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Victoria V. Hargreaves Scarlet S. Shell Dan J. Mazur Martin T. Hess Richard D. Kolodner 《The Journal of biological chemistry》2010,285(12):9301-9310
Indirect evidence has suggested that the Msh2-Msh6 mispair-binding complex undergoes conformational changes upon binding of ATP and mispairs, resulting in the formation of Msh2-Msh6 sliding clamps and licensing the formation of Msh2-Msh6-Mlh1-Pms1 ternary complexes. Here, we have studied eight mutant Msh2-Msh6 complexes with defective responses to nucleotide binding and/or mispair binding and used them to study the conformational changes required for sliding clamp formation and ternary complex assembly. ATP binding to the Msh6 nucleotide-binding site results in a conformational change that allows binding of ATP to the Msh2 nucleotide-binding site, although ATP binding to the two nucleotide-binding sites appears to be uncoupled in some mutant complexes. The formation of Msh2-Msh6-Mlh1-Pms1 ternary complexes requires ATP binding to only the Msh6 nucleotide-binding site, whereas the formation of Msh2-Msh6 sliding clamps requires ATP binding to both the Msh2 and Msh6 nucleotide-binding sites. In addition, the properties of the different mutant complexes suggest that distinct conformational states mediated by communication between the Msh2 and Msh6 nucleotide-binding sites are required for the formation of ternary complexes and sliding clamps. 相似文献
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Oswald Hess 《Molecular & general genetics : MGG》1970,107(3):224-242
Summary The phenotype of the variegation position effect white-mottled-2 in Drosophila hydei is modified by supernumerary Y chromosomes and by fractions thereof. Different translocated Y fragments have varying degrees of effectiveness in suppressing the mutant phenotype in the mottled eyes. In fragments derived from similar regions of the Y chromosome the suppressive ability is related to their cytological lengths. In contrast, fragments derived from distinctive regions of the Y chromosome differ markedly in their effectiveness, and these differences are not necessarily correlated with the cytological length. In particular, fragments of the distal region of YL are more effective in enhancing the wild phenotype than are proximal fragments of similar size.The mutation white-mottled-2 is accompanied by a complex rearrangement of the X chromosome. This inhibits crossing over between large regions of the X chromosome in structural heterozygotes; it causes also a delay of development and a considerable reduction of viability in homozygous females and hemizygous males. XO males are inviable. The inviability of these males is partially covered by Y fragments. With respect to viability, the fragments show similar regional differences in effectiveness as in the modification of the mottled phenotype.There is also a parental effect on the modulation of the white-mottled-2 phenotype.There is no correlation between the activity of Y chromosomal factors on spermiogenesis and the activity of Y factors on the modification of the variegation position effect. Suppression of Y chromosomal sites which normally unfold lampbrush loops during the spermatocyte stage and whose activity has previously been shown to be indispensible for normal differentiation of the male germ line cells does not result in any visible alterations of the effectiveness on the mottling. So there is obviously independence between these two different genetic activities of Y chromosomal factors. 相似文献
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Background
Introductions of non-native tiger salamanders into the range of California tiger salamanders have provided a rare opportunity to study the early stages of secondary contact and hybridization. We produced first- and second-generation hybrid salamanders in the lab and measured viability among these early-generation hybrid crosses to determine the strength of the initial barrier to gene exchange. We also created contemporary-generation hybrids in the lab and evaluated the extent to which selection has affected fitness over approximately 20 generations of admixture. Additionally, we examined the inheritance of quantitative phenotypic variation to better understand how evolution has progressed since secondary contact. 相似文献6.
The intellectual property rights debate focuses on the flow of germplasm from developing tropical countries to developed temperate nations. Few investigators have addressed the converse. We discuss the abundance and importance of introduced plants in pharmacopoeias of northern South America. Introduced species commonly are employed as medicines throughout the region and include at least 216 Eurasian, North American, African, and Pacific species. Among the Shuar of lowland Ecuador, four introduced plants (Citrus aurantium, Cymbopogon citratus, Saccharum officinarum, and Zingiber officinale) are included in their most commonly prescribed remedies. The widespread use of introduced plants is due, in part, to the medicinal value of plants whose primary use is for food (e.g., Musa X paradisiacal Similarly, many introduced ornamentals also have therapeutic value (e.g., Hedychium coronarium). Other species have been introduced specifically as medicines (e.g., Aloe vera). Restrictions on the flow of germplasm and plant knowledge may protect the economic interests of governments and national industry. If applied bilaterally, however, constraints on the movement of plants will limit the continued evolution of traditional medicinal systems in areas where they are most needed. 相似文献
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A newly developed computer model is used to predict the aqueous salt solution concentration, breathing pattern, and inhaled droplet size distribution parameters that will maximize pulmonary deposition of hygroscopic medicinal aerosols. The parameter values providing maximum pulmonary deposition include 1) a NaCl concentration in the aerosolized solution of 0.035 g/ml or higher if the subject can tolerate it, 2) as nearly a monodispersed inhaled aerosol size distribution as possible, 3) an aerosol mass median diameter of 2-3 micron, and 4) slow (7 breaths/min) uninterrupted breathing of 1.5-2 liters of aerosol/breath. With these values, the model predicts that pulmonary deposition can be increased by greater than 100% relative to the deposition achieved in conventional inhalation therapy with isotonic saline-based medications. 相似文献
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It has long been debated whether the mind consists of specialized and independently evolving modules, or whether and to what extent a general factor accounts for the variance in performance across different cognitive domains. In this study, we used a hierarchical Bayesian model to re-analyse individual level data collected on seven primate species (chimpanzees, bonobos, orangutans, gorillas, spider monkeys, brown capuchin monkeys and long-tailed macaques) across 17 tasks within four domains (inhibition, memory, transposition and support). Our modelling approach evidenced the existence of both a domain-specific factor and a species factor, each accounting for the same amount (17%) of the observed variance. In contrast, inter-individual differences played a minimal role. These results support the hypothesis that the mind of primates is (at least partially) modular, with domain-specific cognitive skills undergoing different evolutionary pressures in different species in response to specific ecological and social demands. 相似文献