Nucleotide sequence of epidermal growth factor cDNA predicts a 128,000-molecular weight protein precursor

Epidermal growth factor (EGF) has a profound effect on the differentiation of specific cells in vivo, and has been shown to be a potent mitogenic factor for a variety of cultured cells, of both ectodermal and mesodermal origin (see ref. 1 for review). This 53-amino acid polypeptide of known sequence contains six cysteine residues, which are thought to form three intrachain disulphide bonds. Urogastrone, a polypeptide bearing anti-gastric secretory activity isolated from human urine, which is presumably synthesized in submandibular and Brunner's glands, shares extensive sequence homology (70%) with EGF and may represent the human EGF equivalent. Here we present the sequence of a mouse EGF cDNA clone, which suggests that EGF is synthesized as a large protein precursor of 1,168 amino acids. Our data indicate that the discrepancy between EGF levels in male and female mouse submaxillary glands (MSGs) is due to different EGF mRNA levels in these tissues, and suggest that precursor EGF processing may differ from that described previously for other polypeptide hormones.     

Molecular analysis of spontaneous somatic mutants.

Eukaryotic structural gene mutations occurring spontaneously in a mouse myeloma cell line offer the opportunity to study somatic mutation in animal cells at the molecular level. Studies on the myeloma protein and on mRNA have enabled us to characterise four such mutants representing four different mutation mechanisms. The results may have some bearing on the origin of antibody diversity.     

The Xenopus localized messenger RNA An3 may encode an ATP-dependent RNA helicase

The maternal messenger RNA An3 was originally identified localized to the animal hemisphere of Xenopus laevis oocytes, eggs and early embryos. Xenopus embryos depend on mRNA and protein present in the egg before fertilization (maternal molecules) to provide the information needed for early development. Localization of maternal mRNA gives cells derived from different regions of the egg distinctive capacities for protein synthesis. We show here that An3 mRNA encodes a protein with 74% identity to a protein encoded by the testes-specific mRNA PL10 found in mouse, which is proposed to have RNA helicase activity. Because the gene encoding An3 mRNA is reactivated after gastrulation and remains active throughout embryogenesis, we have examined its distribution in embryonic and adult tissues. Unlike PL10 mRNA, which is primarily restricted to the testes, An3 mRNA is broadly distributed in later development.     

Reversible inhibition of translation by Xenopus oocyte-specific proteins

A characteristic of growing oocytes of all animal species is the synthesis and accumulation of messenger RNA which is destined to be used primarily by the early embryo. The mechanism(s) which regulates the translation of this maternal mRNA remains unknown. However, the inability of the oocyte to translate all of its putative mRNA has been attributed to at least three limitations: (1) The rate of translation is limited by the availability of components of the translational apparatus other than mRNA, (2) the structural organization of the mRNA prevents translation, and (3) proteins associated with the mRNA prevent translation. Several investigators have suggested that proteins associated with maternal mRNA suppress translation in sea urchin eggs, although others claim that such results may be due to experimental artefacts. Oocyte-specific proteins have been identified in association with non-translating poly(A)+ mRNAs from Xenopus laevis oocytes, and we report here that when these proteins are reconstituted with mRNAs in vitro the translation of the mRNAs in vitro is reversibly repressed. The implication is that these proteins are involved in the regulation of translation of stored maternal mRNAs.     

Sequence-induced DNA curvature at the bacteriophage lambda origin of replication

DNA replication in bacteriophage lambda begins at a unique origin between residues 39,000 and 39,200 of the lambda genome. This segment of DNA serves a dual function since it also lies within the coding sequence of the lambda replication initiator protein O which binds origin DNA. The lambda origin sequence contains four 19-base-pair (bp) segments (iterons) which have dyad symmetry, followed by a 40-bp A + T-rich zone of highly asymmetrical base composition. It was noted earlier that lambda origin DNA exhibits an anomalous electrophoretic mobility on gels; that is, the length of DNA as determined by DNA sequencing is approximately 20% less than is predicted from electrophoretic mobility. Recent studies of kinetoplast minicircle DNA (K-DNA) from the protozoan Leishmania tarentolae have led to the proposal that sequence-induced DNA curvature could account for such electrophoretic anomalies by alteration of the shape of the DNA molecule. We now present evidence that the lambda origin contains a static curve.     

一类三次幂零奇点的中心焦点判定与极限环分支

研究了一类原点为三次幂零奇点的三次微分系统.对一类三次系统给出了计算原点拟Lyapunov常数的递推公式,并在计算机上用Mathematics推导出该系统原点的前6个拟Lyapunov常数,进而推导出原点成为中心和最高阶细焦点的条件,并在此基础上得到了对系统作适当的微小扰动时,在原点充分小的邻域内恰有6个包围原点的极限环的结论.     

