Tests of four baits for oral vaccination of dogs against rabies in Tunisia.
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Biomedical subjects
Publications and source records attributed to H Matter.
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One carbonyl oxygen of the cyclic hexapeptide cyclo(-Gly1-Pro2-Phe3-Val4-Phe5-Phe6-) (A) can be selectively exchanged with sulphur using Yokoyama's reagent. Surprisingly it was not the C=] of Gly1 but that of Phe5 which was substituted and cyclo(-Gly1-Pro2-Phe3-Val4-Phe5 psi [CS-NH]Phe6-) (B) was obtained. Thionation results in a conformational change of the peptide backbone although the C=O of Phe5 and the corresponding C=S are not involved in internal hydrogen bonds. Two isomers in slow exchange, containing a cis Gly1-Pro2 bond in a beta VIa-turn (minor) and a trans Gly-Pro bond in a beta II'-turn (major), were analyzed by restrained molecular dynamics in vacuo and in DMSO as well as using time dependent distance constraints. It is impossible to fit all experimental data to a static structure of each isomer. Interpreting the conflicting NOEs, local segment flexibility is found. MD simulations lead to a dynamic model for each structure with evidence of an equilibrium between a beta I- and beta II-turn about the Val4-Phe5 amide bond in both the cis and trans isomers. Additionally proton relaxation rates in the rotating frame (R1 rho) were measured to verify the assumption of this fast beta I/beta II equilibrium within each isomer. Significant contributions to R1 rho-rates from intramolecular motions were found for both isomers. Therefore it is possible to distinguish between at least four conformers interconverting on different time scales based on NMR data and MD refinement. This work shows that thionation is a useful modification of peptides for conformation-activity investigations.
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Dog populations, like other populations, depend on the availability of resources (food, water, and shelter). Humans either make available or deliberately withhold resources for varying proportions of dog populations. Dog-keeping practices and the duties of responsible ownership vary with the cultural setting. Dog populations often attain densities that allow the species to be a main host of rabies. The epidemiology of dog rabies is not well understood, despite the easy access to dog populations. Today dog rabies is predominant in developing countries. In addition to the high rate of exposure of humans to dogs, traditional medical beliefs and practices are the most important cultural factors that lead to high numbers of cases of human rabies. Dog rabies control programs have been successful in the past, but most are failing today. Program development should follow managerial principles and take into consideration the biology of dog populations as well as cultural constraints. Elimination of stray dogs is not an efficient means of controlling either the dog population or rabies, but it may create public awareness.