Prenatal Folate and Choline Levels and Brain and Cognitive Development in Children: A Critical Narrative Review

Women’s nutritional status during pregnancy can have long-term effects on children’s brains and cognitive development. Folate and choline are methyl-donor nutrients and are important for closure of the neural tube during fetal development. They have also been associated with brain and cognitive development in children. Animal studies have observed that prenatal folate and choline supplementation is associated with better cognitive outcomes in offspring and that these nutrients may have interactive effects on brain development. Although some human studies have reported associations between maternal folate and choline levels and child cognitive outcomes, results are not consistent, and no human studies have investigated the potential interactive effects of folate and choline. This lack of consistency could be due to differences in the methods used to assess folate and choline levels, the gestational trimester at which they were measured, and lack of consideration of potential confounding variables. This narrative review discusses and critically reviews current research examining the associations between maternal levels of folate and choline during pregnancy and brain and cognitive development in children. Directions for future research that will increase our understanding of the effects of these nutrients on children’s neurodevelopment are discussed.

A Quantified Study of the Resistance of Duplex Stainless Steels to HISC: Part 1 - Significance of the three-dimensional phase distributions and morphological properties on hydrogen transport

This paper is associated with a larger programme of research, studying the resistance to hydrogen-induced stress cracking (HISC) of a wrought and a hot isostatically-pressed (HIP) UNS S31803 duplex stainless steel (DSS), with respect to both the independent and interactive effects of the three key components of HISC: microstructure, stress/strain, and hydrogen. In the first part presented here, several material properties such as the three-dimensional (3D) microstructure, distribution and morphology/geometry of the two phases, i.e. ferrite and austenite, and their significance on hydrogen transport have been determined quantitatively, using X-ray computed tomography (CT) microstructural data analysis and modelling. This provided a foundation for the study to compare resistance to HISC initiation and propagation of the two DSSs with differing microstructures, using hydrogen permeation measurements, environmental fracture toughness testing of single-edge notched bend test specimens, in the Part 2 paper of this study [1].

Ability to Swim (Not Morphology or Environment) Explains Interspecific Differences in Crinoid Arm Regrowth

Regrowth of body parts occurs in almost every phylum of the animal kingdom, but variation in this process across environmental, morphological, and behavioral gradients remains poorly understood. We examined regeneration patterns in feather stars – a group known for a wide range of morphologies and behaviors and up to a forty-fold difference in arm regeneration rates – and found that the variation in arm regeneration rates is best explained by swimming ability, not temperature, food supply, morphology (total number of arms and number of regenerating arms), or degree of injury. However, there were significant interactive effects of morphology on rates of regeneration of the main effect (swimming ability). Notably, swimmers grew up to three-fold faster than non-swimmers. The temperate feather star Florometra serratissima regenerated faster under warmer scenarios, but its rates fell within that of the tropical species suggesting temperature can account for intraspecific but not interspecific differences. We urge comparative molecular investigations of crinoid regeneration to identify the mechanisms responsible for the observed interspecific differences, and potentially address gaps in stem cell research.

The interactive effects of pre-pregnancy body mass index, thyroid function, and blood lipid levels on the risk of gestational diabetes mellitus: a crossover analysis

Background Studies have demonstrated the associations between pre-pregnancy obesity, thyroid dysfunction, dyslipidemia, and increased risk of gestational diabetes mellitus (GDM) in pregnant women. This study was designed to investigate whether and to what extent, the interactions between these factors contribute to the risk of GDM. Methods A case-control study of 232 GDM cases and 696 controls was conducted among pregnant women from Hangzhou, China. Multiple logistic regression analysis was applied to identify independent risk factors of GDM. Crossover analysis was performed to assess the interactive effects of pre-pregnancy body mass index (pBMI), thyroid hormones, blood lipid profiles on the risk of GDM. The indexes including attributable proportion (AP) to the interaction and the relative excess risk due to interaction (RERI) were calculated. Results Chinese pregnant women with pBMI > 23 kg/m2 (adjusted: OR=4.162, P<0.001), high triglyceride levels (> 2.30 mmol/L) (adjusted: OR=1.735, P<0.001) and the free triiodothyronine/free thyroxine (FT3/FT4) ratio ≥0.502 (OR=4.162, P<0.001) have significantly increased risk of GDM. Crossover analysis indicated that there were significant interactions between pre-pregnancy overweight/obesity and FT3/FT4 ≥0.502(AP=0.550, P<0.001; RERI=7.586, P=0.009), high TG levels and FT3/FT4≥0.502 (AP=0.348, 95%CI=0.081~0.614, P=0.010; RERI =2.021, 95%CI=0.064~3.978, P=0.043) on the risk of GDM. Conclusion The interactions between pBMI and FT3/FT4 ratio, TG level, and FT3/FT4 ratio may have significant impacts on the risk of GDM in pregnant women. Such findings may help improve our understanding of the pathogenesis of GDM as well as develop comprehensive strategies for the management of GDM.

