Children's exploration of the concepts of home and belonging: Capturing views from five European countries.

Understanding one’s sense of belonging is a central part of identity formation and self-awareness, feeling safe somewhere, with specific people is identified as a basic human need. This paper explores the ideas of children from three age groups in five different European as they discussed the concepts of ‘home’ and ‘belonging’. Findings showed that the children’s ideas could be organised into six interrelated aspects: Spatiality, Materiality, Multiplicity, Social Relations, Affect, and Dislocation. Whilst there were differences in the ways that the children conceptualised home across the classes, even the youngest children were able to describe their ideas using metaphors and abstract concepts, and they agreed that a home was more than just a buildin

LuxRep: a technical replicate-aware method for bisulfite sequencing data analysis

Background: DNA methylation is commonly measured using bisulfite sequencing (BS-seq). The quality of a BS-seq library is measured by its bisulfite conversion efficiency. Libraries with low conversion rates are typically excluded from analysis resulting in reduced coverage and increased costs.Results: We have developed a probabilistic method and software, LuxRep, that implements a general linear model and simultaneously accounts for technical replicates (libraries from the same biological sample) from different bisulfite-converted DNA libraries. Using simulations and actual DNA methylation data, we show that including technical replicates with low bisulfite conversion rates generates more accurate estimates of methylation levels and differentially methylated sites. Moreover, using variational inference speeds up computation time necessary for whole genome analysis.Conclusions: In this work we show that taking into account technical replicates (i.e. libraries) of BS-seq data of varying bisulfite conversion rates, with their corresponding experimental parameters, improves methylation level estimation and differential methylation detection.</p

Neuroimaging and neurological outcome of children with acute encephalitis

Aim: To investigate the severity of acute phase magnetic resonance imaging (MRI) findings and severity of acute illness as risk factors for disability after recovery from encephalitis.Method: Children  with  encephalitis  (n  =  98;  median  age  6  years  10  months,  inter-quartile  range  3  years–11  years  6  months;  59  males,  39  females)  treated  in  Turku  University Hospital during the years 1995 to 2016 were identified in this retrospec-tive cohort study. The acute phase (1  year  from  discharge)  follow-up  was  as-sessed from medical records using the Glasgow Outcome Scale.Results: Long-term recovery was poor in 24 of 82 (29%) children with follow-up data. Two children died, eight had severe disability, and 14 had moderate disability. Acute phase MRI was available for re-evaluation from 74 of 82 patients with follow-up data. The increasing severity of MRI findings was associated with need for ventilator ther-apy and with poor recovery.Interpretation: The risk for poor recovery in paediatric encephalitis is high, and it is associated with the severity of MRI findings.</p

Associations of age and sex with brain volumes and asymmetry in 2–5-week-old infants

Information on normal brain structure and development facilitates the recognition of abnormal developmental trajectories and thus needs to be studied in more detail. We imaged 68 healthy infants aged 2–5 weeks with high-resolution structural MRI (magnetic resonance imaging) and investigated hemispheric asymmetry as well as the associations of various total and lobar brain volumes with infant age and sex. We found similar hemispheric asymmetry in both sexes, seen as larger volumes of the right temporal lobe, and of the left parietal and occipital lobes. The degree of asymmetry did not vary with age. Regardless of controlling for gestational age, gray and white matter had different age-related growth patterns. This is a reflection of gray matter growth being greater in the first years, while white matter growth extends into early adulthood. Sex-dependent differences were seen in gray matter as larger regional absolute volumes in males and as larger regional relative volumes in females. Our results are in line with previous studies and expand our understanding of infant brain development.</p

Expression profiles of long non-coding RNAs located in autoimmune disease-associated regions reveal immune cell-type specificity

Background: Although genome-wide association studies (GWAS) have identified hundreds of variants associated with a risk for autoimmune and immune-related disorders (AID), our understanding of the disease mechanisms is still limited. In particular, more than 90% of the risk variants lie in non-coding regions, and almost 10% of these map to long non-coding RNA transcripts (lncRNAs). lncRNAs are known to show more cell-type specificity than protein-coding genes. Methods: We aimed to characterize lncRNAs and protein-coding genes located in loci associated with nine AIDs which have been well-defined by Immunochip analysis and by transcriptome analysis across seven populations of peripheral blood leukocytes (granulocytes, monocytes, natural killer (NK) cells, B cells, memory T cells, naive CD4(+) and naive CD8(+) T cells) and four populations of cord blood-derived T-helper cells (precursor, primary, and polarized (Th1, Th2) T-helper cells). Results: We show that lncRNAs mapping to loci shared between AID are significantly enriched in immune cell types compared to lncRNAs from the whole genome (a <0.005). We were not able to prioritize single cell types relevant for specific diseases, but we observed five different cell types enriched (a <0.005) in five AID (NK cells for inflammatory bowel disease, juvenile idiopathic arthritis, primary biliary cirrhosis, and psoriasis; memory T and CD8(+) T cells in juvenile idiopathic arthritis, primary biliary cirrhosis, psoriasis, and rheumatoid arthritis; Th0 and Th2 cells for inflammatory bowel disease, juvenile idiopathic arthritis, primary biliary cirrhosis, psoriasis, and rheumatoid arthritis). Furthermore, we show that co-expression analyses of lncRNAs and protein-coding genes can predict the signaling pathways in which these AID-associated lncRNAs are involved. Conclusions: The observed enrichment of lncRNA transcripts in AID loci implies lncRNAs play an important role in AID etiology and suggests that lncRNA genes should be studied in more detail to interpret GWAS findings correctly. The co-expression results strongly support a model in which the lncRNA and protein-coding genes function together in the same pathways

