Excess mortality rate during adulthood among Danish adoptees

Background and objective

Adoption studies have been used to disentangle the influence of genes from shared familial environment on various traits and disease risks. However, both the factors leading to adoption and living as an adoptee may bias the studies with regard to the relative influence of genes and environment compared to the general population. The aim was to investigate whether the cohort of domestic adoptees used for these studies in Denmark is similar to the general population with respect to all-cause mortality and cause-specific mortality rates.

Methods

13,111 adoptees born in Denmark in 1917, or later, and adopted in 1924 to 1947 were compared to all Danes from the same birth cohorts using standardized mortality ratios (SMR). The 12,729 adoptees alive in 1970 were similarly compared to all Danes using SMR as well as cause-specific SMR.

Results

The excess in all-cause mortality before age 65 years in adoptees was estimated to be 1.30 (95% CI 1.26–1.35). Significant excess mortality before age 65 years was also observed for infections, vascular deaths, cancer, alcohol-related deaths and suicide. Analyses including deaths after age 65 generally showed slightly less excess in mortality, but the excess was significant for all-cause mortality, cancer, alcohol-related deaths and suicides.

Conclusion

Adoptees have an increased all-cause mortality compared to the general population. All major specific causes of death contributed, and the highest excess is seen for alcohol-related deaths.     

Food resources, chemical signaling, and nest mate recognition in the ant Formica aquilonia

Animals such as social insects that live in colonies can recognizeintruders from other colonies of the same or different speciesusing colony-specific odors. Such colony odors usually haveboth a genetic and an environmental origin. When within-colonyrelatedness is high (i.e., one or very few reproductive queens),colonies comprise genetically distinct entities, and recognitionbased on genetic cues is reliable. However, when nests containmultiple queens and colonies comprise multiple nests (polydomy),the use of purely genetically determined recognition labelsmay become impractical. This is due to high within-colony geneticheterogeneity and low between-colony genetic heterogeneity.This may favor the use of environmentally determined recognitionlabels. However, because nests within polydomous colonies maydiffer in their microenvironment, the use of environmental labelsmay also be impractical unless they are actively mixed amongthe nests. Using a laboratory experiment, we found that bothisolation per se and diet composition influenced the cuticularchemical profiles in workers of Formica aquilonia. In addition,the level of aggression increased when both the proportionsof dietary ingredients and the availability of food were altered.This suggests that increased aggression was mediated by changesin the chemical profile and that environmental cues can mediaterecognition between colonies. These results also suggest thatthe underlying recognition cues are mutable in response to extrinsicfactors such as the amount and the composition of food.     

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.     

Chemotaxonomic relevance of cardenolides in Urginea fugax

In a chemotaxonomic approach the investigation of a methanolic extract of bulbs of Urginea fugax (MORIS) STEINH. resulted in the detection of several cardenolides. The structure of a novel compound, named fugaxin (1), was established as 12alpha,14beta-dihydroxy-2alpha,3beta-(tetrahydro-3',5'-dihydroxy-4'-methoxy-6'-methyl-2H-pyran-2',4'-diylbisoxy)-card-4,20-dienolide by extensive NMR spectroscopic studies including 2D-NMR techniques (COSY, HSQC, HMQC) and selective 1D experiments (NOE, TOCSY) as well as HR-ESI-MS. The chemotaxonomic relevance of the occurrence of cardenolides in the genus Urginea is discussed.     

