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91.
Lipoprotein(a) in women twins: heritability and relationship to apolipoprotein(a) phenotypes.
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M A Austin C Sandholzer J V Selby B Newman R M Krauss G Utermann 《American journal of human genetics》1992,51(4):829-840
Lp(a) is a unique lipoprotein consisting of an LDL-like particle and a characteristic protein, apo(a). Increased levels of Lp(a) constitute a risk factor for coronary heart disease. Variation in the size of the apo(a) protein is a phenotype controlled by the apo(a) gene on chromosome 6 and is related to Lp(a) plasma levels. Based on 169 MZ and 125 DZ adult female twin pairs, this study's purpose was to estimate the proportion of the variation in Lp(a) levels that is due to genetic influences and to determine the extent to which the apo(a) locus explains this heritability. Lp(a) levels were significantly more similar in MZ twins than in DZ twins: mean co-twin differences were 3.9 +/- 5.7 mg/dl and 16.0 +/- 19.9 mg/dl (P less than .001), respectively. Intraclass correlations were .94 in MZ twins and .32 in DZ twins, resulting in a heritability estimate of .94 (P less than .001). Heritability was then calculated using only co-twins with the same apo(a) phenotype: the heritability estimate decreased to .45 but was still highly significant (P less than .001). Therefore, on the basis of heritability analysis of women twins, Lp(a) levels are almost entirely genetically controlled. Variation at the apo(a) locus contributes to this heritability, although other genetic factors could be involved. 相似文献
92.
93.
Crystal structure of a berenil-dodecanucleotide complex: the role of water in sequence-specific ligand binding. 总被引:8,自引:1,他引:7
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D G Brown M R Sanderson J V Skelly T C Jenkins T Brown E Garman D I Stuart S Neidle 《The EMBO journal》1990,9(4):1329-1334
The three-dimensional structure of a complex between the dodecanucleotide d(CGCGAATTCGCG) and the anti-trypanocidal drug berenil, has been determined to a resolution of 2.5 A. The structure has been solved by molecular replacement and refined to an R factor of 0.177. A total of 49 water molecules have been located. The drug is bound at the 5'-AAT-3' region of the oligonucleotide. At one end of the drug the amidinium group is in hydrogen-bonded contact with N3 of the adenine base complementary to the thymine of the AAT. The other amidinium group does not make direct interactions with the DNA. Instead, a water molecule mediates between them. This is in hydrogen-bonded contact with an amidinium nitrogen atom, N3 of the 5' end adenine base and the ring oxygen atom of an adjacent deoxyribose. Molecular mechanics calculations have been performed on this complex, with the drug at various positions along the sequence. These show that the observed position is only 0.8 kcal/mol higher in energy than the best position. It is suggested that there is a broad energy well in the AATT region for this drug, and that water molecules as well as the neighbouring sequence, will determine precise positioning. More general aspects of minor groove binding are discussed. 相似文献
94.
J.E. Graeber B.M. Glaser B.N.Y. Setty J.A. Jerdan R.W. Walenga M.J. Stuart 《Prostaglandins & other lipid mediators》1990,39(6)
We evaluated 15-hydroxyeicosatetraenoic acid (15-HETE), a major arachidonic acid product of vascular endothelium and leukocytes, for its effect on neovascularization. In a modified Boyden chamber assay, 15-HETE (10−7 M) sitmulated human retinal microvessel endothelial cell migration by 42 ± 10% (mean ± S.E.M., p<0.01). 12-HETE, a major arachidonic acid metabolite of platelets, had no such effect. Further studies in the rabbit corneal pocket assay revealed that 15-HETE stimulated neovascularization
. Concentrations at which the
effects were observed are within the range generated by several cell types and are achievable in human serum. 15-HETE stimulation of human endothelial cell migration
and neovascularization
suggests that it may play a role in vasoproliferative disorders. 相似文献
95.
Dianna M. Milewicz Peter H. Byers John Reveille Austin L. Hughes Madeleine Duvic 《Journal of molecular evolution》1996,42(2):117-123
Alu elements are a class of repetitive DNA sequences found throughout the human genome that are thought to be duplicated via an RNA intermediate in a process termed retroposition. Recently inserted Alu elements are closely related, suggesting that they are derived from a single source gene or closely related source genes. Analysis of the type III collagen gene (COL3A1) revealed a polymorphic Alu insertion in intron 8 of the gene. The Alu insertion in the COL3A1 gene had a high degree of nucleotide identity to the Sb family of Alu elements, a family of older Alu elements. The Alu sequence was less similar to the consensus sequence for the PV or Sb2 subfamilies, subfamilies of recently inserted Alu elements. These data support the observations that at least three source genes are active in the human genome, one of which is distinct from the PV and Sb2 subfamilies and predates either of these two subfamilies. Appearance of the Alu insertion in different ethnic populations suggests that the insertion may have occurred in the last 100,000 years. This Alu insert should be a useful marker for population studies and for marking COL3A1 alleles. 相似文献
96.
