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991.
Paula A. Clark Tracy Lester Sally Genet Alison M. Jones Rudi Hendriks Roland J. Levinsky Christine Kinnon 《Human genetics》1995,96(4):427-432
Mutations in the common gamma chain (c or IL2RG) of the interleukin-2, –4, –7, –9 and –15 receptors have been found to cause X-linked severe combined immunodeficiency (SCIDX1). We report here on the mutations identified in a further ten families. Two of the mutations identified have occurred twice in unrelated families, indicating two possible mutational hotspots. Seven of the mutations, which were identified by single-strand conformational polymorphism (SSCP) analysis, are point mutations, and the eighth is a small deletion. We also report on the first use of assays based on these mutations within IL2RG for unambiguous carrier determination. The consequences for the c proteins produced as a result of these mutations are discussed. 相似文献
992.
We used a genetic assay to monitor the behavior of sister chromatids during the cell cycle. We show that the ability to induce
sister chromatid exchanges (SCE) with ionizing radiation is maximal in budded cells with undivided nuclei and then decreases
prior to nuclear division. SCE can be induced in cells arrested in G2 using either nocodazole or cdc mutants. These data show that sister chromatids have two different states prior to nuclear division. We suggest that the
sister chromatids of cir. III, a circular derivative of chromosome III, separate (anaphase A) prior to spindle elongation
(anaphase B). Other interpretations are also discussed. SCE can be induced in cdc mutants that arrest in G2 and in nocodazole-treated cells, suggesting that mitotic checkpoints arrest cells prior to sister
chromatid separation.
Received: 3 July 1996 / Accepted: 4 October 1996 相似文献
993.
Development of microtopography in a semi-arid grassland: Effects of disturbance size and soil texture 总被引:2,自引:0,他引:2
Our objective was to evaluate effects of disturbance size and soil texture on the development of microtopography for a shortgrass plant community in north central Colorado USA. Disturbances, defined as the death of individual plants, were created in 1984 and 1985 to evaluate development through time of the small-scale pattern of perennial bunchgrasses and bare soil openings that characterize this semiarid grassland. Disturbed plots of three sizes (50, 100, 150 cm-diameter) comparable in size to naturally-occurring disturbances were produced by killing plants at two sites differing in soil texture (sandy loam, clay loam). Disturbed plots were not manipulated after being created. In 1993, a laser surveying instrument was used to measure heights of crowns of individual plants of the dominant species, the perennial bunchgrass Bouteloua gracilis ([H.B.K.] Lag. ex Griffiths), and bare soil openings between plants for two locations: within each disturbance and in the surrounding undisturbed landscape.Differences between crown heights of plants and bare soil openings were comparable for both the undisturbed landscape and inside disturbances indicating that small-scale microtopography had recovered within nine years after disturbance occurred. However, complete recovery to the undisturbed state had not occurred since crown heights of plants relative to bare soil openings were significantly less on disturbed than undisturbed locations. Differences in height between plant crowns and bare soil openings on disturbed plots increased as disturbance size increased, indicating greater soil redistribution with increasing plot size. Larger differences in height were also found on plots on the fine- than the coarse-textured soil, indicating the importance of soil particle size and plant cover type to the development of microtopography. Differences in height between microsites on disturbed plots were positively related to total plant cover and negatively related to cover of B. gracilis indicating the importance of this species to reducing erosion on disturbed areas.In this semiarid grassland, patterns in microtopography were heterogeneous, likely as a result of the small-scale redistribution of soil between bare soil openings and B. gracilis plants through time. Our results indicate that this redistribution of soil is affected by disturbance size, soil texture, and patchy plant cover. The major effect of small-scale disturbances on patterns in microtopography of the shortgrass steppe are causing plant death and exposing soil to erosional and depositional processes. 相似文献
994.
Debra D. Wright J. Heinrich Jessen Peter Burke Hector Gomez de Silva Garza 《Biotropica》1997,29(3):250-260
Enumeration of a one hectare plot at 900 m a.s.l in Papua New Guinea revealed 693 individuals of 228 tree and liana species ≥ 10 cm DBH. A 0.1 hectare subplot contained 302 individuals of 106 species 2.5 ≥ DBH < 10 cm. Lauraceae, Moraceae, and Myristicaceae were the most important families in both size classes. This site is very diverse compared with other tropical forests, and like other species-rich sites worldwide, it has high aseasonal rainfall and high rates of natural disturbance. 相似文献
995.
Three-dimensional analysis and ultrastructural design of mitotic spindles from the cdc20 mutant of Saccharomyces cerevisiae. 总被引:1,自引:0,他引:1
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E T O'Toole D N Mastronarde T H Giddings Jr M Winey D J Burke J R McIntosh 《Molecular biology of the cell》1997,8(1):1-11
The three-dimensional organization of mitotic microtubules in a mutant strain of Saccharomyces cerevisiae has been studied by computer-assisted serial reconstruction. At the nonpermissive temperature, cdc20 cells arrested with a spindle length of approximately 2.5 microns. These spindles contained a mean of 81 microtubules (range, 56-100) compared with 23 in wild-type spindles of comparable length. This increase in spindle microtubule number resulted in a total polymer length up to four times that of wild-type spindles. The spindle pole bodies in the cdc20 cells were approximately 2.3 times the size of wild-type, thereby accommodating the abnormally large number of spindle microtubules. The cdc20 spindles contained a large number of interpolar microtubules organized in a "core bundle." A neighbor density analysis of this bundle at the spindle midzone showed a preferred spacing of approximately 35 nm center-to-center between microtubules of opposite polarity. Although this is evidence of specific interaction between antiparallel microtubules, mutant spindles were less ordered than the spindle of wild-type cells. The number of noncore microtubules was significantly higher than that reported for wild-type, and these microtubules did not display a characteristic metaphase configuration. cdc20 spindles showed significantly more cross-bridges between spindle microtubules than were seen in the wild type. The cross-bridge density was highest between antiparallel microtubules. These data suggest that spindle microtubules are stabilized in cdc20 cells and that the CDC20 gene product may be involved in cell cycle processes that promote spindle microtubule disassembly. 相似文献
996.
