Influence of intergenerational in utero parental energy and nutrient restriction on offspring growth in rural Gambia.

The prenatal environment can alter an individual's developmental trajectory with long-lasting effects on health. Animal models demonstrate that the impact of the early life environment extends to subsequent generations, but there is a paucity of data from human populations on intergenerational transmission of environmentally induced phenotypes. Here we investigated the association of parental exposure to energy and nutrient restriction in utero on their children's growth in rural Gambia. In a Gambian cohort with infants born between 1972 and 2011, we used multiple regression to test whether parental season of birth predicted offspring birth weight (n = 2097) or length (n = 1172), height-for-age z score (HAZ), weight-for-height z score (WHZ), and weight-for-age z score (WAZ) at 2 yr of age (n = 923). We found that maternal exposure to seasonal energy restriction in utero was associated with reduced offspring birth length (crude:-4.2 mm, P = 0.005; adjusted: -4.0 mm, P = 0.02). In contrast, paternal birth season predicted offspring HAZ at 24 mo (crude: -0.21, P = 0.005; adjusted: -0.22, P = 0.004) but had no discernible impact at birth. Our results indicate that periods of nutritional restriction in a parent's fetal life can have intergenerational consequences in human populations. Fetal growth appears to be under matriline influence, and postnatal growth appears to be under patriline intergenerational influences.-Eriksen, K. G., Radford, E. J., Silver, M. J., Fulford, A. J. C., Wegmüller, R., Prentice, A. M. Influence of intergenerational in utero parental energy and nutrient restriction on offspring growth in rural Gambia

Establishment of environmentally sensitive DNA methylation states in the very early human embryo.

The molecular mechanisms responsible for the developmental origins of later disease are currently unknown. We previously demonstrated that women's periconceptional nutrition predicts their offspring's DNA methylation at metastable epialleles (MEs). We present a genome-wide screen yielding 687 MEs and track their trajectories across nine developmental stages in human in vitro fertilization embryos. MEs exhibit highly unusual methylation dynamics across the implantation-gastrulation transition, producing a large excess of intermediate methylation states, suggesting the potential for differential programming in response to external signals. Using a natural experiment in rural Gambia, we show that genomic regions sensitive to season of conception are highly enriched for MEs and show similar atypical methylation patterns. MEs are enriched for proximal enhancers and transcription start sites and are influenced by genotype. Together, these observations position MEs as distinctive epigenomic features programmed in the early embryo, sensitive to genetic and periconceptional environment, and with the potential to influence phenotype

Periconceptional environment predicts leukocyte telomere length in a cross-sectional study of 7-9 year old rural Gambian children

Early life exposures are important predictors of adult disease risk. Although the underlying mechanisms are largely unknown, telomere maintenance may be involved. This study investigated the relationship between seasonal differences in parental exposures at time of conception and leukocyte telomere length (LTL) in their offspring. LTL was measured in two cohorts of children aged 2 yrs (N = 487) and 7–9 yrs (N = 218). The association between date of conception and LTL was examined using Fourier regression models, adjusted for age, sex, leukocyte cell composition, and other potential confounders. We observed an effect of season in the older children in all models [likelihood ratio test (LRT) χ²2 = 7.1, p = 0.03; fully adjusted model]. LTL was greatest in children conceived in September (in the rainy season), and smallest in those conceived in March (in the dry season), with an effect size (LTL peak–nadir) of 0.60 z-scores. No effect of season was evident in the younger children (LRT χ²2 = 0.87, p = 0.65). The different results obtained for the two cohorts may reflect a delayed effect of season of conception on postnatal telomere maintenance. Alternatively, they may be explained by unmeasured differences in early life exposures, or the increased telomere attrition rate during infancy

DNA methylation at a nutritionally sensitive region of the PAX8 gene is associated with thyroid volume and function in Gambian children.

Funder: Wellcome TrustPAX8 is a key thyroid transcription factor implicated in thyroid gland differentiation and function, and PAX8 gene methylation is reported to be sensitive to the periconceptional environment. Using a novel recall-by-epigenotype study in Gambian children, we found that PAX8 hypomethylation at age 2 years is associated with a 21% increase in thyroid volume and an increase in free thyroxine (T4) at 5 to 8 years, the latter equivalent to 8.4% of the normal range. Free T4 was associated with a decrease in DXA-derived body fat and bone mineral density. Furthermore, offspring PAX8 methylation was associated with periconceptional maternal nutrition, and methylation variability was influenced by genotype, suggesting that sensitivity to environmental exposures may be under partial genetic control. Together, our results demonstrate a possible link between early environment, PAX8 gene methylation and thyroid gland development and function, with potential implications for early embryonic programming of thyroid-related health and disease

Environmentally sensitive hotspots in the methylome of the early human embryo

In humans, DNA methylation marks inherited from gametes are largely erased following fertilisation, prior to construction of the embryonic methylome. Exploiting a natural experiment of seasonal variation including changes in diet and nutritional status in rural Gambia, we analysed three datasets covering two independent child cohorts and identified 259 CpGs showing consistent associations between season of conception (SoC) and DNA methylation. SoC effects were most apparent in early infancy, with evidence of attenuation by mid-childhood. SoC-associated CpGs were enriched for metastable epialleles, parent-of-origin-specific methylation and germline differentially methylated regions, supporting a periconceptional environmental influence. Many SoC-associated CpGs overlapped enhancers or sites of active transcription in H1 embryonic stem cells and fetal tissues. Half were influenced but not determined by measured genetic variants that were independent of SoC. Environmental 'hotspots' providing a record of environmental influence at periconception constitute a valuable resource for investigating epigenetic mechanisms linking early exposures to lifelong health and disease

