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Andrew J. Prendergast 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2015,370(1671)
Malnutrition contributes to an estimated 45% of deaths among children under 5 years of age in developing countries, predominantly due to infections. Malnourished children therefore stand to benefit hugely from vaccination, but malnutrition has been described as the most common immunodeficiency globally, suggesting that they may not be able to respond effectively to vaccines. The immunology of malnutrition remains poorly characterized, but is associated with impairments in mucosal barrier integrity, and innate and adaptive immune dysfunction. Despite this, the majority of malnourished children can mount a protective immune response following vaccination, although the timing, quality and duration of responses may be impaired. This paper reviews the evidence for vaccine immunogenicity in malnourished children, discusses the importance of vaccination in prevention of malnutrition and highlights evidence gaps in our current knowledge. 相似文献
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The design, synthesis, and characterization of tight-binding inhibitors of calmodulin 总被引:5,自引:0,他引:5
Based on a consideration of the probable structure of calmodulin and some natural peptides known to interact with it, two calmodulin-binding peptides were designed. These peptides bind to calmodulin in helical conformations and are capable of forming electrostatic and hydrophobic interactions with calmodulin. Their dissociation constants for binding (less than or equal to 210 and 400 pM) place them as the tightest-binding inhibitors of calmodulin thus far reported. The study of the interactions of these and similar peptides with calmodulin will provide valuable insights into the mechanisms whereby calmodulin binds to target enzymes, and it also serves as an excellent model system for exploring the physical chemistry of protein-protein interaction. 相似文献
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M C Moncrieffe S Eaton Z Bajzer C Haydock J D Potter T M Laue F G Prendergast 《The Journal of biological chemistry》1999,274(25):17464-17470
Time resolved fluorescence anisotropy and sedimentation velocity has been used to study the rotational and translational hydrodynamic behavior of two mutants of chicken skeletal troponin C bearing a single tryptophan residue at position 78 or 154 in the metal-free-, metal-bound-, and troponin I peptide (residues 96-116 of troponin I)-ligated states. The fluorescence anisotropy data of both mutants were adequately described by two rotational correlation times, and these are compared with the theoretically expected values based on the rotational diffusion of an idealized dumbbell. These data imply that the motion of the N- and C-terminal domains of troponin C are independent. They also suggest that in the metal-free, calcium-saturated and calcium-saturated troponin I peptide-bound states, troponin C is elongated, having an axial ratio of 4-5. Calcium or magnesium binding to the high affinity sites alone reduces the axial ratio to approximately 3. However, with calcium bound to sites III and IV and in the presence of a 1:1 molar ratio of the troponin I peptide, troponin C is approximately spherical. The metal ion and troponin I peptide-induced length changes in troponin C may play a role in the mechanism by which the regulatory function of troponin C is effected. 相似文献
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