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61.
Temperature-Sensitive Lethal Mutations on Yeast Chromosome I Appear to Define Only a Small Number of Genes 总被引:16,自引:4,他引:12
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David B. Kaback Paul W. Oeller H. Yde Steensma Janet Hirschman Diane Ruezinsky Kevin G. Coleman John R. Pringle 《Genetics》1984,108(1):67-90
A method was developed for isolating large numbers of mutations on chromosome I of the yeast Saccharomyces cerevisiae. A strain monosomic for chromosome I (i.e., haploid for chromosome I and diploid for all other chromosomes) was mutagenized with either ethyl methanesulfonate or N-methyl-N'-nitro-N -nitrosoguanidine and screened for temperature-sensitive (Ts- ) mutants capable of growth on rich, glucose-containing medium at 25° but not at 37°. Recessive mutations induced on chromosome I are expressed, whereas those on the diploid chromosomes are usually not expressed because of the presence of wild-type alleles on the homologous chromosomes. Dominant ts mutations on all chromosomes should also be expressed, but these appeared rarely. — Of the 41 ts mutations analyzed, 32 mapped on chromosome I. These 32 mutations fell into only three complementation groups, which proved to be the previously described genes CDC15, CDC24 and PYK1 (or CDC19). We recovered 16 or 17 independent mutations in CDC15, 12 independent mutations in CDC24 and three independent mutations in PYK1. A fourth gene on chromosome I, MAK16, is known to be capable of giving rise to a ts-lethal allele, but we recovered no mutations in this gene. The remaining nine mutations isolated using the monosomic strain appeared not to map on chromosome I and were apparently expressed in the original mutants because they had become homozygous or hemizygous by mitotic recombination or chromosome loss. — The available information about the size of chromosome I suggests that it should contain approximately 60–100 genes. However, our isolation in the monosomic strain of multiple, independent alleles of just three genes suggests that only a small proportion of the genes on chromosome I is easily mutable to give a Ts--lethal phenotype. — During these studies, we located CDC24 on chromosome I and determined that it is centromere distal to PYK1 on the left arm of the chromosome. 相似文献
62.
Summary The Na+ requirement for active, electrogenic Cl– absorption byAmphiuma small intestine was studied by tracer techniques and double-barreled Cl–-sensitive microelectrodes. Addition of Cl– to a Cl–-free medium bathingin vitro intestinal segments produced a saturable (K
m
=5.4mm) increase in shortcircuit current (I
sc) which was inhibitable by 1mm SITS. The selectivity sequence for the anion-evoked current was Cl–=Br–>SCN–>NO
3
–
>F–=I–. Current evoked by Cl– reached a maximum with increasing medium Na concentration (K
m
=12.4mm). Addition of Na+, as Na gluconate (10mm), to mucosal and serosal Na+-free media stimulated the Cl– current and simultaneously increased the absorptive Cl– flux (J
ms
Cl
) and net flux (J
net
Cl
) without changing the secretory Cl– flux (J
sm
Cl
). Addition of Na+ only to the serosal fluid stimulatedJ
ms
Cl
much more than Na+ addition only to the mucosal fluid in paired tissues. Serosal DIDS (1mm) blocked the stimulation. Serosal 10mm Tris gluconate or choline gluconate failed to stimulateJ
ms
Cl
. Intracellular Cl– activity (a
Cl
i
) in villus epithelial cells was above electrochemical equilibrium indicating active Cl– uptake. Ouabain (1mm) eliminated Cl– accumulation and reduced the mucosal membrane potential
m
over 2 to 3 hr. In contrast, SITS had no effect on Cl– accumulation and hyperpolarized the mucosal membrane. Replacement of serosal Na+ with choline eliminated Cl– accumulation while replacement of mucosal Na+ had no effect. In conclusion by two independent methods active electrogenic Cl– absorption depends on serosal rather than mucosal Na+. It is concluded that Cl– enters the cell via a primary (rheogenic) transport mechanism. At the serosal membrane the Na+ gradient most likely energizes H+ export and regulates mucosal Cl– accumulation perhaps by influencing cell pH or HCO
3
–
concentration. 相似文献
63.
Sulfhydryl Groups in Receptor Binding of Thyrotropin-Releasing Hormone to Rat Amygdala 总被引:2,自引:1,他引:1
Abstract: Binding of [3 H]-[3-Me-His2 ]thyrotropin-releasing hormone ([3 H]MeTRH) to TRH receptors in rat amygdala was decreased by sulfhydryl reagents in a time-, temperature-, and concentration-dependent manner. A pronounced reduction in receptor density, with little or no change in binding affinity, was apparent following disulfide bond reduction by dithiothreitol (DTT), alkylation of thiol groups by N -ethylmaleimide (NEM), and their oxidation by 5,5'-dithiobis (2-nitrobenzoic acid). Heavy metals (Cd2+ , Hg2+ ), which complex with reactive -SH residues, also potently inhibited binding. The pharmacological specificity of residual [3 H]MeTRH binding in chemically modified amygdala membranes was the same as that in control preparations. Sequential exposure to thiol reagents, in the presence or absence of cations, revealed possible additive effects. Pretreatment of membranes with TRH (10- -8 -- 10- -6 M ), and its continued presence during modification, afforded protection against DTT and NEM. These results indicate the possible importance of thiol groups in the maintenance of TRH receptor conformation. 相似文献
64.
