The mechanism of Z alpha 1-antitrypsin accumulation in the liver.

Most northern Europeans have only the normal M form of the plasma protease inhibitor alpha 1-antitrypsin, but some 4% are heterozygotes for the Z deficiency variant. For reasons that have not been well-understood, the Z mutation results in a blockage in the final stage of processing of antitrypsin in the liver such that in the Z homozygote only 15% of the protein is secreted into the plasma. The 85% of the alpha 1-antitrypsin that is not secreted accumulates in the endoplasmic reticulum of the hepatocyte; much of it is degraded but the remainder aggregates to form insoluble intracellular inclusions. These inclusions are associated with hepatocellular damage, and 10% of newborn Z homozygotes develop liver disease which often leads to a fatal childhood cirrhosis. Here we demonstrate the molecular pathology underlying this accumulation and describe how the Z mutation in antitrypsin results in a unique molecular interaction between the reactive centre loop of one molecule and the gap in the A-sheet of another. This loop-sheet polymerization of Z antitrypsin occurs spontaneously at 37 degrees C and is completely blocked by the insertion of a specific peptide into the A-sheet of the antitrypsin molecule. Z antitrypsin polymerized in vitro has identical properties and ultrastructure to the inclusions isolated from hepatocytes of a Z homozygote. The concentration and temperature dependence of this loop-sheet polymerization has implications for the management of the liver disease of the newborn Z homozygote.     

分圆域Q(ζ15)的幂元整基

称一个伽罗华数域L有一个幂元整基,如果它的代数整数环具有形式Z[α],其中α∈L.并且此时称α为幂元整基的生成元.两个幂元整基的生成元α和α′称为等价的,如果α′=m±σ(α),其中m∈Z并且σ∈Gal(L/Q).讨论了分圆域Q(ζ15)的幂元整基的生成元,其中ζ15是15次本原单位根.众所周知ζ15,(1-ζ15)-1和(1 ζ15)-1都是分圆域Q(ζ15)的幂元整基的生成元.证明了当α α-Z时α是分圆域Q(ζ)的幂元整基的生成元当且仅当α与ζ等价.     

Analysis of gain-of-function mutations of the lin-12 gene of Caenorhabditis elegans

Certain cell fate decisions are specified by cell-cell interactions during the development of the nematode Caenorhabditis elegans. For example, in a wild-type hermaphrodite gonad, two cells, Z1.ppp and Z4.aaa, have the potential to become the anchor cell (AC). Intercellular communication establishes their fates and ensures that only one cell becomes the AC, while the other becomes a ventral uterine precursor cell (VU). One component of this intercellular communication seems to be the 'AC-to-VU' signal from the presumptive AC that causes the other cell to become a VU. Genetic and developmental studies indicated that the lin-12 gene specifies the fates of Z1.ppp and Z4.aaa. Molecular studies suggest that lin-12 directly participates in their communications, perhaps acting as the receptor for the 'AC-to-VU' signal. Here, we report the molecular lesions associated with lin-12 gain-of-function mutations, cell isolation experiments, and genetic studies of an unusual lin-12 allele. These data suggest that self-association of the putative lin-12-encoded receptor leads to its activation, and that certain gain-of-function mutations result in ligand-independent activation.     

高纯多晶铝的动态再结晶

将99.992%高纯多晶铝在533～773 K时以0.002～2.000 s-1的应变速率压缩到其真应变为0.92.采用真应力-真应变曲线以及偏光金相和透射电镜研究高纯铝高温塑性变形特征,研究了形变条件对高纯铝动态软化机制的影响.研究结果表明:高纯铝的动态软化机制与Zenner- Hollomon参数Z密切相关,当Z较大时,试样仅发生动态回复;Z处于中间值时,发生连续动态再结晶;Z较小时,发生不连续动态再结晶,但真应力-真应变曲线未出现波动.     

A point mutation in the A gamma-globin gene promoter in Greek hereditary persistence of fetal haemoglobin

Hereditary persistance of fetal haemoglobin (HPFH) is a benign condition characterized by the production in adulthood of more than 1% fetal haemoglobin (HbF, alpha 2 gamma 2) in the absence of erythropoietic stress. Several genetic types have been discerned based on the level of HbF produced, the relative contributions of the duplicated fetal (G gamma and A gamma) globin genes, and the presence or absence of deletions involving the beta and delta genes in cis to the mutation. Greek HPFH is a non-deletion variety in which heterozygotes produce 10-20% HbF, predominantly due to overproduction of the A gamma chain. We have cloned a 40-kilobase (kb) region of the beta-globin cluster from a Greek HPFH allele and report here that a point mutation (G----A) occurs 117 base pairs (bp) 5' to the cap site of the A gamma-globin gene, just upstream of the distal CCAAT sequence. The corresponding region of the G gamma-globin gene is normal. We discuss the implications of this finding for the developmental regulation of globin gene expression.     

