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Avidin molecules in which a fraction of the four binding sites were occupied by biotin did not dissociate completely in 6.4m-guanidinium chloride. Only unoccupied subunits dissociated. The remainder recombined to form the tetrameric avidin-biotin complex. The rate at which unoccupied subunits were unfolded and dissociated was only decreased by one-half in species in which three of the four binding sites were occupied by biotin. These results can be explained by assuming that unfolding of unoccupied subunits followed by dissociation from the tetramer is initiated by penetration of guanidinium ions into the binding site and disorganization of this region of the subunit. When a site is occupied by biotin this pathway is blocked and the subunit does not unfold. Each subunit behaves independently and is not markedly stabilized when neighbouring subunits are occupied.  相似文献   
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The roles of the Notch pathway proteins in normal adult vascular physiology and the pathogenesis of brain arteriovenous malformations are not well‐understood. Notch 1 and 4 have been detected in human and mutant mice vascular malformations respectively. Although mutations in the human Notch 3 gene caused a genetic form of vascular stroke and dementia, its role in arteriovenous malformations development has been unknown. In this study, we performed immunohistochemistry screening on tissue microarrays containing eight surgically resected human brain arteriovenous malformations and 10 control surgical epilepsy samples. The tissue microarrays were evaluated for Notch 1–4 expression. We have found that compared to normal brain vascular tissue Notch‐3 was dramatically increased in brain arteriovenous malformations. Similarly, Notch 4 labelling was also increased in vascular malformations and was confirmed by western blot analysis. Notch 2 was not detectable in any of the human vessels analysed. Using both immunohistochemistry on microarrays and western blot analysis, we have found that Notch‐1 expression was detectable in control vessels, and discovered a significant decrease of Notch 1 expression in vascular malformations. We have demonstrated that Notch 3 and 4, and not Notch 1, were highly increased in human arteriovenous malformations. Our findings suggested that Notch 4, and more importantly, Notch 3, may play a role in the development and pathobiology of human arteriovenous malformations.  相似文献   
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Despite concern expressed two decades ago, there has been little recent discussion about continuing declines of migrant bird populations. Monitoring efforts have been focused almost exclusively on the breeding grounds. We describe the long-term decline of a winter-resident bird population in Guánica Commonwealth Forest, Puerto Rico, one of the last remaining tracts of high-quality tropical dry forests in the Caribbean. The winter bird community has exhibited dramatic declines, with constant-effort mist netting now capturing about one-third as many birds as it did 20 years ago. Population estimates for the three most common species have declined dramatically, even though survival rates have remained constant, and other species are now virtually absent from a site where they once were fairly common. Although explanations for these declines are speculative, particularly because they involve multiple species, we argue that the strength and duration of these declines in well-preserved dry forest within a biosphere reserve should stimulate renewed discussion of migrant population trends and comparison with other recent monitoring activities.  相似文献   
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The cobalamin-dependent cytosolic enzyme, methionine synthase (EC.2.1.1.13), catalyzes the remethylation of homocysteine to methionine using 5-methyltetrahydrofolate as the methyl donor. The products of this remethylation--methionine and tetrahydrofolate--participate in the active methionine and folate pathways. Impaired methionine synthase activity has been implicated in the pathogenesis of anaemias, cancer and neurological disorders. Although the need for potent and specific inhibitors of methionine synthase has been recognized, there is a lack of such agents. In this study, we designed, synthesized and evaluated the inhibitory activity of a series of substituted benzimidazoles and small benzothiadiazoles. Kinetic analysis revealed that the benzimidazoles act as competitive inhibitors of the rat liver methionine synthase, whilst the most active benzothiadiazole (IC(50) = 80 microm) exhibited characteristics of uncompetitive inhibition. A model of the methyltetrahydrofolate-binding site of the rat liver methionine synthase was constructed; docking experiments were designed to elucidate, in greater detail, the binding mode and reveal structural requirements for the design of inhibitors of methionine synthase. Our results indicate that the potency of the tested compounds is related to a planar region of the inhibitor that can be positioned in the centre of the active site, the presence of a nitro functional group and two or three probable hydrogen-bonding interactions.  相似文献   
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The pattern of breast-feeding in 127 infants admitted to hospital with respiratory syncytial virus infection was compared with that in 503 age-matched controls. Thirty per cent of children with infection had been breast-fed compared with 49% of controls. The approximate relative risk of being admitted to hospital with respiratory syncytial virus infection if not breast-fed was 2.2. Several other factors were also considered, including an assessment of maternal care and home environment; the mother''s age, marital state, and smoking habits; the number of siblings; and gestation. Adverse factors were all associated with an increased risk of admission with infection, but breast-feeding still appeared to provide protection after controlling for these other factors in turn. These findings provide further support for encouraging mothers to breast-feed their infants and should prompt further studies into the immune status of mothers and into the nature of the protective factors in their breast milk.  相似文献   
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Intraspecific aggression is known to be an important behavior structuring bird communities, but interspecific aggression has been studied less frequently. Because of a high degree of similarity in foraging niches, I hypothesized that American redstarts (Setophaga ruticilla) and Adelaide's warblers (S. adelaidae) would interact aggressively during the non‐breeding season in southwest Puerto Rico. I used a crossover experiment to determine whether these species were aggressive to heterospecifics, presenting decoys and vocalizations of these two species, along with a control, to individuals and observing their vocal and physical responses. However, the study used only a single playback and decoy for each species, limiting the generality of the conclusions. Both species responded aggressively to decoys of conspecifics and heterospecifics, while no individual responded to the control. Responses to conspecifics were stronger than responses to heterospecifics as hypothesized, although the differences were significant only in Adelaide's warblers. The interspecific aggression observed in this study, combined with previous studies showing a high degree of overlap in space use and foraging niches and probable food limitation, strongly suggests that these species are competing for food during the non‐breeding season.  相似文献   
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