜细胞中都有表达,这两种抑制因子的协同表达,一方面能够调控滋养层细胞侵入子宫内膜的深度,另一方面,滋养层细胞自身既表达MMP－2又表达TIMPs,可能对其自身有保护作用,使得MMP的水解功能局限于子宫蜕膜的特定区域。在妊娠10．5天,滋养层巨细胞同时表达TIMP－1,－3mRNA,这可能与其功能的转换是一致的;因为此时小鼠滋养层巨细胞体积最大,且不再增殖,同时其功能屯从侵入型向内分泌型转换。所以,MMPs和TIMPs在小鼠滋养层细胞和子宫蜕膜中的协同表达表明其在着床过程中可能发挥重要作用。     

Rapid synthesis of 2-desoxy-2-amino-3-phosphocholine-glycerinic-acid- alkylester, 1-alkyl-1-desoxy- and 1-O-alkyl-2-desoxy-2-amino-sn-glycero-3- phosphocholines, -3-phospho-N,N'-dimethylethanolamine and -3-phospho-Fmoc- serine-methylester.

A convenient sequence for the rapid synthesis of 2-desoxy-2-amino-3-phosphocholine-glycerinic-acid-alkylester , 1-alkyl-1-desoxy- and 1-O-alkyl-2-amino-2-desoxy-3-phospho-derivatives is described. Key steps are the reaction of 1-carbonyloxyalkyl-, 1-alkyl- or 1-O-alkyl-amino-alcohols with phosphorus oxychloride to 1-carbonyloxyalkyl-, 1-alkyl- or 4-substituted 2-chloro-2-oxo-1,3,2-oxazaphospholane followed by nucleophilic displacement with choline tosylate, 1-bromoethane-2-ol or Fmoc-L-serine-methylester and subsequent hydrolysis to 2-amino-lysophospholipids giving the desired compounds in yields ranging between 68% and 81%. Several 2-amino-lysophospholipid analogs can then be prepared by this synthetic scheme utilizing the same oxazaphospholane intermediate. A brief method for the preparation of 2-amino-3-hydroxy-propionic-acid-pentyl- and -octylester from L-serine is described, opening a facile access to chiral precursors of phospholipid analogs.     

BMP-2、-3、-6和-12在骨肉瘤细胞株中的表达

目的研究骨形态发生蛋白(bone morphogenetic protein,BMP)-2、-3、-6和-12在骨肉瘤细胞株中的表达,为下一步研究BMPs在骨肉瘤发生发展中的作用奠定基础。方法利用免疫细胞化学法和Western blot法检测BMP-2、-3、-6和-12在人骨肉瘤细胞株MG63、U2OS和大鼠骨肉瘤细胞株UMR106中的内源性表达。结果在MG63、U2OS和UMR106细胞中,BMP-2、-3和-6均呈不同程度的阳性表达;而BMP-12在这3株骨肉瘤细胞中则均为阴性,并且两种检测方法所得结果完全一致。结论BMP-2、-3和-6在人骨肉瘤细胞株MG63、U2OS和大鼠骨肉瘤细胞株UMR106中均有内源性表达;而这3株骨肉瘤细胞中均未检出BMP-12的表达。     

Dkk1, -2, and -3 expression in mouse craniofacial development

Summary The Dickkopf family is important for embryogenesis and postnatal development and growth. Dkk1 is a strong head inducer and knockout of this gene leads to absence of anterior head structures, which are predominantly formed through neural crest migration. During early craniofacial development, Dkk1 to Dkk3 show developmentally regulated expression in a number of elements. However, their expression and roles in late times of craniofacial development are largely unknown. This study focuses on the expression profile of Dkk1-3 on late embryonic and early postnatal stages. It was found that Dkks were involved in a variety of craniofacial developmental processes, including facial outgrowth, myogenesis, osteogenesis, palatogenesis, olfactory epithelium and tooth development; and the expression persisted to postnatal stage in the muscles and bones. Their expression patterns suggest important roles in these processes; further study is warranted to elucidate these roles.     

Stimulation of human neutrophil degranulation with 1-0-octadecyl-2-0-acetyl-sn-glyceryl-3-phosphorylcholine: Modulation by inhibitors of arachidonic acid metabolism

1-0-octadecyl-2-0-acetyl-sn-glyceryl-3-phosphorylcholine (C₁₈-AGEPC) stimulated a concentration (10-¹⁰-10-⁶M)-dependent release of granule-associated enzymes from human neutrophils. Cells which were not preincubated with cytochalasin B prior to exposure to C₁₈-AGEPC did not degranulate. C₁₈-AGEPC-elicited enzyme release was significantly reduced, but not abolished, in the absence of extracellular calcium. The lipoxygenase inhibitor, nordihydroguaiaretic acid and the lipoxygenase/cyclo-oxygenase inhibitor, 5,8,11,14-eicosatetraynoic acid, an acetylenic analog of arachidonic acid, caused a concentration-dependent suppression of enzyme discharge from neutrophils exposed to C₁₈-AGEPC. However, the cyclo-oxygenase inhibitors, indomethacin, ibuprofen and flurbiprofen had no effect on C₁₈-AGEPC-induced enzyme extrusion.     

2-Substituted 4-, 5-, and 6-[(1E)-3-oxo-3-phenylprop-1-en-1-yl]pyridazin-3(2H)-ones and 2-substituted 4,5-bis[(1E)-3-oxo-3-phenylprop-1-en-1-yl]pyridazin-3(2H)-ones as potent platelet aggregation inhibitors: design, synthesis, and SAR studies

A set of regioisomeric 2-substituted pyridazin-3(2H)-ones containing a 3-oxo-3-phenylprop-1-en-1-yl fragment at either position 4, 5 or 6 and 2-substituted pyridazin-3(2H)-ones containing the same fragment both at positions 4 and 5 have been synthesized and evaluated as antiplatelet agents. The study allows the identification of a new highly potent platelet aggregation inhibitor (4c).     

