Investigating the influence of body movements on children's mental arithmetic performance.

Several lines of research have demonstrated spatial-numerical associations in both adults and children, which are thought to be based on a spatial representation of numerical information in the form of a mental number line. The acquisition of increasingly precise mental number line representations is assumed to support arithmetic learning in children. It is further suggested that sensorimotor experiences shape the development of number concepts and arithmetic learning, and that mental arithmetic can be characterized as "motion along a path" and might constitute shifts in attention along the mental number line. The present study investigated whether movements in physical space influence mental arithmetic in primary school children, and whether the expected effect depends on concurrency of body movements and mental arithmetic. After turning their body towards the left or right, 48 children aged 8 to 10 years solved simple subtraction and addition problems. Meanwhile, they either walked or stood still and looked towards the respective direction. We report a congruency effect between body orientation and operation type, i.e., higher performance for the combinations leftward orientation and subtraction and rightward orientation and addition. We found no significant difference between walking and looking conditions. The present results suggest that mental arithmetic in children is influenced by preceding sensorimotor cues and not necessarily by concurrent body movements.

Children's spatial language skills predict their verbal number skills: A longitudinal study.

The process of number symbolization is assumed to be critically influenced by the acquisition of so-called verbal number skills (e.g., verbally reciting the number chain and naming Arabic numerals). For the acquisition of these verbal number skills, verbal and visuospatial skills are discussed as contributing factors. In this context, children's verbal number skills have been found to be associated with their concurrent spatial language skills such as mastery of verbal descriptions of spatial position (e.g., in front of, behind). In a longitudinal study with three measurement times (T1, T2, T3) at an interval of about 6 months, we evaluated the predictive role of preschool children's (mean age at T1: 3 years and 10 months) spatial language skills for the acquisition of verbal number skills. Children's spatial language skills at T2 significantly predicted their verbal number skills at T3, when controlling for influences of important covariates such as vocabulary knowledge. In addition, further analyses replicated previous results indicating that children's spatial language skills at T2 were associated with their verbal number skills at T2. Exploratory analyses further revealed that children's verbal number skills at T1 predict their spatial language at T2. Results suggests that better spatial language skills at the age of 4 years facilitate the future acquisition of verbal number skills.

Children's use of egocentric reference frames in spatial language is related to their numerical magnitude understanding.

Numerical magnitude information is assumed to be spatially represented in the form of a mental number line defined with respect to a body-centred, egocentric frame of reference. In this context, spatial language skills such as mastery of verbal descriptions of spatial position (e.g., in front of, behind, to the right/left) have been proposed to be relevant for grasping spatial relations between numerical magnitudes on the mental number line. We examined 4- to 5-year-old's spatial language skills in tasks that allow responses in egocentric and allocentric frames of reference, as well as their relative understanding of numerical magnitude (assessed by a number word comparison task). In addition, we evaluated influences of children's absolute understanding of numerical magnitude assessed by their number word comprehension (montring different numbers using their fingers) and of their knowledge on numerical sequences (determining predecessors and successors as well as identifying missing dice patterns of a series). Results indicated that when considering responses that corresponded to the egocentric perspective, children's spatial language was associated significantly with their relative numerical magnitude understanding, even after controlling for covariates, such as children's SES, mental rotation skills, and also absolute magnitude understanding or knowledge on numerical sequences. This suggests that the use of egocentric reference frames in spatial language may facilitate spatial representation of numbers along a mental number line and thus seem important for preschoolers' relative understanding of numerical magnitude.

Critical Role of TGF-ß and IL-2 Receptor Signaling in Foxp3 Induction by an Inhibitor of DNA Methylation.

Under physiological conditions, CD4+ regulatory T (Treg) cells expressing the transcription factor Foxp3 are generated in the thymus [thymus-derived Foxp3+ Treg (tTregs) cells] and extrathymically at peripheral sites [peripherally induced Foxp3+ Treg (pTreg) cell], and both developmental subsets play non-redundant roles in maintaining self-tolerance throughout life. In addition, a variety of experimental in vitro and in vivo modalities can extrathymically elicit a Foxp3+ Treg cell phenotype in peripheral CD4+Foxp3- T cells, which has attracted much interest as an approach toward cell-based therapy in clinical settings of undesired immune responses. A particularly notable example is the in vitro induction of Foxp3 expression and Treg cell activity (iTreg cells) in initially naive CD4+Foxp3- T cells through T cell receptor (TCR) and IL-2R ligation, in the presence of exogenous TGF-ß. Clinical application of Foxp3+ iTreg cells has been hampered by the fact that TGF-ß-driven Foxp3 induction is not sufficient to fully recapitulate the epigenetic and transcriptional signature of in vivo induced Foxp3+ tTreg and pTreg cells, which includes the failure to imprint iTreg cells with stable Foxp3 expression. This hurdle can be potentially overcome by pharmacological interference with DNA methyltransferase activity and CpG methylation [e.g., by the cytosine nucleoside analog 5-aza-2'-deoxycytidine (5-aza-dC)] to stabilize TGF-ß-induced Foxp3 expression and to promote a Foxp3+ iTreg cell phenotype even in the absence of added TGF-ß. However, the molecular mechanisms of 5-aza-dC-mediated Foxp3+ iTreg cell generation have remained incompletely understood. Here, we show that in the absence of exogenously added TGF-ß and IL-2, efficient 5-aza-dC-mediated Foxp3+ iTreg cell generation from TCR-stimulated CD4+Foxp3- T cells is critically dependent on TGF-ßR and IL-2R signaling and that this process is driven by TGF-ß and IL-2, which could either be FCS derived or produced by T cells on TCR stimulation. Overall, these findings contribute to our understanding of the molecular mechanisms underlying the process of Foxp3 induction and may provide a rational basis for generating phenotypically and functionally stable iTreg cells.