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51.
The teratogenic effects of valproic acid and its 4-propyl-4-pentenoic acid (4-en) metabolite were investigated in three inbred mouse strains that were known to possess differing sensitivity to heat-induced neural tube defects. In the heat-resistant DBA/2J strain, administration of either valproic acid or the metabolite during the critical period of neural tube development failed to produce any abnormal offspring. Similar treatment in the moderately heat-sensitive LM/Bc strain resulted in up to 19.8% exencephalic fetuses. The highly heat-sensitive SWV strain was also very susceptible to the induction of neural tube defects by either valproic acid or its 4-en metabolite. When administered on gestational day 8 plus 12 hours, the parent compound produced 35% exencephalic fetuses, while the metabolite had a response frequency of 32.4%. Thus, the hierarchy of susceptibility for the induction of neural tube defects in these inbred mouse strains was exactly the same whether the teratogen was a physical agent such as hyperthermia or a chemical compound such as valproic acid. If such diverse agents as these should interact to produce malformations, then it is possible that a wide variety of other agents might interact in a similar manner to produce neural tube defects. 相似文献
52.
D. A. Laurie M. D. Bennett 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》1988,76(3):393-397
Summary Hybrid embryos from hexaploid wheat x maize crosses rapidly lose the maize chromosomes to produce haploid wheat embryos. Such embryos almost always aborted when left to develop on the plant, and only 1 was recovered from 2440 florets (0.17% of the expected number). Embryos had greater viability in spikelet culture, 47 (26.5% of the expected number) being recovered from 706 ovaries. Thirty-two of these embryos germinated to give green plants, 31 of which were haploid (21 wheat chromosomes) and 1 of which was euploid (42 wheat chromosomes). Spikelet culture enabled 17.1% of the expected number of embryos to be recovered as haploid plants, a 100-fold improvement on allowing embryos to develop in vivo. Ten haploid plants of Chinese Spring (kr1, kr2), 13 plants of Chinese Spring (Hope 5A) (kr1, Kr2), and 8 of Hope (Kr1, Kr2) were recovered. The potential of wheat x maize crosses for wheat haploid production and for gene transfer from maize to wheat is discussed. 相似文献
53.
Structure-function analysis of hepatocyte growth factor: identification of variants that lack mitogenic activity yet retain high affinity receptor binding. 总被引:11,自引:0,他引:11
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N A Lokker M R Mark E A Luis G L Bennett K A Robbins J B Baker P J Godowski 《The EMBO journal》1992,11(7):2503-2510
Hepatocyte growth factor (HGF) is a potent mitogen for parenchymal liver, epithelial and endothelial cells. Structurally, it has similarities to kringle-containing serine proteases, although it does not possess proteolytic activity. A structure-activity relationship study of human HGF was performed by functional analysis of HGF substitution and deletion variants. Analysis of HGF variants was accomplished by defining their ability to induce DNA synthesis on hepatocytes in primary culture and to compete with wild-type HGF for binding to a soluble form of the HGF receptor. Three groups of variants were made: (i) substitutions at the cleavage site, (ii) substitutions within the protease-like domain and (iii) deletions of the beta-chain and/or kringle domains. Our results show that: (i) single-chain HGF is a zymogen-like promitogen in that cleavage into a two-chain form is required for biological activity, however, the single chain form of HGF still retains substantial receptor binding capacity; (ii) certain mutations in the protease-like domain result in variants that are completely defective for mitogenic activity, yet exhibit apparent receptor binding affinities similar to wild-type HGF (Kd approximately 50-70 pM); and (iii) a variant containing the N-terminal 272 residues of mature HGF showed only a 4-fold increase in Kd when compared with wild-type HGF indicating that a primary receptor binding determinant is located within this sequence. 相似文献
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55.
