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41.
Anne?W.?Higgins Karen?M.?Gustashaw Huntington?F.?WillardEmail author 《Chromosome research》2005,13(8):745-762
The centromere is essential for the faithful distribution of a cell's genetic material to subsequent generations. Despite
intense scrutiny, the precise genetic and epigenetic basis for centromere function is still unknown. Here, we have used engineered
dicentric human chromosomes to investigate mammalian centromere structure and function. We describe three classes of dicentric
chromosomes isolated in different cell lines: functionally monocentric chromosomes, in which one of the two genetically identical
centromeres is consistently inactivated; functionally dicentric chromosomes, in which both centromeres are consistently active;
and dicentric chromosomes heterogeneous with respect to centromere activity. A study of serial single cell clones from heterogeneous
cell lines revealed that while centromere activity is usually clonal, the centromere state (i.e. functionally monocentric
or dicentric) in some lines can switch within a growing population of cells. Because pulsed field gel analysis indicated that
the DNA at the centromeres of these chromosomes did not change detectably, this switching of the centromere state is most
likely due to epigenetic changes. Inactivation of one of the two active centromeres in a functionally dicentric chromosome
was observed in a percentage of cells after treatment with Trichostatin A, an inhibitor of histone deacetylation. This study
provides evidence that the activity of human centromeres, while largely stable, can be subject to dynamic change, most likely
due to epigenetic modification. 相似文献
42.
本文观察了体外丙二醛(MDA),铜离子(Cu2+氧化修饰的脂蛋白(a)[Lp(a)]结构和生物学性质的变化。氧化修饰Lp(a)过氧化程度增高,负电荷增加,易被巨噬细胞—清道夫受体识别和摄取。MDA修饰Lp(a)出现新的MDA-LDL位点;同纤维蛋白溶酶原(Pg)竞争抑制试验显示氧化、修饰Lp(a)同Pg同源性增加。提示载脂蛋白(a)状态同动脉粥样硬化的病理过程有关。 相似文献
43.
Post-translational modifications of conserved N-terminal tail residues in histones regulate many aspects of chromosome activity. Thr 3 of histone H3 is highly conserved, but the significance of its phosphorylation is unclear, and the identity of the corresponding kinase unknown. Immunostaining with phospho-specific antibodies in mammalian cells reveals mitotic phosphorylation of H3 Thr 3 in prophase and its dephosphorylation during anaphase. Furthermore we find that haspin, a member of a distinctive group of protein kinases present in diverse eukaryotes, phosphorylates H3 at Thr 3 in vitro. Importantly, depletion of haspin by RNA interference reveals that this kinase is required for H3 Thr 3 phosphorylation in mitotic cells. In addition to its chromosomal association, haspin is found at the centrosomes and spindle during mitosis. Haspin RNA interference causes misalignment of metaphase chromosomes, and overexpression delays progression through early mitosis. This work reveals a new kinase involved in composing the histone code and adds haspin to the select group of kinases that integrate regulation of chromosome and spindle function during mitosis and meiosis. 相似文献
44.
New Zealand white rabbits immunized with RNA-complexed total histones develop an autoimmune-like response.
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C Atanassov J P Briand D Bonnier M H Van Regenmortel S Muller 《Clinical and experimental immunology》1991,86(1):124-133
The antibody response of rabbits immunized with a total histone mixture containing randomly coiled H1/H5, H2A, H2B, H3 and H4 devoid of DNA was investigated in direct and competitive ELISA. The antisera were tested with isolated histones and chromatin and with a series of overlapping synthetic peptides covering the entire sequences of the four core histones and two peptides of H1. It was found that the New Zealand (NZ) white rabbits immunized with the total histone (TH) mixture complexed with RNA produced IgG antibodies reacting with histones and with a number of histone peptides but not with chromatin. The antisera also contained IgG antibodies which bound components that correspond to common target antigens in autoimmune diseases such as native dsDNA, peptides of Sm-D antigen, ubiquitin, branched peptides of ubiquitinated H2A and poly(ADP-ribose). By competition experiments, it was shown that these antibodies corresponded to non-crossreacting antibody populations. New Zealand rabbits immunized with TH in the absence of RNA or random outbred rabbits immunized with the RNA-complexed histone fraction produced antibodies reacting with histone, chromatin and very few histone peptides, while no activity with non-related antigens was observed. The pattern of reactivity of antisera raised in NZ rabbits with RNA-complexed TH was found to be very similar to that observed in sera of patients with systemic lupus erythematosus while, in contrast, the antibody response was very different in NZ or outbred rabbits immunized with various native nuclear particles and with individual histones. Altered nucleosome particles rather than native nucleosomes may represent the antigenic stimulus giving rise to autoantibodies. 相似文献
45.