Differential requirements for DNA replication in the activation of mitotic checkpoints in Saccharomyces cerevisiae.
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Checkpoints prevent inaccurate chromosome segregation by inhibiting cell division when errors in mitotic processes are encountered. We used a temperature-sensitive mutation, dbf4, to examine the requirement for DNA replication in establishing mitotic checkpoint arrest. We used gamma-irradiation to induce DNA damage and hydroxyurea to limit deoxyribonucleotides in cells deprived of DBF4 function to investigate the requirement for DNA replication in DNA-responsive checkpoints. In the absence of DNA replication, mitosis was not inhibited by these treatments, which normally activate the DNA damage and DNA replication checkpoints. Our results support a model that indicates that the assembly of replication structures is critical for cells to respond to defects in DNA metabolism. We show that activating the spindle checkpoint with nocodazole does not require prior progression through S phase but does require a stable kinetochore. 相似文献
997.
Cellular effects of phosphotyrosine-binding domain inhibitors on insulin receptor signaling and trafficking.
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S Giorgetti-Peraldi E Ottinger G Wolf B Ye T R Burke Jr S E Shoelson 《Molecular and cellular biology》1997,17(3):1180-1188
Shc and insulin receptor substrate 1 (IRS-1) are cytoplasmic substrates of tyrosine kinase receptors that engage, localize, and activate downstream SH2 enzymes. Each contains a phosphotyrosine-binding (PTB) domain that is structurally unrelated to SH2 domains. We have designed high-affinity, cellular inhibitors of the Shc PTB domain by incorporating nonnatural, phosphatase-resistant amino acids into short peptides. None of the inhibitors bind the IRS-1 PTB domain, consistent with distinct specificities for domains. The best inhibitor of the Shc domain was introduced by electroporation into Rat1 fibroblasts that express human insulin receptors. Insulin-stimulated phosphorylation of Shc was inhibited, with no effect on IRS-1, and downstream effects on mitogen-activated protein kinase and DNA synthesis were both inhibited. The PTB domain inhibitor had less influence on epidermal growth factor-induced effects and essentially no impact on serum- or phorbol ester-induced effects. The inhibitor did not affect insulin internalization and its degradation. We conclude that the PTB domain of Shc is critical for its phosphorylation by the insulin receptor, that Shc is an important mediator of insulin's mitogenic effects, and that Shc is not central to insulin receptor cycling in these cells. PTB domains can be inhibited selectively in cells and represent potential targets for drug discovery. 相似文献
998.
Raphael M. Ngure P. David Eckersall Francis W. Jennings Joanne M. Burke Michael J. Stear Peter G.E. Kennedy Max Murray 《Parasitology international》1997,46(4):247-254
Investigation of the pathophysiological role of the systemic cytokines, including interleukin-1, interleukin-6 and tumour necrosis factor , in the host response to infection with African trypanosomes is hampered by the low and transient concentrations of these cytokines in plasma. One of the actions of these cytokines is the stimulation of hepatocyte production of acute phase proteins such as serum amyloid-P and haptoglobin. These acute phase proteins are more stable in the circulation than the cytokines and can be measured as a means of assessing the systemic cytokine response in the trypanosome-infected host. The plasma concentrations of serum amyloid-P and haptoglobin were measured in an experimental mouse model of Trypanosoma brucei brucei infection. Both serum amyloid-P and haptoglobin, increased markedly following infection. Peak concentrations of serum amyloid-P at 125 μg/ml and haptoglobin at 2 g/l were attained 10 to 12 days after infection. Thereafter, serum amyloid-P concentration decreased to approximately 40 μg/ml while the haptoglobin concentration remained elevated at approximately 1.5 g/l. The reactions of the serum amyloid-P and haptoglobin following experimental Trypanosoma brucei brucei infection in mice demonstrate that a major acute phase response has occurred indicating that the systemic cytokine network has been activated. Further studies are required to identify whether the response is stimulated by the parasite or indirectly by tissue damage. 相似文献
999.
Ronald A Burke Michael G Hvizd Ty R Shockley 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1997,693(2):370
High-performance anion-exchange chromatography with pulsed amperometric detection (HPAE–PAD) was evaluated for the quantitation of polyglucose metabolites (DP2–DP7) in human plasma. The method was investigated for accuracy, precision, specificity, linearity, range and analyte stability. Samples were prepared by dilution into the standard range (0.1–10 μg/ml) followed by deproteinization using a 30?000 molecular mass cut-off filtration device. The limit of detection was 0.05 μg/ml for all metabolites. Method precision for DP2–DP7 varied from approximately 2% R.S.D. in the upper range to approximately 15% R.S.D. at the limit of quantitation. Samples were stable following one or two freeze–thaw cycles and, after preparation, they could be refrigerated for up to 72 h. Application of this method to clinical plasma samples from continuous ambulatory peritoneal dialysis (CAPD) patients administered one daily night-time intraperitoneal exchange of 2 l of 7.5% polyglucose solution for four weeks indicated that plasma levels of DP2, DP3 and DP4 increased from baseline levels of <0.01 g/l to steady-state levels of 1.2±0.3, 1.2±0.3 and 0.4±0.1 g/l (mean±S.D.), respectively. These steady state plasma levels for DP2 and DP3 are comparable to previously reported levels in patients administered daily overnight 7.5% polyglucose dialysis solution. 相似文献
1000.