Maternal caffeine consumption during pregnancy and offspring cord blood DNA methylation:an epigenome-wide association study meta-analysis

Background: Prenatal caffeine exposure may influence offspring health via DNA methylation, but no large studies have tested this. Materials &amp; methods: Epigenome-wide association studies and differentially methylated regions in cord blood (450k or EPIC Illumina arrays) were meta-analyzed across six European cohorts (n = 3725). Differential methylation related to self-reported caffeine intake (mg/day) from coffee, tea and cola was compared with assess whether caffeine is driving effects. Results: One CpG site (cg19370043, PRRX1) was associated with caffeine and another (cg14591243, STAG1) with cola intake. A total of 12-22 differentially methylated regions were detected with limited overlap across caffeinated beverages. Conclusion: We found little evidence to support an intrauterine effect of caffeine on offspring DNA methylation. Statistical power limitations may have impacted our findings. </p

Different subcellular localisations of TRIM22 suggest species-specific function

The B30.2/SPRY domain is present in many proteins, including various members of the tripartite motif (TRIM) protein family such as TRIM5α, which mediates innate intracellular resistance to retroviruses in several primate species. This resistance is dependent on the integrity of the B30.2 domain that evolves rapidly in primates and exhibits species-specific anti-viral activity. TRIM22 is another positively selected TRIM gene. Particularly, the B30.2 domain shows rapid evolution in the primate lineage and recently published data indicate an anti-viral function of TRIM22. We show here that human and rhesus TRIM22 localise to different subcellular compartments and that this difference can be assigned to the positively selected B30.2 domain. Moreover, we could demonstrate that amino acid changes in two variable loops (VL1 and VL3) are responsible for the different subcellular localisations

Multiple Promoters and Alternative Splicing: Hoxa5 Transcriptional Complexity in the Mouse Embryo

The genomic organization of Hox clusters is fundamental for the precise spatio-temporal regulation and the function of each Hox gene, and hence for correct embryo patterning. Multiple overlapping transcriptional units exist at the Hoxa5 locus reflecting the complexity of Hox clustering: a major form of 1.8 kb corresponding to the two characterized exons of the gene and polyadenylated RNA species of 5.0, 9.5 and 11.0 kb. This transcriptional intricacy raises the question of the involvement of the larger transcripts in Hox function and regulation.We have undertaken the molecular characterization of the Hoxa5 larger transcripts. They initiate from two highly conserved distal promoters, one corresponding to the putative Hoxa6 promoter, and a second located nearby Hoxa7. Alternative splicing is also involved in the generation of the different transcripts. No functional polyadenylation sequence was found at the Hoxa6 locus and all larger transcripts use the polyadenylation site of the Hoxa5 gene. Some larger transcripts are potential Hoxa6/Hoxa5 bicistronic units. However, even though all transcripts could produce the genuine 270 a.a. HOXA5 protein, only the 1.8 kb form is translated into the protein, indicative of its essential role in Hoxa5 gene function. The Hoxa6 mutation disrupts the larger transcripts without major phenotypic impact on axial specification in their expression domain. However, Hoxa5-like skeletal anomalies are observed in Hoxa6 mutants and these defects can be explained by the loss of expression of the 1.8 kb transcript. Our data raise the possibility that the larger transcripts may be involved in Hoxa5 gene regulation.Our observation that the Hoxa5 larger transcripts possess a developmentally-regulated expression combined to the increasing sum of data on the role of long noncoding RNAs in transcriptional regulation suggest that the Hoxa5 larger transcripts may participate in the control of Hox gene expression

A Pregnancy and Childhood Epigenetics Consortium (PACE) meta-analysis highlights potential relationships between birth order and neonatal blood DNA methylation.

Higher birth order is associated with altered risk of many disease states. Changes in placentation and exposures to in utero growth factors with successive pregnancies may impact later life disease risk via persistent DNA methylation alterations. We investigated birth order with Illumina DNA methylation array data in each of 16 birth cohorts (8164 newborns) with European, African, and Latino ancestries from the Pregnancy and Childhood Epigenetics Consortium. Meta-analyzed data demonstrated systematic DNA methylation variation in 341 CpGs (FDR adjusted P < 0.05) and 1107 regions. Forty CpGs were located within known quantitative trait loci for gene expression traits in blood, and trait enrichment analysis suggested a strong association with immune-related, transcriptional control, and blood pressure regulation phenotypes. Decreasing fertility rates worldwide with the concomitant increased proportion of first-born children highlights a potential reflection of birth order-related epigenomic states on changing disease incidence trends

Differential growth patterns of the abdominal aorta and vertebrae during childhood

The adult vertebral level of the splanchnic branches of the abdominal aorta relies on a complex series of fusion and regression steps during embryological development, such that variation is common. Little is known however regarding the anatomy of the abdominal aorta in children. This study aimed to investigate the spatial relationship between the abdominal aorta and the vertebral column during childhood development to inform clinical management of pediatric patients. Retrospective multislice computed tomography abdominopelvic angiograms of children aged neonate to 19 years (n = 232) were used to examine vertebral levels of the celiac trunk (CoT), superior mesenteric artery (SMA), inferior mesenteric artery (IMA), and aortic bifurcation (AB) using multiplanar formatting views in OsiriX. The abdominal aorta length, AB angle, and displacement of the aorta from the midline were quantified with the effect of age and sex analyzed using multinomial logistic regression and general linear models. The most frequent origins of CoT, SMA, IMA, and AB were T12, L1, L3, and L4, respectively, with significant variation in vertebral level for each vessel. SMA level was significantly more proximal with age, and CoT and AB demonstrated marked sex differences in vertebral level. As the age of the child increased, AB angle decreased, aortic displacement increased, and the length of the abdominal aorta increased at a slower velocity to the vertebral column (P < 0.001). Our study highlights the variation of the location and geometry of the abdominal aorta in children; this knowledge will positively impact pediatric surgical approaches and endovascular procedures. Clin. Anat. 32:783–793, 2019.</p

Fostering Social Interaction in Playful Cities

This paper describes different types of activities/challenges designed for social interaction, while discussing the performance of such challenges using the mobile digital game “Secrets of the South” (http://secretsofthesouth.tbm.tudelft.nl/, Secrets of the South). The game was played as part of a scientific meeting, with participants from 25 to 62 years of age and a varying degree of cultural differences. The presentation and discussion of the results of the gameplay provide insights on the appropriateness of the different challenges for social interaction in a playful city. Directions for future work for such challenge designs are presented.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.System Engineerin