Origin of a gene regulatory mechanism in the evolution of echinoderms

A rich diversity of ancient sea urchin lineages survives to the present. These include several advanced orders as well as the cidaroids, which represent the group ancestral to all other sea urchins. Here we show that all advanced groups of sea urchins examined possess in their eggs a class of maternal messenger RNA (mRNA) encoded by the evolutionarily highly conserved alpha-subtype histone genes. The maternal histone mRNAs are unique in their time of accumulation in oogenesis, their localization in the egg nucleus and their delayed timing of translation after fertilization. Cidaroid sea urchins as well as other echinoderm classes, such as starfish and sea cucumbers, possess the genes but do not have maternal alpha-subtype histone mRNAs in their eggs. Thus, although all the echinoderms examined transcribe alpha-subtype histone genes during embryogenesis, the expression of these genes as maternal mRNAs is confined to advanced sea urchins. The fossil record allows us to pinpoint the evolution of this mode of expression of alpha-histone genes to the time of the splitting of advanced sea urchin lineages from the ancestral cidaroids in a radiation which occurred in a relatively brief interval of time approximately 190-200 Myr ago. The origin of a unique gene regulatory mechanism can thus be correlated with a set of macroevolutionary events.     

论文章哲学

本文运用哲学观点反思文章及其起源、生成、系统、信息、控制、价值、道德诸问题,认为文章文学的两分法具有合理性,是一分为二和一分为三的辩证统一;指出文章的始源实在是文字语言,分析了关于文章起源的纷争;论述了文章生成及何以生成,剖析了文章生成及其原因的各种猜测;首次对文章系统、文章信息、文章控制的运动过程进行了阐释;文章价值评价是主客观统一的具体分析有自己的见解;文章道德建设的建议具有一定的现实意义.     

一类拟三次系统的中心条件与极限环分支

研究了一类拟三次系统的奇点量、中心焦点判定与极限环分支问题,首先通过适当的变换将系统的原点(无穷远点)转化为原点,得到了系统原点的前21个奇点量,从而导出原点为中心和最高阶细焦点(细奇点)的条件,并分别给出了原点和无穷远点分支出4个极限环的实例.     

Orientation of DNA replication establishes mating-type switching pattern in S. pombe.

The fission yeast Schizosaccharomyces pombe normally has haploid cells of two mating types, which differ at the chromosomal locus mat1. After two consecutive asymmetric cell divisions, only one in four 'grand-daughter' cells undergoes a 'mating-type switch', in which genetic information is transferred to mat1 from the mat2-P or mat3-M donor loci. This switching pattern probably results from an imprinting event at mat1 that marks one sister chromatid in a strand-specific manner, and is related to a site-specific, double-stranded DNA break at mat1. Here we show that the genetic imprint is a strand-specific, alkali-labile DNA modification at mat1. The DNA break is an artefact, created from the imprint during DNA purification. We also propose and test the model that mat1 is preferentially replicated by a centromere-distal origin(s), so that the strand-specific imprint occurs only during lagging-strand synthesis. Altering the origin of replication, by inverting mat1 or introducing an origin of replication, affects the imprinting and switching efficiencies in predicted ways. Two-dimensional gel analysis confirmed that mat1 is preferentially replicated by a centromere-distal origin(s). Thus, the DNA replication machinery may confer different developmental potential to sister cells.     

Splicing factor Sub2p is required for nuclear mRNA export through its interaction with Yra1p.

The yeast nuclear protein Yra1p is an essential export factor for mRNA. Yra1p interacts directly with the mRNA transport factor Mex67p/Mtr2p, which is associated with the nuclear pore. Here, we report a genetic interaction between YRA1 and SUB2, the gene for a DEAD box helicase involved in splicing. Mutation of SUB2 as well as its overexpression leads to a defect in mRNA export. Moreover, Yra1p and Sub2p bind directly to each other both in vivo and in vitro. Significantly, Sub2p and Mex67p/Mtr2p bind to the same domains of Yra1p, and the proteins compete for binding to Yra1p. Together, these data indicate that the spliceosomal component Sub2p is also important in mRNA export and may function to recruit Yra1p to the mRNA. Sub2p may then be displaced from Yra1p by the binding of Mex67p/Mtr2p, which participates in the export of mRNA through the nuclear pores.     

