Leisure‐Time Physical Activity and Reduced Plasma Levels of Obesity‐Related Inflammatory Markers

Objective: This study investigated the relationship between physical activity and the obesity‐related inflammatory markers C‐reactive protein, interleukin‐6, and soluble tumor necrosis factor receptors (sTNF‐Rs) 1 and 2. Furthermore, we examined the relationship between physical activity and insulin sensitivity (insulin, C‐peptide, and hemoglobin A_1c levels) and whether inflammatory markers mediate this association. Research Methods and Procedures: Biomarkers were measured in 405 healthy men and 454 healthy women from two large ongoing prospective studies. Information about physical activity and other variables was assessed by questionnaires. Results: After adjustment for other predictors of inflammation, physical activity was inversely associated with plasma levels of sTNF‐R1, sTNF‐R2, interleukin‐6, and C‐reactive protein (p = 0.07, p = 0.004, p = 0.04, and p = 0.009). After further adjustment for BMI and leptin, as a surrogate for fat mass, most of these associations were no longer significant. Physical activity was also inversely related to insulin and C‐peptide levels (p = 0.008 and p < 0.001); however, in contrast to BMI and leptin, levels of inflammatory markers explained only very little of this inverse relationship. Discussion: These results suggest that frequent physical activity is associated with lower systemic inflammation and improved insulin sensitivity. These associations can partially be explained by a lower degree of obesity in physically active subjects. Although inflammatory markers may mediate obesity‐dependent effects of physical activity on inflammatory related diseases such as type 2 diabetes or coronary heart disease, our study suggests that they do not directly account for the beneficial effects of physical activity on insulin resistance.     

Gene-environment interaction in the onset of eczema in infancy: filaggrin loss-of-function mutations enhanced by neonatal cat exposure

Background

Loss-of-function variants in the gene encoding filaggrin (FLG) are major determinants of eczema. We hypothesized that weakening of the physical barrier in FLG-deficient individuals may potentiate the effect of environmental exposures. Therefore, we investigated whether there is an interaction between FLG loss-of-function mutations with environmental exposures (pets and dust mites) in relation to the development of eczema.

Methods and Findings

We used data obtained in early life in a high-risk birth cohort in Denmark and replicated the findings in an unselected birth cohort in the United Kingdom. Primary outcome was age of onset of eczema; environmental exposures included pet ownership and mite and pet allergen levels. In Copenhagen (n = 379), FLG mutation increased the risk of eczema during the first year of life (hazard ratio [HR] 2.26, 95% confidence interval [CI] 1.27–4.00, p = 0.005), with a further increase in risk related to cat exposure at birth amongst children with FLG mutation (HR 11.11, 95% CI 3.79–32.60, p < 0.0001); dog exposure was moderately protective (HR 0.49, 95% CI 0.24–1.01, p = 0.05), but not related to FLG genotype. In Manchester (n = 503) an independent and significant association of the development of eczema by age 12 mo with FLG genotype was confirmed (HR 1.95, 95% CI 1.13–3.36, p = 0.02). In addition, the risk increased because of the interaction of cat ownership at birth and FLG genotype (HR 3.82, 95% CI 1.35–10.81, p = 0.01), with no significant effect of the interaction with dog ownership (HR 0.59, 95% CI 0.16–2.20, p = 0.43). Mite-allergen had no effects in either cohort. The observed effects were independent of sensitisation.

Conclusions

We have demonstrated a significant interaction between FLG loss-of-function main mutations (501x and 2282del4) and cat ownership at birth on the development of early-life eczema in two independent birth cohorts. Our data suggest that cat but not dog ownership substantially increases the risk of eczema within the first year of life in children with FLG loss-of-function variants, but not amongst those without. FLG-deficient individuals may need to avoid cats but not dogs in early life.     

Combined prime-boost vaccination against tick-borne encephalitis (TBE) using a recombinant vaccinia virus and a bacterial plasmid both expressing TBE virus non-structural NS1 protein

Background  

Heterologous prime-boost immunization protocols using different gene expression systems have proven to be successful tools in protecting against various diseases in experimental animal models. The main reason for using this approach is to exploit the ability of expression cassettes to prime or boost the immune system in different ways during vaccination procedures. The purpose of the project was to study the ability of recombinant vaccinia virus (VV) and bacterial plasmid, both carrying the NS1 gene from tick-borne encephalitis (TBE) virus under the control of different promoters, to protect mice against lethal challenge using a heterologous prime-boost vaccination protocol.     