Smith KR 《International journal of medical sciences》2004,1(2):76-91
The theoretical possibility of applying gene transfer methodologies to the human germline is explored. Transgenic methods for genetically manipulating embryos may in principle be applied to humans. In particular, microinjection of retroviral vector appears to hold the greatest promise, with transgenic primates already obtained from this approach. Sperm-mediated gene transfer offers potentially the easiest route to the human germline, however the requisite methodology is presently underdeveloped. Nuclear transfer (cloning) offers an alternative approach to germline genetic modification, however there are major health concerns associated with current nuclear transfer methods. It is concluded that human germline gene therapy remains for all practical purposes a future possibility that must await significant and important advances in gene transfer technology. 相似文献
46.
47.
Summary Specific exclusion relations are know among the three Ustilago maydis viruses that are associated with the cytoplasmically transmitted killer phemomenon. Of the three viruses P1, P4 and P6, only P1, and P4 cancoexist in one host cell. Mutual exclusion occurs between P1 and P6 and P4 unilaterally excludes P6. The exclusion relations were originally defined among the wild-type viruses. Those relations can be modified by two specific segments that are a part of the P4 dsRNA genome and were also found in some sensitive strains that contained part of the viral genome. Also, deletion of the dsRNA segment that is assumed to encode the toxin information permits the formation of hybrid genomes that otherwise cannot be formed. The data is interpreted in terms of a dsRNA restriction modification system in which the killer toxin or a toxin-linked function acts as the restriction factor and segments H3 and H4 or H4 alone contain the necessary information for the modification of certain sites on the M and L segments of the P1 and P4 viruses but not on the P6 segments. 相似文献
48.
Kazutoshi Kudo T. Ohtsuki 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1998,122(1):23-30
Subjects made a fast elbow extension movement to designated target in response to a go signal. In 45% of trials a stop signal
was presented after the go signal, to which subjects were asked to stop the movement as rapidly as possible. The interstimulus
interval (ISI), or time interval between the go and stop signals, was randomly varied between 0 and 200 ms. Electromyographic
(EMG) activity was recorded from biceps brachii and triceps brachii. Subjects could sometimes completely inhibit initiation
of the movements when the ISI was 0 ms, but could rarely do so when the ISI exceeded 100 ms. For responses that were initiated
but stopped on the way, the amplitude of the movement decreased linearly as the time interval (=modification time) from the
stop signal to EMG onset increased. The peak velocity increased linearly as the movement amplitude increased. This tendency
was similar to those previously reported in step-tracking movements with various amplitudes. In spite of the similarity in
the kinematics of the movement, the EMG pattern was different from that of step-tracking movement. While the initial agonist
burst (AG1) decreased linearly after the modification time exceeded 100 ms, the antagonist burst (ANT) increased compared
with the go trial for the modification time from 0 to 200 ms and decreased after the modification time exceeded 300 ms. This
change of activation is analogous to functional modification of middle-latency reflex EMG response to load, or cutaneous perturbation.
In conclusion, it is suggested that adaptive mechanisms, which would functionally modify the reflex responses, are also continuously
working during voluntary movements in response to sudden changes in environmental information.
Received: 3 November 1997 / Accepted: 3 February 1998 相似文献
49.
A protein, Vp130, that interacts with the host cell wall was isolated from Chlorovirus CVK2. From its peptide sequence, the gene for Vp130 was identified on the PBCV-1 genomic sequence as an ORF combining A140R and A145R. In Vp130, the N-terminus was somehow modified and the C-terminus was occupied by 23-26 tandem repeats of a PAPK motif. In the internal region, Vp130 contained seven repeats of 70-73 amino acids, each copy of which was separated by PAPK sequences. This protein was well conserved among NC64A viruses. A recombinant rVp130N protein formed in Escherichia coli was shown not only to bind directly to the host cell wall in vitro but also to specifically bind to the host cells, as demonstrated by fluorescence microscopy. Because externally added rVp130N competed with CVK2 to bind to host cells, Vp130 is most likely to be a host-recognizing protein on the virion. 相似文献
50.
《Immunity》2019,50(5):1289-1304.e6
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