The benzodiazepines (BZDs) chlordiazepoxide (CDE), diazepam (DZM), and flurazepam (FLM) inhibited receptor binding for thyrotropin-releasing hormone (TRH) with low micromolar potency. In contrast, numerous other categories of drugs were previously shown to be inactive. Scatchard analysis of competition data suggested that the BZDs reduced TRH receptor affinity, consistent with competitive inhibition. Receptors from amygdala, retina, and pituitary appeared more sensitive to inhibition by BZDs than those from hypothalamus, hippocampus, spinal cord, or cerebellum. The latter four regions also gave shallower inhibition curves. CDE revealed an apparently biphasic dissociation of [3-Me-His2]TRH([3H]MeTRH) from amygdala membranes at 4 degrees C, with kinetics similar to those with TRH. These results suggest that TRH receptors in the brain are heterogeneous and that certain BZDs in high therapeutic concentrations may exert central effects through actions at TRH receptors or coupled proteins. 相似文献
65.
66.
67.
N A Sharif N S Pilotte D R Burt 《Biochemical and biophysical research communications》1983,116(2):669-674
Receptors for thyrotropin-releasing hormone (pGlu-His-Pro-NH2, TRH) on thaw-mounted sections of rabbit spinal cord have been identified biochemically and visualized by light microscopic autoradiography. Binding of [3H] [3-Me-His2]TRH to 20 microns sections exhibited high apparent affinity and a pharmacological specificity almost identical to that previously demonstrated for spinal TRH receptors in membranes. In autoradiograms, the highest density of TRH receptors appeared in the substantia gelatinosa of the dorsal gray and around the central canal, with intermediate levels in the ventral gray. 相似文献
68.
Some properties of monolayers of (POPG) alone or of POPG in mixtures with (DPPC) have been measured near 35°C during dynamic compression and expansion at 3.6 cm2·s?1. (2) The mean values of minimum surface tension (corresponding to maximum surface pressure) which could be obtained with pure POPG monolayers at high compression ranged from 15 to 18 mN·m?1 in the presence of Na+, Ca2+ or low pH (2.0) in the subphase. (3) The presence of Ca2+ or low pH in the subphase increased the collapse plateau ratios obtained on cyclic compression. This might represent enhanced respreading into the monolayer of pure POPG from a collapsed form during reexpansion of the surface. (4) Monolayers containing 10% or 30% POPG and 90% or 70% DPPC could be compressed to surface tensions approaching zero. (5) In such mixed monolayers, 10% or 30% POPG did not appear to enhance respreading, as measured by collapse plateau ratios, in the presence of Na+ or Ca2+ in the subphase. 相似文献
69.
The activity of the hydrophilic Vibrio sp. strain DW1 and the hydrophobic Pseudomonas sp. strain S9, which both undergo starvation-induced responses, was examined at nutrient-enriched and nutrient-deficient interfaces. The initial period of response to a starvation regime (“dwarfing” phase) is a sequence of two processes: fragmentation and continuous size reduction of the fragmented cells. This dwarfing phase is also one of intense metabolic activity as supported by O2 uptake measurements of the endogenous metabolism and the use of inhibitors of the proton flow, the electron transport chain, and membrane-bound ATPase. Hydrophilic bacteria become even smaller at nutrient-deficient surfaces than in the liquid phase upon starvation, and this is reflected in a higher endogenous metabolism exhibited by surface-associated cells compared with those in the liquid phase. On the other hand, hydrophobic bacteria dwarfing at surfaces did not exhibit a greater size reduction and exhibited an endogenous metabolism that was only slightly higher than that of cells in the liquid phase. Bacterial scavenging of surface-localized nutrients is related to the degree of irreversible binding of dwarf and starved bacteria, which in turn may be related to the degree of cell surface hydrophobicity. 相似文献
70.
Kevin D. Reilly 《Bulletin of mathematical biology》1968,30(4):565-579
A mathematical model for learning of a conditioned avoidance behavior is presented. An identification of the net excitation
of a neural model (Rashevsky, N., 1960.Mathematical Biophysics. Vol. II. New York: Dover Publications, Inc.) with the instantaneous probability of response is introduced and its usefulness
in discussing block-trial learning performances in the conditioned avoidance situation is outlined for normal and brain-operated
animals, using experimental data collected by the author. Later, the model is applied to consecutive trial learning and connection
is made with the approach of H. D. Landahl (1964. “An Avoidance Learning Situation. A Neural Net Model.”Bull. Math. Biophysics,26, 83–89; and 1965, “A Neural Net Model for Escape Learning.”Bull. Math. Biophysics,27, Special Edition, 317–328) wherein lie further data with which the model can be compared. 相似文献