牛角藓 Cratoneuron filicinum（Hedw.）Spruce多样性的 SRAP 标记研究

利用SRAP分子标记方法对不同地区的13份牛角藓 Cratoneuron f ilicinum（Hedw ．） Spruce样本进行遗传多样性分析．结果表明,稳定且重复性高的15对引物共扩增出162条清晰的条带,其中161条具有多态性,平均多态性位点比率为99．49％,说明牛角藓的遗传变异丰富．运用PopGen-32软件分析发现,平均等位基因数 Na＝1．9938,有效等位基因数 Ne＝1．6248,Nei＇s基因多样性指数 H＝0．3606,Shannon＇s信息指数 I＝0.5366,遗传分化系数Gst为0．5736,说明牛角藓的遗传变异主要在居群之间．通过NTSYS2．1软件对14份样本的亲缘关系用U PG-M A方法进行聚类,样本的遗传距离与地理位置没有相关性．     

苯乙炔封端含萘环的聚酰亚胺树脂

将二胺单体1,3 双（4 氨基苯氧基）苯（1,3,4-APB）、3,4 二氨基二苯醚（3,4-ODA）分别与3,3′,4,4′-联苯四酸二酐（s-BPDA）和1,4,5,8 萘四甲酸二酐（NTDA）进行缩聚反应，并在两种不同合成条件下合成三种苯乙炔苯酐（PEPA）封端的聚酰亚胺低聚（PI1、PI2、PI3）。结果表明，含六元酸酐环的NTDA与二胺反应不仅形成酰亚胺结构，而且还形成异酰亚胺结构，并且酸性条件下更有利于酰亚胺结构的形成。这三种以苯乙炔苯酐封端的低聚物均具有良好的加工性能和热性能，有很宽的加工窗口，5%热失重温度均5300℃以上。萘环的引入使低聚物固化前后的玻璃化转变温度均有所提高，但也使得低聚物黏度上升。     

A survey of human leukaemias for sequences of a human retrovirus

Human T-cell leukaemia-lymphoma virus (HTLV) is an exogenous human retrovirus distinct from all known animal retroviruses. HTLV is closely linked to a subtype of adult T-cell malignancies and except for isolated cases, has not been found associated with any other form of leukaemia, lymphoma or other cancers (see refs 1, 2 for review). HTLV can be transmitted to cord blood T lymphocytes in vitro and the infected cells exhibit characteristics of transformed neoplastic T cells. We have recently cloned DNA sequences derived from approximately 1 kilobase (kb) of the 5' and 3' termini of the HTLV genome, as well as a 4-5-kb defective HTLV provirus flanked by cellular sequences. The availability of these probes has enabled us to carry out a limited survey of different fresh or cultured cells from patients of different lymphoid and myeloid malignancies for HTLV-related DNA sequences. The results presented here show that cells from all Japanese patients with adult T-cell leukaemia and several patients with various mature T-cell malignancies from elsewhere contained one or more copies of a highly conserved HTLV genome. The infected cells are of clonal origin. Fresh cells from 1 of the 10 myeloid leukaemic patients contained exogenous DNA sequences distantly related to HTLV.     

Internal sequences that distinguish yeast from metazoan U2 snRNA are unnecessary for pre-mRNA splicing

U2 small nuclear RNA is a highly conserved component of the eukaryotic cell nucleus involved in splicing messenger RNA precursors. In the yeast Saccharomyces cerevisiae, U2 RNA interacts with the intron by RNA-RNA pairing between the conserved branchpoint sequence UACUAAC and conserved nucleotides near the 5' end of U2 (ref. 4). Metazoan U2 RNA is less than 200 nucleotides in length, but yeast U2 RNA is 1,175 nucleotides long. The 5' 110 nucleotides of yeast U2 are homologous to the 5' 100 nucleotides of metazoan U2 (ref. 6), and the very 3' end of yeast U2 bears a weak structural resemblance to features near the 3' end of metazoan U2. Internal sequences of yeast U2 share primary sequence homology with metazoan U4, U5 and U6 small nuclear RNA (ref. 6), and have regions of complementarity with yeast U1 (ref. 7). We have investigated the importance of the internal U2 sequences by their deletion. Yeast cells carrying a U2 allele lacking 958 nucleotides of internal U2 sequence produce a U2 small nuclear RNA similar in size to that found in other organisms. Cells carrying only the U2 deletion grow normally, have normal levels of spliced mRNA and do not accumulate unspliced precursor mRNA. We conclude that the internal sequences of yeast U2 carry no essential function. The extra RNA may have a non-essential function in efficient ribonucleoprotein assembly or RNA stability. Variation in amount of RNA in homologous structural RNAs has precedence in ribosomal RNA and RNaseP.     

