North American Propolis Extracts From Upstate New York Decrease Nosema ceranae (Microsporidia) Spore Levels in Honey Bees (Apis mellifera).

Nosema ceranae infections in honey bees (Apis mellifera) pose a severe threat to colony health. Beekeepers have used dicyclohexylammonium fumagillin to control Nosema apis, although it may be ineffective against N. ceranae. We investigated the ability of various propolis extracts collected from Upstate New York (United States) to decrease in vivo N. ceranae infection levels when fed ad libitum to N. ceranae-infected honey bees. Propolis extracts, most notably a dichloromethane extract, significantly lowered spore levels in a dose-dependent fashion 4 days post inoculation. When testing the in vitro anti-Nosema activity of propolis extracts, we report for the first time that spore viability was unaffected after a 24 h exposure to propolis extracts. These results present evidence that propolis extracts may effectively lower Microsporidia infections in honey bees, and that direct exposure of environmental spores to propolis alone does not kill N. ceranae.

Complementary Effects of Host Defense Peptides Piscidin 1 and Piscidin 3 on DNA and Lipid Membranes: Biophysical Insights into Contrasting Biological Activities.

Piscidins were the first antimicrobial peptides discovered in the mast cells of vertebrates. While two family members, piscidin 1 (p1) and piscidin 3 (p3), have highly similar sequences and α-helical structures when bound to model membranes, p1 generally exhibits stronger antimicrobial and hemolytic activity than p3 for reasons that remain elusive. In this study, we combine activity assays and biophysical methods to investigate the mechanisms underlying the cellular function and differing biological potencies of these peptides, and report findings spanning three major facets. First, added to Gram-positive (Bacillus megaterium) and Gram-negative (Escherichia coli) bacteria at sublethal concentrations and imaged by confocal microscopy, both p1 and p3 translocate across cell membranes and colocalize with nucleoids. In E. coli, translocation is accompanied by nonlethal permeabilization that features more pronounced leakage for p1. Second, p1 is also more disruptive than p3 to bacterial model membranes, as quantified by a dye-leakage assay and (2)H solid-state NMR-monitored lipid acyl chain order parameters. Oriented CD studies in the same bilayers show that, beyond a critical peptide concentration, both peptides transition from a surface-bound state to a tilted orientation. Third, gel retardation experiments and CD-monitored titrations on isolated DNA demonstrate that both peptides bind DNA but p3 has stronger condensing effects. Notably, solid-state NMR reveals that the peptides are α-helical when bound to DNA. Overall, these studies identify two polyreactive piscidin isoforms that bind phosphate-containing targets in a poised amphipathic α-helical conformation, disrupt bacterial membranes, and access the intracellular constituents of target cells. Remarkably, the two isoforms have complementary effects; p1 is more membrane active, while p3 has stronger DNA-condensing effects. Subtle differences in their physicochemical properties are highlighted to help explain their contrasting activities.

Division of labor in the honey bee (Apis mellifera): the role of tyramine beta-hydroxylase.

The biogenic amine octopamine (OA) is involved in the regulation of honey bee behavioral development; brain levels are higher in foragers than bees working in the hive, especially in the antennal lobes, and treatment causes precocious foraging. We measured brain mRNA and protein activity of tyramine beta-hydroxylase (T betah), an enzyme vital for OA synthesis, in order to begin testing the hypothesis that this enzyme is responsible for the rising levels of OA during honey bee behavioral development. Brain OA levels were greater in forager bees than in bees engaged in brood care, as in previous studies, but T betah activity was not correlated with bee behavior. T betah mRNA levels, however, did closely track OA levels during behavioral development, and T betah mRNA was localized to previously identified octopaminergic neurons in the bee brain. Our results show that the transcription of this neurotransmitter synthetic enzyme is associated with regulation of social behavior in honey bees, but other factors may be involved.

Abeta1-15 is less immunogenic than Abeta1-40/42 for intranasal immunization of wild-type mice but may be effective for "boosting".

Immunizing mouse models of Alzheimer's disease (AD) against beta-amyloid (Abeta) leads to a decrease in cerebral Abeta burden as well as an improvement in behavioral deficits. Circulating Abeta-antibodies may be responsible for interfering with Abeta deposition. In the present study, we attempted to initiate more robust antibody production in wild type (WT) mice. Three immunization strategies were examined: intranasal (i.n.) immunization with Abetal-15 or full-length Abeta1-40/42, i.n. administration of Abeta combined with mucosal adjuvants, native labile enterotoxin (LT) or its non-toxic form, LT(R192G), and prime-boost regimes. Using Abeta1-15 as the primary immunogen for intranasal immunization did not initiate strong antibody production. When Abeta1-15 or Abeta1-40/42 was combined with native LT or LT(R192G), antibody production was significantly increased. Nasal immunization with Abeta1-15 and native LT successfully "boosted" an immune response "primed" by an intraperitoneal (i.p.) injection of Abeta1-40/42, producing moderately high Abeta titers that remained stable for at least 6 months. Serum anti-Abeta antibodies, regardless of the length of the Abeta immunogen, consistently detected human AD plaques, had epitopes within Abeta1-15, and were predominantly of the IgG2b, IgG1, and IgG2a isotypes. The adjuvants were well-tolerated in the mice. Thus, Abeta1-15 may have potential as a safer, more cost-effective "boosting" immunogen than the full-length Abeta peptide for chronic, active Abeta immunization.