SEGMENTATION APPROACHES THAT DIFFERENTIATE CONSUMPTION FREQUENCY FROM SENSORY PREFERENCE1

People can eat a food without having a strong preference for it, and people can prefer a food without eating it. Given this seeming disconnect between attitude and behavior, which type of measure or segment can best be used to profile or identify loyal consumer segments of a food, such as soy? This research compares a usage‐based method (heavy‐light‐nonusers) with a new attitude‐based method (seeker‐neutral‐avoider), and finds that the attitude‐based method differentiates purchase‐related intentions better than the usage‐based method. Implications for profiling consumer taste patterns and consumer segments are provided.     

Characterization and molecular genetic complementation of mutants affecting dimorphism in the fungus ustilago maydis

Ustilago maydis, the causal agent of corn smut disease, displays dimorphic growth in which it alternates between a unicellular, nonpathogenic yeast-like form and a dikaryotic, pathogenic filamentous form. Previously, a constitutively filamentous haploid mutant was obtained. Complementation of this mutant led to the isolation of the gene encoding adenylate cyclase, uac1. Secondary mutagenesis of a uac1 disruption strain allowed the isolation of a large number of suppressor mutants, termed ubc, for Ustilago bypass of cyclase, lacking the filamentous phenotype. Analysis of one of these suppressor mutants previously led to the identification of the ubc1 gene, encoding the regulatory subunit of cAMP-dependent protein kinase. In this report we describe the isolation of cosmids containing three new ubc genes, termed ubc2, ubc3, and ubc4. We also describe the morphology of the ubc2, ubc3, and ubc4 mutants in a uac1- background as well as in a background with a functional uac1 gene. In addition, we describe several mutant strains not complemented with any of the genes currently in hand and that are thus presumed to possess mutations in additional ubc genes. Copyright 1998 Academic Press.     

Body size effects and rates of cytochrome b evolution in tube-nosed seabirds

Variation in rates of molecular evolution now appears to be widespread. The demonstration that body size is correlated with rates of molecular evolution suggests that physiological and ecological factors may be involved in molecular rate variation, but large-scale comparative studies are still lacking. Here, we use complete cytochrome b sequences from 85 species of tube-nosed seabirds (order Procellariiformes) and 5 outgroup species of penguins (order Sphenisciformes) to test for an association between body mass and rates of molecular evolution within the former avian order. Cladistic analysis of the 90 sequences estimates a phylogeny largely consistent with the traditional taxonomy of the Procellariiformes. The Diomedeidae, Procellariidae, and Pelecanoididae are monophyletic, while the Hydrobatidae are basal and paraphyletic. However, the two subfamilies within the Hydrobatidae (Hydrobatinae and Oceanitinae) are monophyletic. A likelihood ratio test detects significant deviation from clocklike evolution in our data. Using a sign test for an association between body mass and branch length in the seabird phylogeny, we find that larger taxa tend to have shorter terminal branch lengths than smaller taxa. This observation suggests that rates of mitochondrial DNA evolution are slower for larger taxa. Rate calibrations based on the fossil record reveal concordant body size effects. We interpret these results as evidence for a metabolic rate effect, as the species in this order exhibit large differences in metabolic rates, which are known to be highly correlated with body mass in this group. Our results support previous findings of body size effects and show that this effect can be significant even within a single avian order. This suggests that even lineage-specific molecular clocks may not be tenable if calibrations involve taxa with different metabolic rates.      

Evidence that Benzo(a) pyrene-resistant, aryl hydrocarbon hydroxylase-deficient variants of mouse hepatoma line, Hepa-1, are mutational in origin

Treatment of Hepa-1 with N-methyl-N'-nitro-N-nitrosoguanidine, ethyl methanesulfonate, UV light, or ICR-191G, increased the frequency of benzo(a)pyrene-resistant (BPr) clones. The relative efficacies of the mutagens at increasing the frequency of BPr clones correlated with their efficacies a inducing 6-thioguanine-resistant clones. Evidence was obtained that the mutagens induced the BPr variants rather than selecting for BPr cells that preexisted in the treated cultures. All variants tested had reduced AHH activities and phenotypes that were stable over time in culture. Certain "leaky" variants with residual AHH activities and low cloning efficiencies in BP were further selected in BP and subclones isolated. Half the subclones were indistinguishable from their parents, while the majority of the remainder retained at least half of their parents' AHH activity. The marked stability of the phenotype of the variants, and their induction by mutagens, suggests that they are bona fide mutants.