Effect of the early-life nutritional environment on fecundity and fertility of mammals.

The early-life developmental environment is instrumental in shaping our overall adult health and well-being. Early-life diet and endocrine exposure may independently, or in concert with our genetic constitution, induce a pathophysiological process that amplifies with age and leads to premature morbidity and mortality. Recently, this has become known as 'programming' but is akin to 'maternal effects' described for many years in the biological sciences and is defined as any influence that acts during critical developmental windows to induce long-term changes in the organisms' phenotype. To date, such delayed maternal effects have largely been characterized in terms of susceptibility to cardiovascular or metabolic disease. Here, we review evidence from experimental animal species, non-human primates and man for an effect of the early-life nutritional environment on adult fecundity and fertility. In addition, using a database of pedigree sheep, we also specifically test the hypothesis that being born small for gestational age with or without post-natal growth acceleration directly programmes fertility. We conclude that there is a lack of compelling evidence to suggest pre-natal undernutrition may directly reduce adult fecundity and fertility, but may exert some effects secondarily via an increased incidence of 'metabolic syndrome'. Possible effects of being born relatively large on subsequent fecundity and fertility warrant further investigation

Compressive behaviour of double skin sections with stainless steel outer tubes and recycled aggregate concrete

An experimental and numerical study into the behaviour of concrete-filled double skin tubular (CFDST) stub columns is presented. A total of eight axial compression tests were carried out, four utilising conventional concrete and four with recycled aggregate concrete. The stub columns were circular in cross-section and each comprised an austenitic stainless steel outer tube and a carbon steel inner tube, of varying dimensions. Accordingly, hollow ratios of 0.67 and 0.55 were considered. The recycled coarse aggregate was made by crushing test specimens from a previous research project, and a replacement ratio of 50% was adopted. During the experiments, similar structural behaviour and failure modes were observed between the specimens with conventional and recycled aggregate concrete. To investigate the behaviour further, a finite element model was developed in ABAQUS; validation of the model against the experimental results from the current work as well as data available in the literature is described. The finite element model was employed to conduct a parametric study to examine the load-bearing contributions of the constituent components of CFDST sections and to assess the influence of the hollow ratio on the structural behaviour. The experimental and numerical ultimate loads are compared with the capacity predictions determined using available design procedures. Overall, the results show that CFDST stub columns with recycled aggregate concrete can achieve similar capacities to their conventional concrete counterparts, demonstrating the potential for the wider use of recycled aggregate concrete, towards more sustainable structural solutions

Energy status and HIF signalling in chorionic villi show no evidence of hypoxic stress during human early placental development.

Early human placental and embryonic development occurs in a physiologically low oxygen environment supported by histiotrophic secretions from endometrial glands. In this study, we compare the placental metabolomic profile in the first, second and third trimesters to determine whether the energy demands are adequately met in the first trimester. We investigated whether hypoxia-inducible factors, HIF-1α and/or HIF-2α, might regulate transcription during the first trimester. First and second trimester tissue was collected using a chorionic villus sampling-like (CVS) technique. Part of each villus sample was frozen immediately and the remainder cultured under 2 or 21% O2 ± 1 mM H2O2, and ±the p38 MAPK pathway inhibitor, PD169316. Levels of HIF-1α were assessed by western blotting and VEGFA, PlGF and GLUT3 transcripts were quantified by RT-PCR. Term samples were collected from normal elective Caesarean deliveries. There were no significant differences in concentrations of ADP, NAD(+), lactate, and glucose, and in the ATP/ADP ratio, across gestational age. Neither HIF-1α nor HIF-2α could be detected in time-zero CVS samples. However, culture under any condition (2 or 21% O2 ± 1 mM H2O2) increased HIF-1α and HIF-2α. HIF-1α and HIF-2α were additionally detected in specimens retrieved after curettage. HIF-1α stabilization was accompanied by significant increases in VEGFA and GLUT3 and a decrease in PlGF mRNAs. These effects were suppressed by PD169316. In conclusion, our data suggest that first trimester placental tissues are not energetically compromised, and that HIF-1α is unlikely to play an appreciable role in regulating transcriptional activity under steady-state conditions in vivo. However, the pathway may be activated by stress conditions.This work was supported by the Wellcome Trust (084804/2/08/Z). Funding to pay the Open Access publication charges for this article was provided by theWellcome Trust.This is the final published version. It originally appeared in Molecular Human Reproduction, at http://dx.doi.org/10.1093/molehr/gau105

Altruism can proliferate through group/kin selection despite high random gene flow