Evidence for negative selection of gene variants that increase dependence on dietary choline in a Gambian cohort

Choline is an essential nutrient, and the amount needed in the diet is modulated by several factors. Given geographical differences in dietary choline intake and disparate frequencies of single-nucleotide polymorphisms (SNPs) in choline metabolism genes between ethnic groups, we tested the hypothesis that 3 SNPs that increase dependence on dietary choline would be under negative selection pressure in settings where choline intake is low: choline dehydrogenase (CHDH) rs12676, methylenetetrahydrofolate reductase 1 (MTHFD1) rs2236225, and phosphatidylethanolamine-N-methyltransferase (PEMT) rs12325817. Evidence of negative selection was assessed in 2 populations: one in The Gambia, West Africa, where there is historic evidence of a choline-poor diet, and the other in the United States, with a comparatively choline-rich diet. We used 2 independent methods, and confirmation of our hypothesis was sought via a comparison with SNP data from the Maasai, an East African population with a genetic background similar to that of Gambians but with a traditional diet that is higher in choline. Our results show that frequencies of SNPs known to increase dependence on dietary choline are significantly reduced in the low-choline setting of The Gambia. Our findings suggest that adequate intake levels of choline may have to be reevaluated in different ethnic groups and highlight a possible approach for identifying novel functional SNPs under the influence of dietary selective pressure

Progress on the development of the Stellar X-ray Polarimeter on board of the Spectrum-X-Gamma Satellite

We present the status of the Stellar X-ray Polarimeter at November’94 devoted to measure linear polarisation from cosmic X-ray sources between 2 keV and 15 keV which will be flown on the Spectrum-X-Gamma Satellite. In particular, we focus on the performances of the engineering model after the calibrations at Lawrence Livermore Laboratories and on the improvements which have been introduced on the four flight model imaging proportional counters which are key parts of the experiment

Report of the Regional Co-ordination Meeting for the North Sea and Eastern Arctic (RCM NS&EA) 2015

The RCM NS&EA met 31st August - 4th September 2015 at den Haag, Netherlands with 27 participants form 11 member states and autonomous regions attending, including representatives of ICES and the Commission. National correspondents from Spain, UK, Denmark, Lithuania, Germany, Sweden and the Netherlands were present. The meeting was co-chaired by Katja Ringdahl (Sweden) and Alastair Pout (Scotland). The RCM N&SEA considered the recommendations from the 11th Liasion meeting and summaries were presented of the work of expert groups and end users for the 2014-15 period to the plenary session of the meeting. The expert groups included WGCATCH, PGDATA, WKISCON2, WKRDB 2014-01, RDB–SC, STECF and the Zagreb meeting on transversal variables. ICES, as a main end user, provided feedback. A summary was presented of the progress in the regional coordination project (fishPi). This project involves over 40 participants from 12 members states from NS&EA, NA and Baltic regions, two external statistical experts, and ICES. The project has a wide scope of regional cooperation issues including sampling designs, data formats, code lists, PETS, stomach sampling, small scale and recreational sampling, and data quality software production. It has a budget of €400,000, and a one year time line and with a planned completion date of April 2016. A project with identical aims is running in paralleled in the Mediterranean and Black Sea regions The majority of the ToRs of the RCM NS&EA were addressed by three subgroups: one concerned with data analysis, one with the landing obligation, and one with issues particularly related to role and work of national correspondents

Designing Hybrid Gifts

Hybrid gifting combines physical artefacts and experiences with digital interactivity to generate new kinds of gifts. Our review details how gifting is a complex social phenomenon and how digital gifting is less engaging than physical gifting for both givers and receivers. Employing a Research Through Design approach, we developed a portfolio of four hybrid gifting experiences: an augmented advent calendar; edible music tracks; personalised museum tours; and a narrated city walk. Our reflection addresses three concepts: hybrid wrapping where physical gifts become wrapped in digital media and vice versa; the importance of effortful interactions that are visible and pleasurable; and the need to consider social obligation, including opportunities for acknowledgement and reciprocation, dealing with embarrassment, and recognising the distinction between giving and sharing. Our concepts provide guidance to practitioners who wish to design future gifting experiences while helping HCI researchers engage with the concept of gifting in a nuanced way

The High-Energy X-ray Probe (HEX-P): the circum-nuclear environment of growing supermassive black holes

Ever since the discovery of the first active galactic nuclei (AGN), substantial observational and theoretical effort has been invested into understanding how massive black holes have evolved across cosmic time. Circum-nuclear obscuration is now established as a crucial component, with almost every AGN observed known to display signatures of some level of obscuration in their X-ray spectra. However, despite more than six decades of effort, substantial open questions remain: how does the accretion power impact the structure of the circum-nuclear obscurer? What are the dynamical properties of the obscurer? Can dense circum-nuclear obscuration exist around intrinsically weak AGN? How many intermediate mass black holes occupy the centers of dwarf galaxies? In this paper, we showcase a number of next-generation prospects attainable with the High-Energy X-ray Probe (HEX-P1) to contribute toward solving these questions in the 2030s. The uniquely broad (0.2–80 keV) and strictly simultaneous X-ray passband of HEX-P makes it ideally suited for studying the temporal co-evolution between the central engine and circum-nuclear obscurer. Improved sensitivities and reduced background will enable the development of spectroscopic models complemented by current and future multi-wavelength observations. We show that the angular resolution of HEX-P both below and above 10 keV will enable the discovery and confirmation of accreting massive black holes at both low accretion power and low black hole masses even when concealed by thick obscuration. In combination with other next-generation observations of the dusty hearts of nearby galaxies, HEX-P will be pivotal in paving the way toward a complete picture of black hole growth and galaxy co-evolution