Age related reactivation of an X-linked gene

We have investigated age-related reactivation of the X chromosome by devising a model in which reactivation of a single gene in one cell among many can be identified. We have used mice with an X-autosomal translocation giving consistent non-random inactivation of the normal X (as judged by biochemical and cytogenetic techniques), that also carry a defective form of a histochemically demonstrable X-linked enzyme. When the gene for the normal enzyme was located on the inactivated normal X a uniformly negative histochemical picture would be predicted in doubly heterozygous animals. A very small proportion of enzyme-positive cells was found in young animals. This proportion increased very significantly with age, but the patch size did not change, showing that the result was not due to preferential division of enzyme-positive cells, but was instead due to the conversion of previously enzyme-negative to enzyme-positive cells. These observations provide the first evidence with a true X-linked gene for an age-related decrease in the stability of the X-inactivation mechanism.     

Telomeres shorten during ageing of human fibroblasts

The terminus of a DNA helix has been called its Achilles' heel. Thus to prevent possible incomplete replication and instability of the termini of linear DNA, eukaryotic chromosomes end in characteristic repetitive DNA sequences within specialized structures called telomeres. In immortal cells, loss of telomeric DNA due to degradation or incomplete replication is apparently balanced by telomere elongation, which may involve de novo synthesis of additional repeats by novel DNA polymerase called telomerase. Such a polymerase has been recently detected in HeLa cells. It has been proposed that the finite doubling capacity of normal mammalian cells is due to a loss of telomeric DNA and eventual deletion of essential sequences. In yeast, the est1 mutation causes gradual loss of telomeric DNA and eventual cell death mimicking senescence in higher eukaryotic cells. Here, we show that the amount and length of telomeric DNA in human fibroblasts does in fact decrease as a function of serial passage during ageing in vitro and possibly in vivo. It is not known whether this loss of DNA has a causal role in senescence.     

The glycoprotein encoded by the X-linked chronic granulomatous disease locus is a component of the neutrophil cytochrome b complex

The bacteriocidal capacity of phagocytic cells is impaired in X-linked chronic granulomatous disease (X-CGD), a disorder characterized by the absence of functional plasma-membrane-associated NADPH oxidase. The components of this oxidase system, their correspondence with specific genetic loci, and the primary protein defect in X-CGD remain incompletely defined. We recently reported cloning of the putative X-CGD gene on the basis of DNA linkage. To identify the predicted protein in vivo, antibodies were raised to a synthetic peptide derived from the complementary DNA sequence and to a fusion protein produced in Escherichia coli. In Western blots antisera detect a neutrophil protein of relative molecular mass in 90,000 (90K) that is absent in X-CGD patients. Antisera also react with the larger component of cytochrome b recently purified from neutrophil plasma membranes as a complex of glycosylated 90K and non-glycosylated 22K polypeptides. Based on our identification of the X-CGD protein in vivo, we propose that one of its critical roles is to interact with the 22K species to form a functional cytochrome b complex.     

高温短时人工时效对2524合金疲劳性能的影响

研究高温短时时效对2524合金室温拉伸及疲劳性能的影响,采用3DAP分析、透射电镜等对合金组织进行观察.结果表明:经过高温短时时效试样的抗拉强度与自然时效试样的相当,但是塑性有很大的提高;高温短时时效后试样的疲劳裂纹扩展速率比自然时效试样低.经过高温短时人工时效的2524合金组织中Cu和Mg原子发生强烈偏聚形成圆盘状的GPB区,尺寸较大,这种人工时效组织既能提高应力循环下的裂纹张开扩展阻力,又不影响裂纹闭合,从而降低疲劳裂纹扩展速率.     

Structure of the human fetal globin gene locus.

We have derived a 'map' of restriction enzyme sites in and around the human gamma-globin genes. This has enabled us to show that there are two gamma-globin genes per haploid set, that the genes contain 'introns' within the same regions of DNA as the human beta and delta-globin genes, and that the genes are 3,500 base pairs apart. We conclude that the correct gene organisation of the human beta-like globin locus is GgammaAgammadeltabeta.     

