Replicating rather than nonreplicating adenovirus-human immunodeficiency virus recombinant vaccines are better at eliciting potent cellular immunity and priming high-titer antibodies

A major challenge in combating the human immunodeficiency virus (HIV) epidemic is the development of vaccines capable of inducing potent, persistent cellular immunity and broadly reactive neutralizing antibody responses to HIV type 1 (HIV-1). We report here the results of a preclinical trial using the chimpanzee model to investigate a combination vaccine strategy involving sequential priming immunizations with different serotypes of adenovirus (Ad)/HIV-1(MN)env/rev recombinants and boosting with an HIV envelope subunit protein, oligomeric HIV(SF162) gp140deltaV2. The immunogenicities of replicating and nonreplicating Ad/HIV-1(MN)env/rev recombinants were compared. Replicating Ad/HIV recombinants were better at eliciting HIV-specific cellular immune responses and better at priming humoral immunity against HIV than nonreplicating Ad-HIV recombinants carrying the same gene insert. Enhanced cellular immunity was manifested by a greater frequency of HIV envelope-specific gamma interferon-secreting peripheral blood lymphocytes and better priming of T-cell proliferative responses. Enhanced humoral immunity was seen in higher anti-envelope binding and neutralizing antibody titers and better induction of antibody-dependent cellular cytotoxicity. More animals primed with replicating Ad recombinants mounted neutralizing antibodies against heterologous R5 viruses after one or two booster immunizations with the mismatched oligomeric HIV-1(SF162) gp140deltaV2 protein. These results support continued development of the replicating Ad-HIV recombinant vaccine approach and suggest that the use of replicating vectors for other vaccines may prove fruitful.     

Enhancement of YD spin relaxation by the CaMn4 cluster in photosystem II detected at room temperature: A new probe for the S-cycle

The long-lived, light-induced radical Y_D^• of the Tyr161 residue in the D2 protein of Photosystem II (PSII) is known to magnetically interact with the CaMn₄ cluster, situated ∼ 30 Å away. In this study we report a transient step-change increase in Y_D^• EPR intensity upon the application of a single laser flash to S₁ state-synchronised PSII-enriched membranes from spinach. This transient effect was observed at room temperature and high applied microwave power (100 mW) in samples containing PpBQ, as well as those containing DCMU. The subsequent decay lifetimes were found to differ depending on the additive used. We propose that this flash-induced signal increase was caused by enhanced spin relaxation of Y_D^• by the OEC in the S₂ state, as a consequence of the single laser flash turnover. The post-flash decay reflected S₂ → S₁ back-turnover, as confirmed by their correlations with independent measurements of S₂ multiline EPR signal and flash-induced variable fluorescence decay kinetics under corresponding experimental conditions. This flash-induced effect opens up the possibility to study the kinetic behaviour of S-state transitions at room temperature using Y_D^• as a probe.     

Hindlimb muscle fiber types in two frogs (Rana catesbeiana and Litoria caerulea) with different locomotor behaviors: histochemical and enzymatic comparison

To test how differences in locomotor behaviors may be reflected in muscle fiber-type diversity within anurans, a comparison of hindlimb muscles between the powerful terrestrial hopper, Rana catesbeiana, and the tree frog, Litoria caerulea, was done. One postural muscle (tibialis posticus, TP) and one primary hopping muscle (plantaris longus, PL), were characterized to identify muscle fiber types using standard histochemical methods. In addition, spectophotometric analysis of activity levels of the oxidative enzyme citrate synthase (CS) and the glycolytic enzyme lactate dehydrogenase (LDH) were done in each muscle. In spite of presumed differences in behavior between the species, we found no significant differences in the proportions of the identified fiber types when the muscles were compared across species. In addition, there were no significant differences in the proportions of the different fiber types between the postural versus phasic muscles within species. Within Rana, the postural muscle (TP) had greater oxidative capacity (as measured by CS activity) than did the phasic muscle (PL). Both muscles had equivalent LDH activities. Within Litoria, PL and TP did not differ in either LDH or CS activities. Both PL and TP of Litoria had less LDH activity and greater CS activity than their homologs in Rana. Thus, in spite of the uniform populations of fiber types between muscles and species, the metabolic diversity based on enzyme activity is consistent with behavioral differences between the species. These results suggest that the range of functional diversity within fiber types may be very broad in anurans, and histochemical fiber typing alone is not a clear indicator of their metabolic or functional properties.     

