Children's biobehavioral reactivity to challenge predicts DNA methylation in adolescence and emerging adulthood.

A growing body of research has documented associations between adverse childhood environments and DNA methylation, highlighting epigenetic processes as potential mechanisms through which early external contexts influence health across the life course. The present study tested a complementary hypothesis: indicators of children's early internal, biological, and behavioral responses to stressful challenges may also be linked to stable patterns of DNA methylation later in life. Children's autonomic nervous system reactivity, temperament, and mental health symptoms were prospectively assessed from infancy through early childhood, and principal components analysis (PCA) was applied to derive composites of biological and behavioral reactivity. Buccal epithelial cells were collected from participants at 15 and 18 years of age. Findings revealed an association between early life biobehavioral inhibition/disinhibition and DNA methylation across many genes. Notably, reactive, inhibited children were found to have decreased DNA methylation of the DLX5 and IGF2 genes at both time points, as compared to non-reactive, disinhibited children. Results of the present study are provisional but suggest that the gene's profile of DNA methylation may constitute a biomarker of normative or potentially pathological differences in reactivity. Overall, findings provide a foundation for future research to explore relations among epigenetic processes and differences in both individual-level biobehavioral risk and qualities of the early, external childhood environment

Strategies to calculate water binding free energies in protein–ligand complexes

Water molecules are commonplace in protein binding pockets, where they can typically form a complex between the protein and a ligand or become displaced upon ligand binding. As a result, it is often of great interest to establish both the binding free energy and location of such molecules. Several approaches to predicting the location and affinity of water molecules to proteins have been proposed and utilized in the literature, although it is often unclear which method should be used under what circumstances. We report here a comparison between three such methodologies, Just Add Water Molecules (JAWS), Grand Canonical Monte Carlo (GCMC), and double-decoupling, in the hope of understanding the advantages and limitations of each method when applied to enclosed binding sites. As a result, we have adapted the JAWS scoring procedure, allowing the binding free energies of strongly bound water molecules to be calculated to a high degree of accuracy, requiring significantly less computational effort than more rigorous approaches. The combination of JAWS and GCMC offers a route to a rapid scheme capable of both locating and scoring water molecules for rational drug design

Scales of governance: Translating multiscalar transitional pathways in South Africa's energy landscape

In this paper, we argue for a multiscalar focus on the governance of energy policy and practice. This perspective reveals the translation of agendas and policies across scales stretching from the global to the local. We analyse South Africa’s energy landscape, which is influenced by: a highly complex and dynamic set of generation and production networks, policy strategies, multiple state and non-state actors, and the continuing impact of apartheid. In the paper, we establish a dialogue between Actor-Network Theory and studies of socio-technical transitions to analyse the translation and purification of discourses and practices across scales, and to consider how these processes may impact on spatialised processes of energy transition

Birthweight, HIV exposure and infant feeding as predictors of malnutrition in Botswanan infants

Background: A better understanding of the nutritional status of infants who are HIV-Exposed-Uninfected (HEU) and HIV-Unexposed-Uninfected (HUU) during their first 1000 days is key to improving population health, particularly in sub-Saharan Africa. Methods: A cross-sectional study compared the nutritional status, feeding practices and determinants of nutritional status of HEU and HUU infants residing in representative selected districts in Botswana during their first 1000 days of life. Four hundred and thirteen infants (37.3% HIV-exposed), aged 6–24 months, attending routine child health clinics, were recruited. Anthropometric, 24-h dietary intake and socio-demographic data was collected. Anthropometric Z-scores were calculated using 2006 World Health Organization growth standards. Modelling of the determinants of malnutrition was undertaken using logistic regression. Results: Overall, the prevalences of stunting, wasting and being underweight were 10.4%, 11.9% and 10.2%, respectively. HEU infants were more likely to be underweight (15.6% versus 6.9%), (P &lt; 0.01) and stunted (15.6% versus 7.3%), (P &lt; 0.05) but not wasted (P = 0.14) than HUU infants. HEU infants tended to be formula fed (82.5%), whereas HUU infants tended to breastfeed (94%) for the first 6 months (P &lt; 0.001). Significant predictors of nutritional status were HIV exposure, birthweight, birth length, APGAR (appearance, pulse, grimace, activity and respiration) score and mother/caregiver's education with little influence of socio-economic status. Conclusions: HEU infants aged 6–24 months had worse nutritional status compared to HUU infants. Low birthweight was the main predictor of undernutrition in this population. Optimisation of infant nutritional status should focus on improving birthweight. In addition, specific interventions should target HEU infants aiming to eliminate growth disparity between HEU and HUU infants.</p

The biological embedding of early-life socioeconomic status and family adversity in children's genome-wide DNA methylation.

AimTo examine variation in child DNA methylation to assess its potential as a pathway for effects of childhood social adversity on health across the life course.Materials &amp; methodsIn a diverse, prospective community sample of 178 kindergarten children, associations between three types of social experience and DNA methylation within buccal epithelial cells later in childhood were examined.ResultsFamily income, parental education and family psychosocial adversity each associated with increased or decreased DNA methylation (488, 354 and 102 sites, respectively) within a unique set of genomic CpG sites. Gene ontology analyses pointed to genes serving immune and developmental regulation functions.ConclusionFindings provided support for DNA methylation as a biomarker linking early-life social experiences with later life health in humans

Zoonoses under our noses.

This is the final version of the article. Available from Elsevier via the DOI in this record.One Health is an effective approach for the management of zoonotic disease in humans, animals and environments. Examples of the management of bacterial zoonoses in Europe and across the globe demonstrate that One Health approaches of international surveillance, information-sharing and appropriate intervention methods are required to successfully prevent and control disease outbreaks in both endemic and non-endemic regions. Additionally, a One Health approach enables effective preparation and response to bioterrorism threats.A.R.C. is supported by a BBSRC iCASE Studentship in partnership with the University of Exeter and the Defence Science and Technology Laboratory (Dstl) (Grand no.BB/M016404/1). S.R. is supported by the BBSRC grant number BB/N001591/1