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81.
Demin Wang Elizabeth C. Boylin Yoshiyuki Minegishi Renren Wen Edvard C. Smith James N. Ihle Mary Conley 《Immunogenetics》2001,53(7):550-556
Our recent studies using targeted gene disruption have shown that defects in phospholipase Cgamma2 (PLCgamma2) result in a B-cell abnormality that is very similar to that seen in Btk-deficient mice. Null mutations in either PLCG2 or BTK are associated with decreased numbers of mature B cells, failure to make antibodies to some T cell-independent antigens and the absence of CD5+ peritoneal B cells. Mutations in BTK in humans cause a more severe defect in B-cell development characterized by almost complete absence of B cells in the peripheral circulation, profound hypogammaglobulinemia and an inability to produce antibodies to any antigens. However, not all patients with severe defects in B-cell development have mutations in BTK or the components of the B-cell signal transduction complex. To explore the possibility that some patients with defects in B-cell development of unknown etiology might have mutations in PLCG2, we determined the genomic structure of this gene and established conditions to analyze the 32 exons of the gene and the flanking sequences by single-strand conformation polymorphism. Although 24 polymorphic variants of this gene were found in 35 patients, we did not identify any alterations that were likely to be the cause of disease. 相似文献
82.
B A Conley P S Callery M J Egorin B Subramanyam L A Geelhaar S S Pan 《Life sciences》1988,43(9):793-800
We have previously demonstrated a number of metabolites of hexamethylene bisacetamide (HMBA) in the urine of patients treated with HMBA. These include N-acetyl-1,6-diaminohexane (NADAH), 6-acetamidohexanoic acid (6AcHA), 1,6-diaminohexane (DAH) and 6-aminohexanoic acid (6AmHA). Because these compounds have potential roles in the dose-limiting metabolic acidosis and neurotoxicity associated with HMBA therapy, and are similar in structure to known substrates of monoamine oxidase (MAO) and diamine oxidase (DAO), we investigated the activities of these enzymes in the metabolic interconversion of HMBA metabolites. NADAH (5 mM) was incubated with MAO and aldehyde dehydrogenase. 6AcHA production was verified by gas chromatography-mass spectrometry and quantified by gas chromatography. 6AcHA production was linear for up to 4 hr. Complete inhibition of MAO activity was observed with 2 mM tranyl-cypromine or pargyline. Mouse liver microsomes, which do not contain MAO, did not convert NADAH to 6AcHA and, in control experiments, did not degrade 6AcHA. The HMBA metabolite, DAH, was a substrate for DAO, producing 3,4,5,6-tetrahydro-2H-azepine. Participation of DAO in the metabolism of HMBA implies potential interaction of HMBA and metabolites with polyamine metabolism and may represent a mechanism for HMBA's effects on cellular growth and differentiation. Metabolism of NADAH, also a differentiator, by MAO implies that concurrent use of HMBA and an MAO inhibitor may be clinically useful. 相似文献
83.
The effect of eutrophication on particulate amorphous silica (ASi) sequestration was isolated and quantified in Lake St. Croix and Lake Pepin, two natural, human-impacted impoundments of the upper Mississippi River. In contrast to impoundments behind engineered dams, where silica (Si) fluxes may be changed by various aspects of dam construction, these two riverine lakes have long (9,000+ years) sedimentary sequences that record the entire span of cultural eutrophication and the resulting silica sequestration. The concentrations of dissolved silicate (DSi) and ASi in the lake inflows were measured for 1 year to obtain the total flux of bioavailable silica (TSib = DSi + ASi) to each impoundment. Historical rates of Si sequestration in each lake were determined using ASi burial in multiple sediment cores and modeled estimates of historical TSib fluxes. The Si trapping efficiency of each lake was found to have increased exponentially with cultural eutrophication (estimated two- to fivefold increase in Lake St. Croix and 9- to 16-fold increase in Lake Pepin over the last 100 years), indicating the degree to which eutrophication of impoundments can reduce silica export to downstream coastal and marine ecosystems. Because these two lakes presently exhibit different degrees of eutrophication, together they depict a relationship between phosphorus concentration and Si trapping efficiency that may be applied to other impoundments, including human-made reservoirs. 相似文献
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85.