The ways in which natural selection can allow the proliferation of cooperative behavior have long been seen as a central problem in evolutionary biology. Most of the literature has focused on interactions between pairs of individuals and on linear public goods games. This emphasis led to the conclusion that even modest levels of migration would pose a serious problem to the spread of altruism in group structured populations. Here we challenge this conclusion, by analyzing evolution in a framework which allows for complex group interactions and random migration among groups. We conclude that contingent forms of strong altruism can spread when rare under realistic group sizes and levels of migration. Our analysis combines group-centric and gene-centric perspectives, allows for arbitrary strength of selection, and leads to extensions of Hamilton's rule for the spread of altruistic alleles, applicable under broad conditions.Comment: 5 pages, 2 figures. Supplementary material with 50 pages and 26 figure

Changes in ponderal index and body mass index across childhood and their associations with fat mass and cardiovascular risk factors at age 15

Background: Little is known about whether associations between childhood adiposity and later adverse cardiovascular health outcomes are driven by tracking of overweight from childhood to adulthood and/or by vascular and metabolic changes from childhood overweight that persist into adulthood. Our objective is to characterise associations between trajectories of adiposity across childhood and a wide range of cardiovascular risk factors measured in adolescence, and explore the extent to which these are mediated by fat mass at age 15. Methods and Findings: Using data from the Avon Longitudinal Study of Parents and Children, we estimated individual trajectories of ponderal index (PI) from 0-2 years and BMI from 2-10 years using random-effects linear spline models (N = 4601). We explored associations between PI/BMI trajectories and DXA-determined total-body fat-mass and cardiovascular risk factors at 15 years (systolic and diastolic blood pressure, fasting LDL-and HDL-cholesterol, triglycerides, C-reactive protein, glucose, insulin) with and without adjustment for confounders. Changes in PI/BMI during all periods of infancy and childhood were associated with greater DXA-determined fat-mass at age 15. BMI changes in childhood, but not PI changes from 0-2 years, were associated with most cardiovascular risk factors in adolescence; associations tended to be strongest for BMI changes in later childhood (ages 8.5-10), and were largely mediated by fat mass at age 15. Conclusion: Changes in PI/BMI from 0-10 years were associated with greater fat-mass at age 15. Greater increases in BMI from age 8.5-10 years are most strongly associated with cardiovascular risk factors at age 15, with much of these associations mediated by fat-mass at this age. We found little evidence supporting previous reports that rapid PI changes in infancy are associated with future cardiovascular risk. This study suggests that associations between early overweight and subsequent adverse cardiovascular health are largely due to overweight children tending to remain overweight

Computerized ICU Data Management Pitfalls and Promises

journal articleBiomedical Informatic

Bio-Benchmarking of Electronic Nose Sensors

BACKGROUND:Electronic noses, E-Noses, are instruments designed to reproduce the performance of animal noses or antennae but generally they cannot match the discriminating power of the biological original and have, therefore, been of limited utility. The manner in which odorant space is sampled is a critical factor in the performance of all noses but so far it has been described in detail only for the fly antenna. METHODOLOGY:Here we describe how a set of metal oxide (MOx) E-Nose sensors, which is the most commonly used type, samples odorant space and compare it with what is known about fly odorant receptors (ORs). PRINCIPAL FINDINGS:Compared with a fly's odorant receptors, MOx sensors from an electronic nose are on average more narrowly tuned but much more highly correlated with each other. A set of insect ORs can therefore sample broader regions of odorant space independently and redundantly than an equivalent number of MOx sensors. The comparison also highlights some important questions about the molecular nature of fly ORs. CONCLUSIONS:The comparative approach generates practical learnings that may be taken up by solid-state physicists or engineers in designing new solid-state electronic nose sensors. It also potentially deepens our understanding of the performance of the biological system

Multi-level selection and the issue of environmental homogeneity

In this paper, I identify two general positions with respect to the relationship between environment and natural selection. These positions consist in claiming that selective claims need and, respectively, need not be relativized to homogenous environments. I then show that adopting one or the other position makes a difference with respect to the way in which the effects of selection are to be measured in certain cases in which the focal population is distributed over heterogeneous environments. Moreover, I show that these two positions lead to two different interpretations – the Pricean and contextualist ones – of a type of selection scenarios in which multiple groups varying in properties affect the change in the metapopulation mean of individual-level traits. Showing that these two interpretations stem from different attitudes towards environmental homogeneity allows me to argue: a) that, unlike the Pricean interpretation, the contextualist interpretation can only claim that drift or selection is responsible for the change in frequency of the focal trait in a given metapopulation if details about whether or not group formation is random are specified; b) that the traditional main objection against the Pricean interpretation – consisting in arguing that the latter takes certain side-effects of individual selection to be effects of group selection – is unconvincing. This leads me to suggest that the ongoing debate about which of the two interpretations is preferable should concentrate on different issues than previously thought