Extreme value distributions of mixing two sequences with different MDA＇s

Suppose [Xi, i> or =1] and [Yi, i> or =1] are two independent sequences with distribution functions FX(x) and FY(x), respectively. Z(i,n) is the combination of Xi and Yi with a probability pn for each i with 1< or =i< or =n. The extreme value distribution GZ(x) of this particular triangular array of the i.i.d. random variables Z(1,n), Z(2,n),..., Z(n,n) is discussed. We found a new form of the extreme value distribution LambdaA(Rhox)Lambda(x)(0相似文献   

Mutation in the porcine SERPINA7 gene and its association with boar fertility

The porcine SERPINA7 gene is considered as a positional candidate gene responsible for testis size for its location on X chromosome and its biologically critical role in the development of testis. A nonsynonymous polymorphism (His226Asn or C678A) in the ligand-binding domain of SERPINA7 has been identified, which alters SERPINA7’s affinity to thyroxine and is closely associated with testis size. In this study, a primer mutagenesis strategy was developed to genotype this polymorphism in Chinese indigenous pigs and some western commercial pigs. The C allele existed in all tested Chinese indigenous and wild pigs, while the A allele is specific for western commercial breeds, indicating the occurrence of the mutation is of western origin. The correlation of this polymorphism with different boar fertility traits was assessed using a White Duroc × Erhualian intercross which included 110 F₂ mature boars. The results showed that the C678A polymorphism was closely associated with testis weight and epididymis weight (P＜0.0001 and P=0.0016, respectively) with significant heavier testis weight and epididymis weight in boars carrying the A allele than boars with the C allele. A significant correlation was also observed between this polymorphism and total sperm in the ejaculate (P＜0.01) as well as semen volume (P＜0.05). No statistically significant association of the C678A polymorphism with sperm concentration and sperm motility was found.     

Extreme value distributions of mixing two sequences with the same MDA

Suppose [(i), i>or=1] and [Y(i), i>or=1] are two independent sequences with distribution functions F(X)(x) and F(Y)(x), respectively. Z(i,n) is the combination of X(i) and Y(i) with a probability p(n) for each i with 1相似文献   

High-affinity binding site for a specific nuclear protein in the human IgM gene

Proteins binding to specific regions of DNA with high affinity frequently govern or regulate reactions at the gene level. We have identified a high-affinity binding site in the immunoglobulin mu gene that binds a specific nuclear protein, and have now characterized it fully using nuclear factor 1 (NF-1), a protein purified from the nuclei of HeLa cells and required for the in vitro replication of adenovirus (Ad) DNA. NF-1 protects a 25-base pair (bp) double-stranded segment of DNA which shares a consensus sequence, 5' TGGA/CNNNNNGCCAA 3', with similar binding sites in the Ad-5 terminal repeat and the human c-myc gene. Although this site differs from the enhancer region, a biological function is suggested by the fact that it is DNase I hypersensitive in immunoglobulin-producing lymphoblastoid cells. The binding site for the NF-1 protein in the mu gene, by analogy with the site in the Ad-5 terminal repeat, may represent one component of a cellular origin of replication; alternatively, it may be responsible for the activation of the chromatin in this region.     

中国人重症肌无力的遗传易感性研究

重症肌无力与ＨＬＡⅡ类基因关联性在不同人种和民族中具有不同遗传易感性。为探讨中国人重症肌无力（ＭＧ）与ＨＬＡ－ＤＱ分子关联性，采用聚合酶链式反应—限制性片段长度多态性（ＰＣＲ－ＲＦＬＰ）方法，分析了５０例中国正常人及４９例重症肌无力患者的ＨＬＡ－ＤＱＡ１和－ＤＱＢ１座位的基因型。结果：共检出正常人ＤＱＡ１等位基因８种，ＤＱＢ１等位基因１０种，重症肌无力患者ＤＱＡ１等位基因８种，ＤＱＢ１等位基因９种。结果分析表明ＤＱＡ１＊０５０１与ＭＧ成负相关，ＤＱＢ１＊０３０２与ＭＧ成正相关。从基因水平首次用ＰＣＲ－ＲＦＬＰ方法得出中国人重症肌无力ＤＱ分子的易感基因型。     

PI3K-Akt和JNK信号通路抑制剂对杆状病毒诱导昆虫细胞凋亡影响的初步研究

为了探讨杆状病毒诱导昆虫细胞凋亡通路与细胞内PI3K-Akt和JNK信号通路的关系,应用PI3K的特异性抑制剂Wortmannin和JNK的特异性抑制剂SP600125处理芹菜夜蛾核型多角体病毒(AfMNPV)感染的斜纹夜蛾SL-1细胞,研究了这些抑制剂对杆状病毒诱导昆虫细胞凋亡的影响.分别使用浓度梯度2.5,25,50μmol的SP600125和0.3,3,30μmol的Wortmannin处理感染了SfaMNPV的SL-1细胞,24h后进光镜观察、DAPI荧光染色,流式细胞术分析显示,抑制PI3K-Akt和JNK信号通路后杆状病毒诱导的细胞凋亡受到明显影响,细胞凋亡水平明显降低.研究结果提示AfMNPV诱导斜纹夜蛾SL-1细胞凋亡过程可能涉及细胞PI3K-Akt和JNK信号通路.