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The corticotropin-releasing factor (CRF) analog CRF 9-41 inhibits CRF, but not forskolin or dibutyryl cyclic AMP, stimulated release of ACTH from isolated pituitary cells. CRF 9-41 also blocks CRF-stimulated accumulation of cyclic AMP in a parallel dose dependent fashion. CRF 9-41 has no effect on basal ACTH release or cAMP levels. This substantiates that the analog acts as a direct CRF antagonist and that the site of this inhibition is most likely at the level of binding of CRF to its receptor on the corticotrope. Various substances, including most prominently glucocorticoids, inhibit release of ACTH from the pituitary. In an effort to develop another class of inhibitors, Rivier et al recently synthesized analogs of corticotropin releasing factor (CRF). One among these, alpha-helical ovine CRF 9-41 blunts adrenalectomy and stress induced ACTH release in non-anesthetized rats. At micromolar concentrations, CRF 9-41, shifts rightward the dose response of isolated pituitary cells to ovine CRF. Thus, the authors suggested that CRF 9-41 acts as a competitive antagonist to CRF-induced ACTH secretion. CRF appears to act through stimulation of adenylate cyclase. To determine the potential site of action of CRF 9-41 in the activation sequence for adenylate cyclase, we studied its effects on pituitary cyclic AMP formation and ACTH secretion from dispersed anterior pituitary cells derived from normal adult rats, as well as, its interaction with cyclic nucleotide agonists.  相似文献   
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Tracking 47 post-spawned adult Atlantic salmon Salmo salar L. in a hydropower-regulated river through autumn, winter and spring revealed that winter survival was 56% and 75% in two study years, respectively, with higher mortality of males than females (50% vs. 33% and 100% vs. 13%, respectively). Some kelts (n = 7) displayed nondirected movements that were interpreted as a reconditioning period for an average of 9–17 days prior to directed downstream movements indicating the initiation of migration. Survival after the initiation of migration in spring was 83% and 94% to the hydropower dam in the first and second study years, and decreased to 60 and 63%, respectively, after dam passage. There were no further losses in the downriver reach in the second year, with the first year having a cumulative survival estimate of 53% to the river mouth. Kelts approached the dam when the spillway gates were available as a passage option most of the time (64%–75%), but some kelts arrived at the dam or had not yet passed when spillways were closed (n = 6) and the only remaining passage option was restricted to the turbines. However, all but one kelt that must have passed via turbine were successful in reaching the river mouth. Migratory delay presumably due to searching behaviour caused by low water flow was estimated at approximately 6 days as migration rates were significantly slower in the reservoir (median ± s.e. 8.5 ± 2.5 km day−1) than up- (29.7 ± 5.0 km day−1) or downriver (22.1 ± 3.1 km day−1). The proportion of time (median 30%) that kelts spent swimming upstream (searching behaviour) in the reservoir was a significant variable for migration success.  相似文献   
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When the environment changes, sensory systems can adapt plastically or evolve genetically to the new surroundings, and traits and behaviours reliant on these sensory systems may also change, leading to altered evolutionary trajectories. We tested for differences in colour‐based foraging preferences of guppies (Poecilia reticulata) that lived for 6–10 generations under each of three light environments (green, lilac or control) to determine whether evolution under different light environments alters visually based behaviour. When tested in a common light environment, we found differences in pecking behaviour between treatments that were likely due to changes in the visual system. Pecking behaviour towards green stimuli was consistent across light treatments, possibly reflecting the importance of detecting green algae in the wild. The blue stimulus was only pecked at by fish from the control environments. Behaviour towards long wavelength stimuli varied, possibly due to the polymorphic nature of the long wavelength opsins. These results are consistent with one component of sensory drive but do not allow us to conclude whether these differences are due to plastic or evolved responses.  相似文献   
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In order to establish infection, pathogenic bacteria must obtain essential nutrients such as iron. Under acidic and/or anaerobic conditions, most bacteria utilize the Feo system in order to acquire ferrous iron (Fe2+) from their host environment. The mechanism of this process, including its regulation, remains poorly understood. In this work, we have determined the crystal structure of FeoA from the nosocomial agent Klebsiella pneumoniae (KpFeoA). Our structure reveals an SH3-like domain that mediates interactions between neighboring polypeptides via hydrophobic intercalations into a Leu-rich surface ridge. Using docking of a small peptide corresponding to a postulated FeoB partner binding site, we demonstrate that KpFeoA can assume both “open” and “closed” conformations, controlled by binding at this Leu-rich ridge. We propose a model in which a “C-shaped” clamp along the FeoA surface mediates interactions with its partner protein, FeoB. These findings are the first to demonstrate atomic-level details of FeoA-based protein-protein interactions and provide a framework for testing FeoA-FeoB interactions, which could be exploited for future antibiotic developments.  相似文献   
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Recent developments have led to advances in our understanding of the structure and mechanism of action of proton-translocating (or AB) transhydrogenase. There is (a) a high-resolution crystal structure, and an NMR structure, of the NADP(H)-binding component (dIII), (b) a homology-based model of the NAD(H)-binding component (dI) and (c) an emerging consensus on the position of the transmembrane helices (in dII). The crystal structure of dIII, in particular, provides new insights into the mechanism by which the energy released in proton translocation across the membrane is coupled to changes in the binding affinities of NADP(+) and NADPH that drive the chemical reaction.  相似文献   
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Animals frequently use signals that travel further than the spacing between individuals. For every intended recipient of a given signal there are likely to be many other individuals that receive information. Eavesdropping on signalling interactions between other individuals provides a relatively cost-free method of assessing future opponents or mates. Male great tits (Parus major) extract relative information from such interactions between individuals unknown to them. Here, we show that male great tits can take information gathering a stage further and obtain more information about a previously unencountered intruder, by the hitherto unknown capability of combining information gathered by eavesdropping with that derived from their own direct interaction with an individual. Prior experience with an intruder (A) was achieved by subjecting a focal male to different levels of intrusion simulated using interactive playback. This intruder (A) then took part in a simulated interaction with an unknown male (B) outside the territorial boundary of the focal males. In response to subsequent intrusion by the second male (B), focal males showed low song output in response to males that had lost to a male that the subject was able to beat. Males of known high quality, or those about which information was ambiguous, elicited a high level of song output by focal males. We discuss the implications of this finding for the evolution of communication and social behaviour.  相似文献   
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