Findings have provided critical direction for the continued development and sustainability of DRPHC efforts. Others could apply a similar evaluation to better understand factors that promote the development and maintenance of their coalitions.
There is high-demand for new methods to modify peptides, for application in drug discovery and biomedicine. A C-H functionalization protocol for the olefination of tryptophan residues in peptides is described. The modification is successful for Trp residues at any position in the peptide, has broad scope in the styrene coupling partner, and offers opportunities for conjugating peptides with other biomolecules. For peptides containing both Trp and Phe, directing group manipulation enables full-control of residue selectivity. Peptide modification has a critical role to play in drug discovery, the diagnosis of disease, and the understanding of biological mechanism and function. 1,2 As examples, peptidefluorophore conjugates, 3-5 which enable the imaging of biological systems, have been used to diagnose infection, 6,7 and to aid surgery. 8,9 In drug discovery, where peptide therapeutics often have higher potency and target specificity than small molecule drugs, 10-12 synthetic peptide modification can provide necessary improvements to drug stability, cell penetration and oral bioavailability. 13-16 Of the large number of methods that have been developed for the modification of peptides, 2,17 most rely upon the reactions of heteroatoms, which may themselves be crucial to structure and biological function. 18,19 Alternatively, peptides and proteins have been modified at carbon atoms by metalcatalyzed cross-coupling reactions, but these methods require the incorporation of non-natural amino acids. 20-22 Consequently, new methods of peptide modification that operate at carbon atoms and in native peptides are needed. To achieve this goal, there has been rapid progress in developing methods for the C-H functionalization of peptides. 23-37 For example, C(sp 3)-H functionalization of alanine residues can give rise to phenylalanine derivates. 25 C(sp 2)-H functionalization of aromatic amino acids has focussed almost entirely on tryptophan (Trp) residues, that have been modified using arylation, alkynylation and allylation, Scheme 1A. 26-35 In addition , the modification of phenylalanine (Phe) residues in peptides has recently been achieved through C-H olefination, Scheme 1B. 36-38 Scheme 1. C-H functionalization of aromatic amino acids in peptides.
IntroductionThe prevention and control of Actinobacillus pleuropneumoniae in commercial production settings is based on serological monitoring. Enzyme-linked immunosorbent assays (ELISAs) have been developed to detect specific antibodies against a variety of A. pleuropneumoniae antigens, including long-chain lipopolysaccharides (LPS) and the ApxIV toxin, a repeats-in-toxin (RTX) exotoxin unique to A. pleuropneumoniae and produced by all serovars. The objective of this study was to describe ApxIV antibody responses in serum and oral fluid of pigs.Material and MethodsFour groups of pigs (six pigs per group) were inoculated with A. pleuropneumoniae serovars 1, 5, 7, or 12. Weekly serum samples and daily oral fluid samples were collected from individual pigs for 56 days post inoculation (DPI) and tested by LPS and ApxIV ELISAs. The ApxIV ELISA was run in three formats to detect immunlgobulins M, G, and A (IgM, IgG and IgA) while the LPS ELISA detected only IgG.ResultsAll pigs inoculated with A. pleuropneumoniae serovars 1 and 7 were LPS ELISA serum antibody positive from DPI 14 to 56. A transient and weak LPS ELISA antibody response was observed in pigs inoculated with serovar 5 and a single antibody positive pig was observed in serovar 12 at ≥35 DPI. Notably, ApxIV serum and oral fluid antibody responses in pig inoculated with serovars 1 and 7 reflected the patterns observed for LPS antibody, albeit with a 14 to 21 day delay.ConclusionThis work suggests that ELISAs based on ApxIV antibody detection in oral fluid samples could be effective in population monitoring for A. pleuropneumoniae.
Children’s narrative abilities in the preschool years have been found to predict their later literacy skills. Mothers’ verbalizations during shared personal narratives with their preschoolers have been shown to facilitate children’s development of narrative skills. The present study sought to extend the literature by investigating mothers’ use of two types of questions (information requests, ‘yes/no’ questions) and two types of confirmation (praise, repetition of child content) when discussing past events with their preschoolers, as a function of child age and gender. Study participants were 32 American mothers and their preschoolers, who were either 3 years of age or 5 years of age. Mother–preschooler dyads were audiotaped discussing three past events which they had shared. Results indicated that mothers provided significantly more information requests and repetition of child content when co-constructing narratives with 3-year-olds than with 5-year-olds. Overall, the results are consistent with the literature regarding parental sensitivity to children’s specific needs for task assistance in the early childhood period.
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