宇宙演化总论——二十一世纪广义宇宙学新探索(上)

从广义宇宙学的视角论述了物质起源、宇宙起源、生命与智慧起源等宇宙演化的总体过程,指出宇宙由信息宇宙和物质宇宙共同组成,两者处于无限交流循环的进化状态.针对现代宇宙学研究的一系列焦点问题,诸如黑洞及大爆炸奇点、宇宙对称破缺、引力形态、暗物质、暗能量、类星体能量等进行了溯本求源的剖析;对信息宇宙和物质宇宙的关系、构成宇宙万物的最小基础粒子--单奇子的信息及物质两态性、溢散态正引力空间等宁宙构成的原初问题进行了论述.希望本文创立的广义宇宙学能成为后世宇宙学研究的阶梯.     

miRNA调控诱导的随机增益和双峰表达

一方面,miRNA通过加速mRNA的降解对基因表达进行后转录调控; 另一方面,最新的研究表明某些细胞中miRNA以切换的方式对mRNA进行调控.基于此,建立起一个miRNA后转录调控的基因表达模型.通过对相应化学主方程的分析求解与数值模拟,研究了miRNA调控过程中的噪声对mRNA表达的定量和定性影响.结果显示:这种随机涨落既能提高mRNA的平均表达水平(称这种现象为随机增益)又能诱导mRNA的双峰表达.研究结果表明:miRNA后转录调控是一种有效控制基因表达的机制.     

谷胱甘肽硫转移酶在东亚飞蝗两个种群mRNA的表达研究

为研究东亚飞蝗谷胱甘肽硫转移酶基因(GSTs)表达与代谢能力的相关性,应用实时荧光定量PCR技术,对东亚飞蝗沧州和天津种群9个谷胱甘肽硫转移酶基因的mRNA表达情况进行了研究.结果表明:9个GSTs基因在东亚飞蝗不同发育阶段具有表达差异,基因LmGST1、LmGST3、LmGST5、LmGST7和LmGST8随着蝗虫的生长发育表达量增高,这些基因可能影响虫体对有毒化学物质的敏感性.沧州种群GSTs的表达水平高于天津种群,据此推测沧州种群个体对有机磷农药的代谢解毒能力强,对杀虫剂的敏感性低.     

Nucleotide sequence of cloned cDNA of human c-myc oncogene

Like other transforming genes of retroviruses, the v-myc gene of the avian virus, MC29, has a homologue in the genome of normal eukaryotic cells. The human cellular homologue, c-myc, located on human chromosome 8, region q24 leads to qter (refs 1, 2), is translocated into the immunoglobulin heavy-chain locus on human chromosome 14 (ref. 3) in Burkitt's lymphoma, suggesting that c-myc has a primary role in transformation of some human haematopoietic cells. In addition, c-myc is amplified in the human promyelocytic leukaemia cell line, HL60 (refs 6, 7) which also contains high levels of c-myc mRNA. Recently, Colby et al. reported the nucleotide sequence of the human c-myc DNA isolated from a genomic recombinant DNA library derived from human fetal liver. This 4,053-base pair (bp) sequence includes two exons and one intron of the myc gene, and the authors have suggested the existence of a human c-myc mRNA of 2,291 nucleotides that has a coding capacity for a protein of molecular weight (Mr) 48,812. We have approached the problem of accurately defining the characteristics of the human c-myc mRNA and c-myc protein by determining the sequence of the c-myc cDNA isolated from a cDNA library prepared from mRNA of a clone of the K562 human leukaemic cell line. K562 cells are known to contain c-myc mRNA which is similar in size to the c-myc mRNA of other human cell types. We report here the sequence of 2,121 nucleotides of a human c-myc mRNA and demonstrate that its 5' noncoding sequence does not correspond to the sequence of the reported genomic human sequence. However, our data confirm that the intact human c-myc mRNA can encode a 48,812-Mr protein with a sequence identical to that reported by Colby et al.     

Pre-mRNA splicing and mRNA export linked by direct interactions between UAP56 and Aly.

Recent studies indicate that splicing of pre-messenger RNA and export of mRNA are normally coupled in vivo. During splicing, the conserved mRNA export factor Aly is recruited to the spliced mRNA-protein complex (mRNP), which targets the mRNA for export. At present, it is not known how Aly is recruited to the spliced mRNP. Here we show that the conserved DEAD-box helicase UAP56, which functions during spliceosome assembly, interacts directly and highly specifically with Aly. Moreover, UAP56 is present together with Aly in the spliced mRNP. Significantly, excess UAP56 is a potent dominant negative inhibitor of mRNA export. Excess UAP56 also inhibits the recruitment of Aly to the spliced mRNP. Furthermore, a mutation in Aly that blocks its interaction with UAP56 prevents recruitment of Aly to the spliced mRNP. These data suggest that the splicing factor UAP56 functions in coupling the splicing and export machineries by recruiting Aly to the spliced mRNP.     

多项式广义Lienard方程的细奇点与可积性

本文在作者原有工作的基础上，讨论多项式文广义Ｌｉｅｎａｒｄ系统。首先，研究该系统在原点领域存在正则积分的充分必要条件，接着给出原点能作为该系统的精细度为Ｋ阶的临界型细奇点的条件，对于系统存在多个奇点的情形，估计了全体临界型细奇点业精细度之和的上界，并研究了全部初等奇点的整体性质。