Efficient infection of cells in culture by type O foot-and-mouth disease virus requires binding to cell surface heparan sulfate. 总被引:21,自引:14,他引:7
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T Jackson F M Ellard R A Ghazaleh S M Brookes W E Blakemore A H Corteyn D I Stuart J W Newman A M King 《Journal of virology》1996,70(8):5282-5287
Foot-and-mouth disease virus (FMDV) enters cells by attaching to cellular receptor molecules of the integrin family, one of which has been identified as the RGD-binding integrin alpha(v)beta3. Here we report that, in addition to an integrin binding site, type O strains of FMDV share with natural ligands of alpha(v)beta3 (i.e., vitronectin and fibronectin) a specific affinity for heparin and that binding to the cellular form of this sulfated glycan, heparan sulfate, is required for efficient infection of cells in culture. Binding of the virus to paraformaldehyde-fixed cells was powerfully inhibited by agents such as heparin, that compete with heparan sulfate or by agents that compete for heparan sulfate (platelet factor 4) or that inactivate it (heparinase). Neither chondroitin sulfate, a structurally related component of the extracellular matrix, nor dextran sulfate appreciably inhibited binding. The functional importance of heparan sulfate binding was demonstrated by the facts that (i) infection of live cells by FMDV could also be blocked specifically by heparin, albeit at a much higher concentration of inhibitor; (ii) pretreatment of cells with heparinase reduced the number of plaques formed compared with that for untreated cells; and (iii) mutant cell lines deficient in heparan sulfate expression were unable to support plaque formation by FMDV, even though they remained equally susceptible to another picornavirus, bovine enterovirus. The results show that entry of type O FMDV into cells is a complex process and suggest that the initial contact with the cell surface is made through heparan sulfate. 相似文献
97.
Structure and function in the herpes simplex virus 1 RNA-binding protein U(s)11: mapping of the domain required for ribosomal and nucleolar association and RNA binding in vitro. 总被引:2,自引:2,他引:0
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The herpes simplex virus 1 US11 protein is an RNA-binding regulatory protein that specifically and stably associates with 60S ribosomal subunits and nucleoli and is incorporated into virions. We report that US11/ beta-galactosidase fusion protein expressed in bacteria bound to rRNA from the 60S subunit and not the 40S subunit. This binding reflects the specificity of ribosomal subunit association. Analyses of deletion mutants of the US11 gene showed that specific RNA binding activity, nucleolar localization, and association with 60S ribosomal subunits were found to map to the amino acid sequences of the carboxyl terminus of US11 protein, suggesting that these activities all reflect specific binding of US11 to large subunit rRNA. The carboxyl-terminal half of the protein consists of a regular tripeptide repeat of the sequence RXP and constitutes a completely novel RNA-binding domain. All of the mutant US11 proteins could be incorporated into virus particles, suggesting that the signal for virion incorporation either is at the amino-terminal four amino acids or is redundant in the protein. 相似文献
98.
Dissolved organic carbon (DOC) dynamics were examined over five years (1989–1993) in Sycamore Creek, a Sonoran Desert stream, specifically focusing on DOC concentration in surface and hyporheic waters, and rates of export. In 1989 and 1990, the years of lowest stream discharge (0.08 and 0.04 m3 s–1 annual mean of daily discharge, respectively), DOC was high, averaging 7.37 and 6.22 mgC l–1 (weighted annual means). In contrast, from 1991 through 1993, a period of increased flow (1.1, 1.2 and 4.3 m3 s–1), concentration was significantly lower (P<0.001) with annual mean concentrations of 3.54, 3.49 and 3.39 mgC l–1. Concentration exhibited little spatial variation between two sampling stations located 6 km apart along the mainstem or between surface and hyporheic waters. Annual export of DOC from Sycamore Creek varied 100-fold over the five-year period from a mean rate of only 24 kgC d–1 in 1990 to 2100 kgC d–1 in 1993. Ninety percent of DOC was exported by flows greater than 2.8 m3 s–1, and 50% during flows greater than 27 m3 s–1; flows of 2.8 and 24 m3 s–1 occurred only 9 and 1% of the time. The export of organic matter in Sycamore Creek appears to be coupled to El Niño-Southern Oscillation phenomena. The years of highest export, 1991–1993, had El Niño conditions while 1989 and 1990 had medial conditions. 相似文献
99.
100.
The hypothalamic-pituitary-adrenal (HPA) axis normally maintains the concentration of Cortisol within a narrow range with a diurnal variation characterized by higher Cortisol concentrations in the morning and reduced levels in the evening. Excessive or deficient secretion of Cortisol is associated with pathologic changes. Obesity has been linked with age, sex and racial alterations in the functioning of the HP A axis which are reviewed. The possible relationship of altered HPA axis activity with the long-term complications of obesity are considered. 相似文献