Summary Aberrations of photoreceptor ultrastructure resulting from carotenoid/retinoid (vitamin A) deprivation were studied in the retina of Manduca sexta. The syndrome of chromophore deficiency included hypertrophy of smooth endoplasmic reticulum, variable dilation of rhabdomeric microvilli, the insertion of endomembrane fingers into such enlarged microvilli, and the formation of rhabdomeric vacuoles, intracellular compartments containing microvilli similar to those of the rhabdomere. Retinas were processed either with conventional procedures employing preliminary aldehyde fixation followed by heavy metal postfixation, or by fixation and incubation in unbuffered OsO4. The latter method deposits osmium throughout the endomembrane system, within the rhabdomeric vacuoles, and in the extracellular space of the rhabdom. However, the intravillous fingers were rarely impregnated with osmium, despite their continuity with densely stained cisternae of the smooth endoplasmic reticulum. We suggest that the insertion of endomembrane fingers into dilated microvilli results from a cytoskeleton-mediated link between cisternae of the smooth endoplasmic reticulum and the rhabdomeric membrane, an association that may be important in the turnover of photoreceptor membrane. We interpret endomembrane hypertrophy and development of rhabdomeric vacuoles as symptoms of disturbance in the pathway leading to the assembly of the rhabdomere resulting from reduced synthesis of visual pigment. 相似文献
56.
In Phaseolus vulgaris L. (French bean) glutamine synthetase (GS) is encoded by four closely-related genes termed gln-alpha, gln-beta, gln-gamma and gln-delta. We have constructed and characterised in vitro a number of hammerhead ribozymes designed to cleave individual RNAs encoded by these genes. The three ribozymes, termed J1, J2 and J3, were targeted to cleave RNA at the start of the gamma and beta, and the middle of the gamma, GS open reading frames respectively. All three ribozymes successfully discriminated between the four (alpha, beta, gamma and delta) highly homologous sequences, even though the targeted sites of cleavage shared up to 18 out of 22 identical bases with other gene family members. The ribozyme-mediated cleavage reactions were Mg2+ dependent and enhanced at higher temperatures, although the J1 ribozyme retained considerable activity at physiological temperatures. Both J1 and J2 demonstrated a time-dependent cleavage of their targeted GS RNAs, although these two ribozymes differed markedly in their ability to cleave multiple substrate molecules. The rate of cleavage by J1 was found to be reduced in the presence of related GS RNAs and by total leaf poly(A) RNAs. The implications of these results for ribozyme activity in vivo are discussed. 相似文献
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58.
Sink Metabolism in Tomato Fruit : IV. Genetic and Biochemical Analysis of Sucrose Accumulation 总被引:9,自引:8,他引:1
Fruit of domesticated tomato (Lycopersicon esculentum) accumulate primarily glucose and fructose, whereas some wild tomato species, including Lycopersicon chmielewskii, accumulate sucrose. Genetic analysis of progeny resulting from a cross between L. chmielewskii and L. esculentum indicated that the sucrose-accumulating trait could be stably transferred and that the trait was controlled by the action of one or two recessive genes. Biochemical analysis of progeny resulting from this cross indicated that the sucrose-accumulating trait was associated with greatly reduced levels of acid invertase, but normal levels of sucrose synthase. Invertase from hexose-accumulating fruit was purified and could be resolved into three isoforms by chromatofocusing, each with isoelectric points between 5.1 and 5.5. The invertase isoforms showed identical polypeptide profiles on sodium dodecyl sulfate polyacrylamide gel electrophoresis, consisting of a primary 52 kilodalton polypeptide and two lower molecular mass polypeptides that appear to be degradation products of the 52 kilodalton polypeptide. The three invertase isoforms were indistinguishable based on pH, temperature, and substrate concentration dependence. Immunological detection of invertase indicated that the low level of invertase in sucrose-accumulating fruit was due to low levels of invertase protein rather than the presence of an invertase inhibitor. Based on comparison of genetic and biochemical data we speculate that a gene either encoding tomato fruit acid invertase or one required for its expression, plays an important role in determining sucrose accumulation. 相似文献
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60.
N. C. Bennett 《Journal of Zoology》1992,228(3):435-443
The locomotory activity patterns of a colony of eight field-captured mole-rats housed in a transparent burrow system were monitored for a total of 240 hours. Movement along the burrow system was recorded for all hours of the 24-hour chronological day for 10 days. Intermittent periods of activity were characteristic for all the mole-rats in the colony. The lack of a distinct sleeping period reflects the asynchrony of each mole-rat's activity cycle with that of other colony members. There are four major peaks of activity during the 24-hour cycle and an absence of a well-defined diurnal or nocturnal phase to the activity cycle.
The nest area is a focal point in the burrow system with individuals spending between 36 and 81% of the day there. There is a positive correlation between the size of a group of sleeping mole-rats in the nest and the frequency of occurrence. 相似文献
The nest area is a focal point in the burrow system with individuals spending between 36 and 81% of the day there. There is a positive correlation between the size of a group of sleeping mole-rats in the nest and the frequency of occurrence. 相似文献