Bioactive recombinant neuregulin-1, -2, and -3 expressed in Escherichia coli

The neuregulins (NRGs) are a family of signaling proteins that are ligands for receptor tyrosine kinase of the ErbB family (namely ErbB3 and ErbB4). To date, four different neuregulin genes have been identified (neuregulin1-4). While NRG1 isoforms have been extensively studied, little is yet known about the other genes of the family. We report the expression of recombinant NRG1beta1, NRG2alpha, NRG2beta, and NRG3 as recombinant fusion proteins in Escherichia coli. The cDNA encoding for the EGF-like domain of each protein was cloned from the mouse olfactory bulb and inserted into the pET-19b vector allowing for bacterial expression of the protein fused to an N-terminal His tag. The recombinant NRGs expressed in the inclusion bodies were solubilized under denaturing conditions, purified by affinity chromatography, and refolded via dialysis in the presence of reducing agents. Purified recombinant NRGs were active as they bound to their receptors and induced their phosphorylation. In particular, and in agreement with data on the native proteins, all the molecules were able to bind and activate ErbB4 while only the rNRG1 and the two rNRG2 (but not rNRG3) bound ErbB3.     

5-Fluoro-1-(3,4-dideoxy-3-fluoro-6-0-trityl-beta-D-glycero-hex-3-eno-pyranos-2-ulosyl (Uracil): Anticancer Agent

Abstract

1,2:5,6-Di-0-isopropylidene glucofuranose on mild oxidation, reduction, fluorination and deisopropylidenation followed by acetylation gave peracetylated 3-deoxy-3-fluoro-alpha-D-glucopyranose. This was coupled with silylated 5 fluorouracil. The nucleoside was deacetylated and after several subsequent protection and deprotection and final oxidation afforded the title compound.     

Solution conformation of asparagine-linked oligosaccharides: alpha(1-2)-, alpha(1-3)-, beta(1-2)-, and beta(1-4)-linked units

The solution conformation is presented for representatives of each of the major classes of asparaginyl oligosaccharides. In this report the conformation of alpha(1-3)-, alpha(1-2)-, beta(1-2)-, and beta(1-4)-linked units is described. The conformational properties of these glycopeptides were determined by high-resolution 1H nuclear magnetic resonance in conjunction with potential energy calculations. The NMR parameters that were used in this analysis were chemical shifts and nuclear Overhauser enhancements. Potential energy calculations were used to evaluate the preferred conformers available for the different linkages in glycopeptides and to draw conclusions about the behavior in solution of these molecules. It was found that the linkage conformation of the Man alpha 1-3 residues was not affected by substitution either at the 2-position by alpha Man or beta GlcNAc or at the 4-position by beta GlcNAc or by the presence of a bisecting GlcNAc on the adjacent beta Man residue.     

基质金属蛋白酶-2、-9及其组织抑制因子(TIMPs)在动情周期大鼠子宫中的表达(英文)

基质金属蛋白酶（ＭＭＰｓ）家族的作用是降解所有细胞外基质,其活性受其特异性组织抑制因子（ＴＩＭＰｓ）的抑制。细胞外基质成分的降解与重组在动物生殖生长过程中起重要作用,其变化可以通过ＭＭＰｓ和ＴＩＭＰｓ两者表达水平的变化进行监测。大鼠虽然没有月经形成,但是在其子宫内膜也出现类似灵长类的生殖生物学变化。本文从ＭＭＰｓ和ＴＩＭＰｓ两者的表达水平,对大鼠子宫内膜的这些变化进行了研究。于大鼠动情周期的不同时期,将其处死、取子宫制备酶粗提液和组织切片,采用酶谱法（ｚｙｍｏｙｒａｎｈｎ）和原位杂交方法研究动情周期大鼠子宫中ＭＭＰ－２和－９的活性变化以及ＭＭＰ－２、－９和ＴＩＭＰ－１、－２、－３ｍＲＮＡ的表达。并通过光密度扫描方法对酶谱结果进行半定量分析。所用杂交探针见Ｔａｂｌｅ１。酶谱结果显示：在动情周期大鼠子宫中只检测到６７ｋＤａ的ＭＭＰ－２活性,而没有检测到ＭＭＰ－９的活性（Ｆｉｇ．１）。ＭＭＰ－２的活性在动情前期最高,动情期和动情后期次之,间情期最低（Ｆｉｇ．２）。原位杂交结果显示：ＭＭＰ－２、－９、ＴＩＭＰ－１、－２、－３ｍＲＮＡ主要在子宫内膜基底部的基质细胞中表达。ＭＭＰ－２和－９ｍＲＮＡ在动情前期、动情期和动     

Diastereoisomers of 2-benzyl-2, 3-dihydro-2-(1H-inden-2-yl)-1H-inden-1-ol: Potential anti-inflammatory agents

The synthesis and biological activity of the novel diastereoisomers of 2-benzyl-2,3-dihydro-2-(1H-inden-2-yl)-1H-inden-1-ol is reported. The 2,2-coupled indane dimers were synthesised by coupling of the silyl enol ether of 1-indanone with the dimethyl ketal of 2-indanone. The coupled product was directly alkylated to give the racemic ketone which was reduced to the diastereoisomeric alcohols. The alcohols were separated and their relative stereochemistry was established by X-ray crystallography. These molecules demonstrate significant anti-inflammatory activity in vivo and in vitro and may represent a new class of anti-inflammatory agent.