No abstract

RationaleThe biochemical mechanisms underlying lung function are incompletely understood.ObjectivesTo identify and validate the plasma metabolome of lung function using two independent adult cohorts: discovery—the European Prospective Investigation into Cancer–Norfolk (EPIC-Norfolk, n=10 460) and validation—the VA Normative Aging Study (NAS) metabolomic cohort (n=437).MethodsWe ran linear regression models for 693 metabolites to identify associations with forced expiratory volume in one second (FEV1) and the ratio of FEV1 to forced vital capacity (FEV1/FVC), in EPIC-Norfolk then validated significant findings in NAS. Significance in EPIC-Norfolk was denoted using an effective number of tests threshold of 95%; a metabolite was considered validated in NAS if the direction of effect was consistent and p<0.05.Measurements and main resultsOf 156 metabolites that associated with FEV1 in EPIC-Norfolk after adjustment for age, sex, body mass index, height, smoking and asthma status, 34 (21.8%) validated in NAS, including several metabolites involved in oxidative stress. When restricting the discovery sample to men only, a similar percentage, 18 of 79 significant metabolites (22.8%) were validated. A smaller number of metabolites were validated for FEV1/FVC, 6 of 65 (9.2%) when including all EPIC-Norfolk as the discovery population, and 2 of 34 (5.9%) when restricting to men. These metabolites were characterised by involvement in respiratory track secretants. Interestingly, no metabolites were validated for both FEV1 and FEV1/FVC.ConclusionsThe validation of metabolites associated with respiratory function can help to better understand mechanisms of lung health and may assist the development of biomarkers.

Termites live in environments heavily colonized by diverse microorganisms, including pathogens. Eggs laid within the nest are likely to experience similar pathogenic pressures as those experienced by older nest-mates. Consequently, eggs may be under selective pressures to be immune-competent. Through in vitro experiments using developing embryos of the dampwood termite, Zootermopsis angusticollis , we tested the ontogeny, location and strength of their antifungal activity against the fungus, Metarhizium brunneum . Exterior washes of the chorion (extra-chorionic) and components within the chorion (intra-chorionic) were incubated with fungal conidia, which were then scored for viability. The fungistatic activity was location and developmental stage dependent. Extra-chorionic washes had relatively weak antifungal activity. Intra-chorionic homogenates were highly antifungal, exhibiting increased potency through development. The positive correlation between intra-chorionic fungistasis and developmental stage is probably due to the expression of endogenous proteins during embryogenesis. Boiling of both the extra-chorionic washes and the intra-chorionic contents rescued conidia viability, indicating the antifungal agent(s) is (are) heat-sensitive and probably proteinaceous. This study is the first to address embryonic antifungal activity in a hemimetabolous, eusocial taxon. Our results support the hypothesis that microbes have been significant agents of selection in termites, fostering the evolution of antifungal properties even in the most immature stage of development.