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101.
Although the product of the UL12 gene of herpes simplex virus type 1 (HSV-1) has been shown to possess both exonuclease and endonuclease activities in vitro, and deletion of most of the gene within the viral genome results in inefficient production and maturation of infectious virions, the function of the deoxyribonuclease (DNase) activity per se in virus replication remains unclear. In order to correlate the in vitro and in vivo activities of the protein encoded by UL12, mutant proteins were tested for nuclease activity in vitro by a novel hypersensitivity cleavage assay and for their ability to complement the replication of a DNase null mutant, AN-1. Rabbit reticulocyte lysates programmed with wild-type UL12 RNA cleaved at the same sites cleaved by purified HSV-1 DNase, but distinct from those cleaved by DNase 1 or micrococcal nuclease. All mutants which lacked DNase activity in vitro also failed to complement the replication of AN-1 in nonpermissive cells. Likewise, all mutants which contained HSV-1 DNase activity, as detected by the hypersensitivity cleavage assay, were capable of complementing the replication of the DNase null mutant, though to varying extents. Of particular note was the d1-126 mutant protein, which, despite having the same specific activity as the wild-type enzyme in vitro, complemented the replication of AN-1 significantly less than the wild-type protein. The results suggest that DNase activity per se is required for efficient replication of HSV-1 in vivo. However, residues, including the N-terminal 126 amino acids, which are dispensable for enzymatic activity in vitro may facilitate the accessibility or activity of the protein in vivo. 相似文献
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BB de Vries AM Wiegers E de Graaff AJ Verkerk JO Van Hemel DJ Halley JP Fryns LM Curfs MF Niermeijer BA Oostra 《Canadian Metallurgical Quarterly》1993,1(1):72-79
The fragile X mental retardation syndrome is caused by unstable expansion of a CGG repeat in the FMR-1 gene. Clinical expression is associated with a large expansion of the CGG repeat. The mutation in the FMR-1 gene and the cytogenetic expression of the fragile site at Xq27.3 have been studied in 52 fragile X male patients. The percentage of the cytogenetic expression of the fragile site at Xq27.3 positively correlates with the mean size of the full mutation in the FMR-1 gene (p < 0.0001) irrespective of the presence of additional premutation alleles. We noted a less frequent occurrence of additional premutation alleles in adult patients compared with juveniles, suggesting a continued mitotic instability in life. Additionally, the level of mental retardation has been ascertained in 35 patients using the Stanford-Binet or Terman-Merrill test of general intelligence. The presence of a full mutation in the FMR-1 gene seemed decisive for the occurrence of mental impairment in the patient. No correlation is observed between the degree of mental retardation and the size of the full mutation. The degree of mental retardation seemed not to be influenced by the presence of premutation alleles in part of the cells in addition to a full mutation. One patient is described with the 'Prader-Willi-like' subphenotype of the fragile X syndrome, showing a deletion in the FMR-1 gene in a part of his cells in addition to a full mutation. 相似文献
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AM Mulichak JO Hui AG Tomasselli RL Heinrikson KA Curry CS Tomich S Thaisrivongs TK Sawyer KD Watenpaugh 《Canadian Metallurgical Quarterly》1993,268(18):13103-13109
The crystal structure of human immunodeficiency virus (HIV) type 2 protease has been determined in complexes with peptidic inhibitors Noa-His-Cha psi [CH(OH)CH(OH)]Val-Ile-Amp (U75875) and Qnc-Asn-Cha psi [CH(OH)CH2]Val-Npt(U92163) (where Noa is naphthyloxyacetyl, Cha is cyclohexylalanine, Amp is 2-aminomethylpyridine, Qnc is quinoline-2-carbonyl, and Npt is neopentylamine), which have dihydroxyethylene and hydroxyethylene moieties, respectively, in place of the normal scissile bond of the natural ligand. The complexes crystallize in space group P2(1)2(1)2(1), with one dimer-inhibitor complex per asymmetric unit and average cell dimensions of a = 33.28 A, b = 45.35 A, c = 135.84 A. Data were collected to approximately 2.5-A resolution. The model structures were refined with resulting R-factors of around 0.19. As expected, the HIV-2 protease structure is approximately C2-symmetric with a gross structure very similar to that of the HIV-1 enzyme. The inhibitors bind in an extended conformation positioned lengthwise in the binding cleft in a manner similar to that found in the HIV-1 protease-inhibitor complexes previously reported. The substitution of the bulkier Ile82 side chain in the HIV-2 protease may help explain the better ability of HIV-2 protease to bind and hydrolyze ligands with small P1 and P1' side groups. It appears that differences in specificity between the proteases of HIV-1 and HIV-2 are not merely a result of simple side chain substitutions, but may be complicated by differences in main chain flexibility as well. 相似文献