Habitat age, breeding system and kinship in the ant Formica fusca

In polygyne ants (multiple queens per colony) factors that affect the distribution and survival of queens may play a key role in shaping the population-wide mating system and colony kin structure. The aim of this paper was to study the breeding system in two populations of different age in the facultatively polygyne ant Formica fusca. Both the observed numbers of queens, and the relatedness patterns among queens, workers and colony fathers were compared in two adjacent populations (ages 17 years and > 100 years) in Southern Finland. The results showed that both the mating system and colony kin structure differed between the study populations. In the old population the relatedness among workers, queens and colony fathers was high. The queens were also related to their mates, resulting in significant inbreeding in workers, but not in queens. Finally, the number of queens per colony fluctuated between years, suggesting queen turnover, and nest-mate queens shared their reproduction unequally (reproductive skew). In the younger population relatedness among queens and workers was lower than in the old population, and the colony fathers were unrelated. Furthermore, inbreeding was absent, and no conclusive evidence was found for reproductive skew among nest-mate queens. Finally, the number of queens per colony appeared more stable between years, although queen turnover occurred also in this population. The observed differences in dispersal and mating behaviour are discussed in the light of a potential connection between population age and habitat saturation.     

Faecal corticosterone and immunoglobulin A in young adult rats

Quantitative analyses of relevant molecules in faeces may have potential as future non-invasive measures of stress. This study examined levels of faecal corticosterone and immunoglubulin A (IgA) in young adult rats and how these levels varied according to age, gender and time of day. Faecal samples were collected from 40 young adult rats (7 weeks old, n = 20 and 10 weeks old, n = 20) of both sexes from two time windows: day and night. The concentrations of corticosterone and IgA were measured by ELISAs following organic solvent extraction and aqueous extraction, respectively, of the molecules from faecal pellets. The production of faeces per time unit was higher in males than in females, and linear correlations were found between the faecal concentrations of corticosterone and IgA and total amounts of the respective molecules excreted in faeces per kg body weight per hour. In all further analyses the levels of the two molecules were calculated as amounts secreted per kg of body weight per hour. There was no gender difference between females and males in the production of corticosterone and IgA, but 7-week-old animals excreted significantly higher amounts of both molecules than did 10-week-old rats. The levels of IgA excreted by female rats were higher in the evening than in the morning, and male rats excreted higher concentrations of corticosterone in the morning than in the evening.     

Flavonoids from Achillea nobilis L

The detailed investigation of a methanolic extract of aerial parts of Achillea nobilis resulted in the isolation of 10 flavonoids. A new C-glycosylflavone, luteolin-6-C-apiofuranosyl-(1'-->2')-glucoside, was isolated besides orientin, isoorientin, vitexin, isoschaftoside, luteolin-7-O-beta-glucuronide, luteolin-4'-O-beta-glucoside and quercetin-3-O-methyl ether and two rare flavonolglycosides, quercetin-3-O-alpha-arabinosyl-(1'-->6')-glucoside and quercetin-3-O-methylether-7-O-beta-glucoside. The structures were established either by comparison with authentic substances or by UV, 1H NMR and 13C NMR spectroscopic methods including 2D-NMR techniques and ESI-MS.     

Hypotonicity-induced increases in duodenal mucosal permeability facilitates adjustment of luminal osmolality

The integrated response to hypotonic NaCl solutions (100, 50, 25, and 0 mM NaCl) in proximal duodenum of anesthetized rats was examined. Luminal alkalinization, fluid flux, duodenal contractions, blood-to-lumen clearance of 51Cr-labeled EDTA (mucosal permeability), and perfusate osmolality were studied in the absence and presence of the cyclooxygenase inhibitor indomethacin. In response to hypotonic solutions net fluid absorption, increases in permeability and perfusate osmolality were markedly higher in indomethacin-treated animals than in controls, and these effects were diminished by the nicotinic-receptor antagonist hexamethonium. Infusion of iloprost, a stable PGI2 analog, to indomethacin-treated animals markedly reduced the hypotonicity-induced increase in mucosal permeability and diminished the rise in perfusate osmolality. Lowering the NaCl concentration in the perfusion solution but maintaining isotonicity with mannitol had no effect on mucosal permeability. Very good linear correlations were obtained between the degree of luminal hypotonicity and the increase in permeability and between increases in permeability and perfusate osmolality. It is concluded that luminal hypotonicity increases duodenal mucosal permeability. The hypotonicity-induced increase in permeability modulated by prostaglandins and nicotinic receptors fulfills the function of increasing blood-to-lumen transport of Na+ facilitating adjustment of luminal osmolality.