Characterization and Mapping of retr04, retr05 and retr06 Broad-Spectrum Resistances to Turnip Mosaic Virus in Brassica juncea, and the Development of Robust Methods for Utilizing Recalcitrant Genotyping Data

Turnip mosaic virus (TuMV) induces disease in susceptible hosts, notably impacting cultivation of important crop species of the Brassica genus. Few effective plant viral disease management strategies exist with the majority of current approaches aiming to mitigate the virus indirectly through control of aphid vector species. Multiple sources of genetic resistance to TuMV have been identified previously, although the majority are strain-specific and have not been exploited commercially. Here, two Brassica juncea lines (TWBJ14 and TWBJ20) with resistance against important TuMV isolates (UK 1, vVIR24, CDN 1, and GBR 6) representing the most prevalent pathotypes of TuMV (1, 3, 4, and 4, respectively) and known to overcome other sources of resistance, have been identified and characterized. Genetic inheritance of both resistances was determined to be based on a recessive two-gene model. Using both single nucleotide polymorphism (SNP) array and genotyping by sequencing (GBS) methods, quantitative trait loci (QTL) analyses were performed using first backcross (BC1) genetic mapping populations segregating for TuMV resistance. Pairs of statistically significant TuMV resistance-associated QTLs with additive interactive effects were identified on chromosomes A03 and A06 for both TWBJ14 and TWBJ20 material. Complementation testing between these B. juncea lines indicated that one resistance-linked locus was shared. Following established resistance gene nomenclature for recessive TuMV resistance genes, these new resistance-associated loci have been termed retr04 (chromosome A06, TWBJ14, and TWBJ20), retr05 (A03, TWBJ14), and retr06 (A03, TWBJ20). Genotyping by sequencing data investigated in parallel to robust SNP array data was highly suboptimal, with informative data not established for key BC1 parental samples. This necessitated careful consideration and the development of new methods for processing compromised data. Using reductive screening of potential markers according to allelic variation and the recombination observed across BC1 samples genotyped, compromised GBS data was rendered functional with near-equivalent QTL outputs to the SNP array data. The reductive screening strategy employed here offers an alternative to methods relying upon imputation or artificial correction of genotypic data and may prove effective for similar biparental QTL mapping studies.

DeepNull models non-linear covariate effects to improve phenotypic prediction and association power

Genome-wide association studies (GWASs) examine the association between genotype and phenotype while adjusting for a set of covariates. Although the covariates may have non-linear or interactive effects, due to the challenge of specifying the model, GWAS often neglect such terms. Here we introduce DeepNull, a method that identifies and adjusts for non-linear and interactive covariate effects using a deep neural network. In analyses of simulated and real data, we demonstrate that DeepNull maintains tight control of the type I error while increasing statistical power by up to 20% in the presence of non-linear and interactive effects. Moreover, in the absence of such effects, DeepNull incurs no loss of power. When applied to 10 phenotypes from the UK Biobank (n = 370K), DeepNull discovered more hits (+6%) and loci (+7%), on average, than conventional association analyses, many of which are biologically plausible or have previously been reported. Finally, DeepNull improves upon linear modeling for phenotypic prediction (+23% on average).

Interactive Effects of Maternal Vitamin D Status and Socio-Economic Status on the Risk of Spontaneous Abortion: Evidence from Henan Province, China

Background: Maternal vitamin D deficiency might generate adverse reproductive outcomes, and socio-economic inequalities in micronutrient-related diseases have often been found. This study aimed to explore the interactive effects of maternal vitamin D status and socio-economic status (SES) on risk of spontaneous abortion. Methods: A population-based case–control study was conducted including 293 women with spontaneous abortion and 498 control women in December 2009 and January, 2010 in Henan Province, China. Information on pregnancy outcomes, maternal demographic, lifestyle and exposure factors and blood samples were collected at the same time. Vitamin D deficiency was defined as 25(OH)D < 20 ng/mL. SES index was constructed with principal component analysis by aggregating women’s and their husbands’ education level and occupation, and household income and expenditure. Interactive effects were assessed on a multiplicative scale with ratio of the odds ratio (ROR). Results: Compared to those with high SES and vitamin D sufficiency, women with vitamin D deficiency and low SES index had an increased risk of spontaneous abortion (aOR: 1.99; 95% CI: 1.23–3.23). The ROR was 2.06 (95% CI: 1.04–4.10), indicating a significant positive multiplicative interaction. Conclusions: Maternal low SES may strengthen the effect of vitamin D deficiency exposure on spontaneous abortion risk in this Chinese population.