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JO Atkinson K Mahomed MA Williams GB Woelk S Mudzamiri NS Weiss 《Canadian Metallurgical Quarterly》1998,44(4):86-92
OBJECTIVE: To identify specific foods that predispose Zimbabwean women to a higher or lower risk of pre-eclampsia and/or eclampsia. DESIGN: A case control study was implemented. Participants were asked by questionnaire to recall the specific amounts of meats, poultry, fruits, fish, vegetables and dairy products they had consumed in the month prior to giving birth. SETTING: Harare Maternity Hospital, Harare, Zimbabwe between June of 1995 and April of 1996. SUBJECTS: 180 women clinically diagnosed with pre-eclampsia (144) or eclampsia (36), and 194 normotensive women without these conditions. MAIN OUTCOME MEASURES: Pre-eclampsia/eclampsia. RESULTS: There were few associations between consumption of specific food items and the occurrence of pre-eclampsia/eclampsia. Meat and fruit were the only foods found to be significantly associated with pre-eclampsia. Women who consumed 12 or more servings of meat per month were more likely to have pre-eclampsia/eclampsia when compared to women eating 11 servings of meat or less per month. While intake of bananas and mangos was unrelated to risk, women who consumed other fruits (i.e. apples, oranges, grapes, peaches, apricots, paw paw, and plums), were 1.7 (95% CI = 1.0 to 3.1) times more likely to develop pre-eclampsia/eclampsia as women who ate none of these fruits. However, women who consumed relatively large quantities of these fruits were not at a particularly high risk. Increased consumption of kapenta was modestly associated with a decrease in disease risk, but this finding was well within the limits of chance and no association was present with intake of other types of fish. CONCLUSIONS: Our findings suggest that variation in consumption of specific foods do not have a strong effect on the incidence of pre-eclampsia in this population. However, further research involving the use of a more comprehensive dietary measure, biochemical measurements of nutrients, pre-pregnancy assessment and ascertainment of dietary intake prior to the development of pre-eclampsia are needed. 相似文献
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J Campisi GP Dimri JO Nehlin A Testori K Yoshimoto 《Canadian Metallurgical Quarterly》1996,31(1-2):7-12
Replicative senescence is a fundamental feature of most, if not all, somatic higher eukaryotic cells. The phenomenon has been studied for more than three decades, during which time the genetics and cell biology of senescent cells were characterized. In recent years, progress has been made on understanding the molecular basis for replicative senescence. At present, we now have a good, albeit still incomplete, understanding of some of the immediate causes for the growth arrest of senescent cells. The challenges for the future will be to understand the molecular bases for the prime causes of senescent phenotype, including the growth arrest and the altered differentiation. 相似文献
110.
Growth hormone (rGH) and prolactin (rPRL) secretory profiles were obtained before and after treatment with a dopamine receptor blocking agent, (+) butaclamol, in 10 male rats chronically implanted with right atrial cannulae. Mean rGH plasma concentrations, determined by planimetry, were reduced (202 +/- 20 ng/ml vs. 135 +/- 20ng/ml, P less than .01), but the basic configuration and periodicity of rGH secretory bursts were unaltered. Mean rPRL plasma concentrations were elevated (11.1 +/- 2.1 ng/ml vs 65.5 +/- 8.1 ng/ml, P less than .0005), but rPRL episodic secretion was still apparent. It is concluded that dopaminergic neurons have a minor role in facilitating episodic rGH secretion. Furthermore, persisting episodic rPRL secretion in rats administered a dopamine antagonist suggests that rPRL feedback inhibition does not inactivitate the neural mechanism generating episodic rPRL secretion. 相似文献