Maternal iron deficiency perturbs embryonic cardiovascular development in mice.

Congenital heart disease (CHD) is the most common class of human birth defects, with a prevalence of 0.9% of births. However, two-thirds of cases have an unknown cause, and many of these are thought to be caused by in utero exposure to environmental teratogens. Here we identify a potential teratogen causing CHD in mice: maternal iron deficiency (ID). We show that maternal ID in mice causes severe cardiovascular defects in the offspring. These defects likely arise from increased retinoic acid signalling in ID embryos. The defects can be prevented by iron administration in early pregnancy. It has also been proposed that teratogen exposure may potentiate the effects of genetic predisposition to CHD through gene-environment interaction. Here we show that maternal ID increases the severity of heart and craniofacial defects in a mouse model of Down syndrome. It will be important to understand if the effects of maternal ID seen here in mice may have clinical implications for women

Body image, body dissatisfaction and weight status in south asian children: a cross-sectional study

Background Childhood obesity is a continuing problem in the UK and South Asian children represent a group that are particularly vulnerable to its health consequences. The relationship between body dissatisfaction and obesity is well documented in older children and adults, but is less clear in young children, particularly South Asians. A better understanding of this relationship in young South Asian children will inform the design and delivery of obesity intervention programmes. The aim of this study is to describe body image size perception and dissatisfaction, and their relationship to weight status in primary school aged UK South Asian children. Methods Objective measures of height and weight were undertaken on 574 predominantly South Asian children aged 5-7 (296 boys and 278 girls). BMI z-scores, and weight status (underweight, healthy weight, overweight or obese) were calculated based on the UK 1990 BMI reference charts. Figure rating scales were used to assess perceived body image size (asking children to identify their perceived body size) and dissatisfaction (difference between perceived current and ideal body size). The relationship between these and weight status were examined using multivariate analyses. Results Perceived body image size was positively associated with weight status (partial regression coefficient for overweight/obese vs. non-overweight/obese was 0.63 (95% CI 0.26-0.99) and for BMI z-score was 0.21 (95% CI 0.10-0.31), adjusted for sex, age and ethnicity). Body dissatisfaction was also associated with weight status, with overweight and obese children more likely to select thinner ideal body size than healthy weight children (adjusted partial regression coefficient for overweight/obese vs. non-overweight/obese was 1.47 (95% CI 0.99-1.96) and for BMI z-score was 0.54 (95% CI 0.40-0.67)). Conclusions Awareness of body image size and increasing body dissatisfaction with higher weight status is established at a young age in this population. This needs to be considered when designing interventions to reduce obesity in young children, in terms of both benefits and harms

Automatic Robust Neurite Detection and Morphological Analysis of Neuronal Cell Cultures in High-content Screening

Cell-based high content screening (HCS) is becoming an important and increasingly favored approach in therapeutic drug discovery and functional genomics. In HCS, changes in cellular morphology and biomarker distributions provide an information-rich profile of cellular responses to experimental treatments such as small molecules or gene knockdown probes. One obstacle that currently exists with such cell-based assays is the availability of image processing algorithms that are capable of reliably and automatically analyzing large HCS image sets. HCS images of primary neuronal cell cultures are particularly challenging to analyze due to complex cellular morphology. Here we present a robust method for quantifying and statistically analyzing the morphology of neuronal cells in HCS images. The major advantages of our method over existing software lie in its capability to correct non-uniform illumination using the contrast-limited adaptive histogram equalization method; segment neuromeres using Gabor-wavelet texture analysis; and detect faint neurites by a novel phase-based neurite extraction algorithm that is invariant to changes in illumination and contrast and can accurately localize neurites. Our method was successfully applied to analyze a large HCS image set generated in a morphology screen for polyglutaminemediated neuronal toxicity using primary neuronal cell cultures derived from embryos of a Drosophila Huntington’s Disease (HD) model.National Institutes of Health (U.S.) (Grant

Genome-Wide Association Analysis of Oxidative Stress Resistance in Drosophila melanogaster

Background: Aerobic organisms are susceptible to damage by reactive oxygen species. Oxidative stress resistance is a quantitative trait with population variation attributable to the interplay between genetic and environmental factors. Drosophila melanogaster provides an ideal system to study the genetics of variation for resistance to oxidative stress. Methods and Findings: We used 167 wild-derived inbred lines of the Drosophila Genetic Reference Panel for a genomewide association study of acute oxidative stress resistance to two oxidizing agents, paraquat and menadione sodium bisulfite. We found significant genetic variation for both stressors. Single nucleotide polymorphisms (SNPs) associated with variation in oxidative stress resistance were often sex-specific and agent-dependent, with a small subset common for both sexes or treatments. Associated SNPs had moderately large effects, with an inverse relationship between effect size and allele frequency. Linear models with up to 12 SNPs explained 67–79 % and 56–66 % of the phenotypic variance for resistance to paraquat and menadione sodium bisulfite, respectively. Many genes implicated were novel with no known role in oxidative stress resistance. Bioinformatics analyses revealed a cellular network comprising DNA metabolism and neuronal development, consistent with targets of oxidative stress-inducing agents. We confirmed associations of seven candidate genes associated with natural variation in oxidative stress resistance through mutational analysis. Conclusions: We identified novel candidate genes associated with variation in resistance to oxidative stress that hav

Persistent Place-Making in Prehistory: the Creation, Maintenance, and Transformation of an Epipalaeolithic Landscape

Most archaeological projects today integrate, at least to some degree, how past people engaged with their surroundings, including both how they strategized resource use, organized technological production, or scheduled movements within a physical environment, as well as how they constructed cosmologies around or created symbolic connections to places in the landscape. However, there are a multitude of ways in which archaeologists approach the creation, maintenance, and transformation of human-landscape interrelationships. This paper explores some of these approaches for reconstructing the Epipalaeolithic (ca. 23,000–11,500 years BP) landscape of Southwest Asia, using macro- and microscale geoarchaeological approaches to examine how everyday practices leave traces of human-landscape interactions in northern and eastern Jordan. The case studies presented here demonstrate that these Epipalaeolithic groups engaged in complex and far-reaching social landscapes. Examination of the Early and Middle Epipalaeolithic (EP) highlights that the notion of “Neolithization” is somewhat misleading as many of the features we use to define this transition were already well-established patterns of behavior by the Neolithic. Instead, these features and practices were enacted within a hunter-gatherer world and worldview