Modulation of the antagonistic properties of an insulin mimetic peptide by disulfide bridge modifications.

Insulin is a peptide responsible for regulating the metabolic homeostasis of the organism; it elicits its effects through binding to the transmembrane insulin receptor (IR). Insulin mimetics with agonistic or antagonistic effects toward the receptor are an exciting field of research and could find applications in treating diabetes or malignant diseases. We prepared five variants of a previously reported 20-amino acid insulin-mimicking peptide. These peptides differ from each other by the structure of the covalent bridge connecting positions 11 and 18. In addition to the peptide with a disulfide bridge, a derivative with a dicarba bridge and three derivatives with a 1,2,3-triazole differing from each other by the presence of sulfur or oxygen in their staples were prepared. The strongest binding to IR was exhibited by the peptide with a disulfide bridge. All other derivatives only weakly bound to IR, and a relationship between increasing bridge length and lower binding affinity can be inferred. Despite their nanomolar affinities, none of the prepared peptide mimetics was able to activate the insulin receptor even at high concentrations, but all mimetics were able to inhibit insulin-induced receptor activation. However, the receptor remained approximately 30% active even at the highest concentration of the agents; thus, the agents behave as partial antagonists. An interesting observation is that these mimetic peptides do not antagonize insulin action in proportion to their binding affinities. The compounds characterized in this study show that it is possible to modulate the functional properties of insulin receptor peptide ligands using disulfide mimetics.

Impact of mandatory microchipping on traceability of sheltered dogs in the Czech Republic.

Records of 4,455 sheltered dogs were analyzed to compare the numbers of traceable (able to be reunited with original caregivers) and untraceable (unable to be reunited with original caregivers) dogs before (Period 1) and after (Period 2) introduction of a mandatory microchipping. Records were also used to compare the numbers of microchipped dogs, to compare dogs' reunification with caregivers, and to estimate possible financial savings. In Period 1, 51.8% of the dogs were untraceable (median length of stay = 14 days) and 48.2% were traceable (median length of stay = 1 day). Of all traceable dogs, 24.5% were microchipped, and 67.5% of microchipped dogs were traceable. In Period 2, 57.1% of dogs were traceable (median length of stay = 0 days), and 42.9% were untraceable (median length of stay = 12 days). Of all traceable dogs, 61.4% had a microchip, and 80% of microchipped dogs were traceable. In Period 2, authorities saved more than US$43,400 on unreclaimed dog care. Mandatory microchipping of dogs appears to be an effective measure to increase reunification of sheltered dogs, decrease length of stay, and save authority funds.

Breed Characteristics of Abandoned and Lost Dogs in the Czech Republic.

Records on sheltered dogs were collected from 3 municipal dog shelters situated in different regions of the Czech Republic from 2010 to 2013. A total of 3,875 dogs were analyzed in this study. Among these, 1,614 dogs were subsequently reclaimed (lost dogs) and 2,261 dogs were abandoned and offered for adoption. The ratio of purebred dogs and crossbred dogs differed significantly when comparing lost (66.4% vs. 33.6%) and abandoned dogs (35.0% vs. 65.0%). The median time until lost dogs were reclaimed was 1 day, and it was not affected by purebred status. The median time until abandoned dogs were adopted was 23 days. In abandoned dogs, purebred status had a significant effect on the time the dog spent at the shelter before adoption. The median time until adoption for crossbred dogs was 27 days, whereas the median time until adoption for purebred dogs was 19 days. The breed group influenced the length of stay (LOS) in abandoned dogs. Small companion dogs had the shortest LOS (median = 15 days) and guard dogs had the longest LOS (median = 25 days).

Dioecious Silene latifolia plants show sexual dimorphism in the vegetative stage.

BACKGROUND: Prior to this study, no differences in gene expression between male and female dioecious plants in the vegetative state had been detected. Among dioecious plants displaying sexual dimorphism, Silene latifolia is one of the most studied species. Although many sexually dimorphic traits have been described in S. latifolia, all of them are quantitative, and they usually become apparent only after the initiation of flowering. RESULTS: We present RT-PCR-based evidence that in S. latifolia, sexual dimorphism in gene expression is present long before the initiation of flowering. We describe three ESTs that show sex-specific (two male specific and one female specific) transcription at the rosette stage before the first flowering season. CONCLUSIONS: To our knowledge, this study provides the first molecular evidence of early pre-flowering sexual dimorphism in angiosperms.