Sheryl Coombs Ruth A. Conley 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》1997,180(4):401-415
Extracellular, single unit recording techniques were used to measure the responses of posterior lateral line nerve fibers
to a 50-Hz dipole source that slowly changed its location along the length of the fish. The flow-field equations for a dipole
source were used to model the pressure gradient pattern and thus, the expected excitation pattern along a linear array of
lateral line receptor organs for different source locations. Finally, excitation patterns were similarly modeled along the
left and right side of the fish's head for actual steps taken by sculpin in approach pathways to the 50-Hz dipole source.
Spatial histograms of posterior lateral line nerve fiber responses to different locations of the dipole source could be predicted
from pressure gradient patterns modeled from the flow-field equations, confirming that the modeling approach applied to behavioral
results was a good predictor of excitation patterns likely to be encoded by the lateral line periphery. An examination of
how modeled excitation patterns changed from one position to the next in typical approach pathways and how patterns differed
between positions from which successful and unsuccessful strikes were launched suggests that approach and strike strategies
can indeed be explained by the information available in excitation patterns. In particular, changes in the spatial distribution
of pressure gradient directions (polarities), available only when the source is lateral (as opposed to directly in front of
the fish), appear to enhance the ability of sculpin to determine source distance. Without such information, misses are more
likely to occur and successful strikes are more likely to be launched from short distances only.
Accepted: 23 October 1996 相似文献
86.
This paper focuses on several aspects of the specificity of mutants of Escherichia coli glutaminyl-tRNA synthetase (GlnRS) and tRNA(Gln). Temperature-sensitive mutants located in glnS, the gene for GlnRS, have been described previously. The mutations responsible for the temperature-sensitive phenotype were analyzed, and pseudorevertants of these mutants isolated and characterized. The nature of these mutations is discussed in terms of their location in the three-dimensional structure of the tRNA(Gln).GlnRS complex. In order to characterize the specificity of the aminoacylation reaction, mutant tRNA(Gln) species were synthesized with either a 2'-deoxy AMP or 3'-deoxy AMP as their 3'-terminal nucleotide. Subsequent assays for aminoacylation and ATP/PPi exchange activity established the esterification of glutamine to the 2'-hydroxyl of the terminal adenosine; there is no glutaminylation of the 3'-OH group. This correlates with the classification of GlnRS as a class I aminoacyl-tRNA synthetase. Mutations in tRNA(Gln) are discussed which affect the recognition of GlnRS and the current concept of glutamine identity in E coli is reviewed. 相似文献
87.
Water Deficit Rapidly Stimulates the Activity of a Protein Kinase in the Elongation Zone of the Maize Primary Root 总被引:12,自引:1,他引:11
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The mechanisms by which plants detect water deficit and transduce that signal into adaptive responses is unknown. In maize (Zea mays L.) seedlings, primary roots adapt to low water potentials such that substantial rates of elongation continue when shoot growth is completely inhibited. In this study, in-gel protein kinase assays were used to determine whether protein kinases in the elongation zone of the primary root undergo activation or inactivation in response to water deficit. Multiple differences were detected in the phosphoprotein content of root tips of water-stressed compared with well-watered seedlings. Protein kinase assays identified water-deficit-activated protein kinases, including a 45-kD, Ca2+-independent serine/threonine protein kinase. Water-deficit activation of this kinase occurred within 30 min after transplanting seedlings to conditions of low water potential and was localized to the elongation zone, was independent of ABA accumulation, and was unaffected by cycloheximide-mediated inhibition of protein translation. These results provide evidence that the 45-kD protein kinase acts at an early step in the response of maize primary roots to water deficit and is possibly involved in regulating the adaptation of root growth to low water potential. 相似文献
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