2519铝合金薄板在不同时效状态的抗晶间腐蚀能力

研究了2519铝合金薄板经165 ℃不同时效状态的晶间腐蚀情况,分析了产生不同腐蚀情况的组织原因.研究结果表明:欠时效状态有明显的晶间腐蚀;而峰值时效或过时效状态无晶间腐蚀敏感性,且样品的峰值时效状态晶间腐蚀比过时效状态严重;欠时效状态下,晶界上具有较宽的无沉淀带,且析出粗大的沉淀相;而峰值时效和过时效状态下无沉淀带很窄,晶界上有较细小且离散均匀分布的第2相粒子;晶间腐蚀是作为阳极的贫铜区发生腐蚀形成溶解通道所致;贫铜区越宽,晶间腐蚀越严重,且其中大的脱溶相也降低了晶界的耐蚀能力.     

Targeted integration of baboon endogenous virus in the BEVI locus on human chromosome 6

The infection of cultured human cells with baboon endogenous virus (BEV) frequently leads to an association of viral DNA with a specific genetic locus (termed BEVI, for baboon endogenous virus infection) on chromosome 6. Restriction endonuclease digestion of DNA from BEV-infected human cells and their derived somatic cell clones frequently revealed a common cellular DNA sequence in the proximity of one of the junctions between cellular DNA and the integrated virus. We propose that a short cellular DNA sequence, repeated on chromosome 6 and separated by unique DNA sequences, presents a high-affinity target for the integration of BEV in human cells.     

时效热处理对HR3C钢组织结构及力学性能的影响

根据Larson-Miller参数法制订HR3C钢热处理工艺,文章研究时效热处理对HR3C钢组织结构和性能的影响.结果表明,供货态HR3C钢奥氏体晶粒较大,组织孪晶特征明显,晶界、晶内弥散分布着细小的M23C6及MX第二相颗粒;经800℃、110.4 h时效处理,M23C6在晶界析出,呈半连续的链状分布,同时,晶内也析...     

Insertion of DNA sequences into the human chromosomal beta-globin locus by homologous recombination

A 'rescuable' plasmid containing globin gene sequences allowing recombination with homologous chromosomal sequences has enabled us to produce, score and clone mammalian cells with the plasmid integrated into the human beta-globin locus. The planned modification was achieved in about one per thousand transformed cells whether or not the target gene was expressed.     

The mapping of a cDNA from the human X-linked Duchenne muscular dystrophy gene to the mouse X chromosome

The recent discovery of sequences at the site of the Duchenne muscular dystrophy (DMD) gene in humans has opened up the possibility of a detailed molecular analysis of the genes in humans and in related mammalian species. Until relatively recently, there was no obvious mouse model of this genetic disease for the development of therapeutic strategies. The identification of a mouse X-linked mutant showing muscular dystrophy, mdx, has provided a candidate mouse genetic homologue to the DMD locus; the relatively mild pathological features of mdx suggest it may have more in common with mutations of the Becker muscular dystrophy type at the same human locus, however. But the close genetic linkage of mdx to G6PD and Hprt on the mouse X chromosome, coupled with its comparatively mild pathology, have suggested that the mdx mutation may instead correspond to Emery Dreifuss muscular dystrophy which itself is closely linked to DNA markers at Xq28-qter in the region of G6PD on the human X chromosome. Using an interspecific mouse domesticus/spretus cross, segregating for a variety of markers on the mouse X chromosome, we have positioned on the mouse X chromosome sequences homologous to a DMD cDNA clone. These sequences map provocatively close to the mdx mutation and unexpectedly distant from sparse fur, spf, the mouse homologue of OTC (ornithine transcarbamylase) which is closely linked to DMD on the human X chromosome.     

A molecular basis for the two locus model of human complement component C4

The major histocompatibility complex(MHC)-linked fourth component of complement (C4) shows a high degree of polymorphism in several animal species. In man C4 polymorphism was detected by distinct charge differences of the variants. O'Neill et al. showed that this C4 polymorphism was controlled by two closely linked genetic loci, F (C4A) and S (C4B) and these results were extended by Awdeh et al. with an improved typing method. Biochemical analysis of human C4 has revealed that it consists of three polypeptide chains, alpha, beta and gamma. In all reports so far on the molecular analysis of human C4, no molecular weight differences between the A and B locus-encoded molecules have been noticed. Here we demonstrate that the C4A and C4B locus-encoded alpha-chains have a molecular weight (MW) of 96,000 and 94,000, respectively, presenting for the first time a molecular basis for the difference between all C4A and C4B variants tested. Even rare variants that are difficult to allocate to the A or B locus on the basis of charge differences could be identified as C4A or C4B variants in this way, thereby providing new insights into the relationships between the C4A and C4B loci.