Using persuasive messages to encourage hunters to support regulation of lead shot

Lead shot from hunting adds the toxic metal to environments worldwide. The United States banned lead shot for hunting waterfowl in 1991 and 26 states have lead shot restrictions beyond those mandated for waterfowl hunting. The Minnesota Department of Natural Resources (MDNR) was interested in studying hunter attitudes about expanded restrictions on the use of lead shot for hunting small game to understand what communication strategies might increase public support for potential restrictions on lead shot. We mailed messages about lead shot, including 1,200 control messages and 400 of each of 9 treatment messages, and surveys to 4,800 resident small game hunters. We compared attitudes and intentions related to a possible ban among control and treatment groups. Compared to the control message, all treatment messages elicited more positive attitudes and intentions to support a ban. A basic factual message, messages with references to Ducks Unlimited, and a first-person narrative message generated the strongest support for a ban. Results also demonstrated a substantial relationship between the use of lead shot and response to persuasive messages supporting a ban. © 2012 The Wildlife Society.     

Relationship between a Common Variant in the Fatty Acid Desaturase (FADS) Cluster and Eicosanoid Generation in Humans

Dramatic shifts in the Western diet have led to a marked increase in the dietary intake of the n-6 polyunsaturated fatty acid (PUFA), linoleic acid (LA). Dietary LA can then be converted to arachidonic acid (ARA) utilizing three enzymatic steps. Two of these steps are encoded for by the fatty acid desaturase (FADS) cluster (chromosome 11, 11q12.2-q13) and certain genetic variants within the cluster are highly associated with ARA levels. However, no study to date has examined whether these variants further influence pro-inflammatory, cyclooxygenase and lipoxygenase eicosanoid products. This study examined the impact of a highly influential FADS SNP, rs174537 on leukotriene, HETE, prostaglandin, and thromboxane biosynthesis in stimulated whole blood. Thirty subjects were genotyped at rs174537 (GG, n = 11; GT, n = 13; TT, n = 6), a panel of fatty acids from whole serum was analyzed, and precursor-to-product PUFA ratios were calculated as a marker of the capacity of tissues (particularly the liver) to synthesize long chain PUFAs. Eicosanoids produced by stimulated human blood were measured by LC-MS/MS. We observed an association between rs174537 and the ratio of ARA/LA, leukotriene B₄, and 5-HETE but no effect on levels of cyclooxygenase products. Our results suggest that variation at rs174537 not only impacts the synthesis of ARA but the overall capacity of whole blood to synthesize 5-lipoxygenase products; these genotype-related changes in eicosanoid levels could have important implications in a variety of inflammatory diseases.     

PLANTING DENSITY INFLUENCES THE EXPRESSION OF GENETIC VARIATION IN SEED MASS IN WILD RADISH (RAPHANUS SATIVUS L.: BRASSICACEAE)

To determine the effects of density, genotype, and their interaction on individual seed mass in Raphanus sativus L., we replicated maternal and paternal families of seed across two planting densities in an experimental garden. Seeds were produced by a nested breeding design performed in the greenhouse. Among garden-raised plants, density had a strong negative effect on the mass of seeds produced. At low density, the identity of the greenhouse-grown maternal plants had a strong effect on F₂ seed mass, while in high-density plots, there were no significant parental effects on mean seed mass. Significant parental genotype density interactions contributed to variation in F₂ seed mass. Norms of reaction for each of the 15 paternal sibships illustrate paternal family density interactions. Three sibships exhibited significant declines in mean seed mass with increasing density; 12 sibships showed no change. Maternal family density interaction effects on seed mass were also detected; among maternal sibships, mean seed mass at low density was negatively correlated with mean seed mass at high density. These results demonstrate: a) planting density has a strong effect on mean individual seed mass produced by adults; b) density influences the magnitude of maternal effects on progeny phenotype; and c) genotype density interactions influence seed mass, potentially contributing to the maintenance of maternal genetic variation in seed mass in natural populations of wild radish.