Development and pilot testing of PHARAO—a decision support system for pharmacological risk assessment in the elderly

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Sex-specific association between infant caudate volumes and a polygenic risk score for major depressive disorder

Polygenic risk scores for major depressive disorder (PRS-MDD) have been identified in large genome-wide association studies, and recent findings suggest that PRS-MDD might interact with environmental risk factors to shape human limbic brain development as early as in the prenatal period. Striatal structures are crucially involved in depression; however, the association of PRS-MDD with infant striatal volumes is yet unknown. In this study, 105 Finnish mother-infant dyads (44 female, 11-54 days old) were investigated to reveal how infant PRS-MDD is associated with infant dorsal striatal volumes (caudate, putamen) and whether PRS-MDD interacts with prenatal maternal depressive symptoms (Edinburgh Postnatal Depression Scale, gestational weeks 14, 24, 34) on infant striatal volumes. A robust sex-specific main effect of PRS-MDD on bilateral infant caudate volumes was observed. PRS-MDD were more positively associated with caudate volumes in boys compared to girls. No significant interaction effects of genotype PRS-MDD with the environmental risk factor "prenatal maternal depressive symptoms" (genotype-by-environment interaction) nor significant interaction effects of genotype with prenatal maternal depressive symptoms and sex (genotype-by-environment-by-sex interaction) were found for infant dorsal striatal volumes. Our study showed that a higher PRS-MDD irrespective of prenatal exposure to maternal depressive symptoms is associated with smaller bilateral caudate volumes, an indicator of greater susceptibility to major depressive disorder, in female compared to male infants. This sex-specific polygenic effect might lay the ground for the higher prevalence of depression in women compared to men.Peer reviewe

Genome-wide association study of primary tooth eruption identifies pleiotropic loci associated with height and craniofacial distances

Twin and family studies indicate that the timing of primary tooth eruption is highly heritable, with estimates typically exceeding 80%. To identify variants involved in primary tooth eruption we performed a population based genome-wide association study of ‘age at first tooth’ and ‘number of teeth’ using 5998 and 6609 individuals respectively from the Avon Longitudinal Study of Parents and Children (ALSPAC) and 5403 individuals from the 1966 Northern Finland Birth Cohort (NFBC1966). We tested 2,446,724 SNPs imputed in both studies. Analyses were controlled for the effect of gestational age, sex and age of measurement. Results from the two studies were combined using fixed effects inverse variance meta-analysis. We identified a total of fifteen independent loci, with ten loci reaching genome-wide significance (p<5x10−8) for ‘age at first tooth’ and eleven loci for ‘number of teeth’. Together these associations explain 6.06% of the variation in ‘age of first tooth’ and 4.76% of the variation in ‘number of teeth’. The identified loci included eight previously unidentified loci, some containing genes known to play a role in tooth and other developmental pathways, including a SNP in the protein-coding region of BMP4 (rs17563, P= 9.080x10−17). Three of these loci, containing the genes HMGA2, AJUBA and ADK, also showed evidence of association with craniofacial distances, particularly those indexing facial width. Our results suggest that the genome-wide association approach is a powerful strategy for detecting variants involved in tooth eruption, and potentially craniofacial growth and more generally organ development

Dynamic modeling of gene expression in prokaryotes: application to glucose-lactose diauxie in Escherichia coli

Coexpression of genes or, more generally, similarity in the expression profiles poses an unsurmountable obstacle to inferring the gene regulatory network (GRN) based solely on data from DNA microarray time series. Clustering of genes with similar expression profiles allows for a course-grained view of the GRN and a probabilistic determination of the connectivity among the clusters. We present a model for the temporal evolution of a gene cluster network which takes into account interactions of gene products with genes and, through a non-constant degradation rate, with other gene products. The number of model parameters is reduced by using polynomial functions to interpolate temporal data points. In this manner, the task of parameter estimation is reduced to a system of linear algebraic equations, thus making the computation time shorter by orders of magnitude. To eliminate irrelevant networks, we test each GRN for stability with respect to parameter variations, and impose restrictions on its behavior near the steady state. We apply our model and methods to DNA microarray time series' data collected on Escherichia coli during glucose-lactose diauxie and infer the most probable cluster network for different phases of the experiment.Comment: 20 pages, 4 figures; Systems and Synthetic Biology 5 (2011