<it>IGF2</it>/<it>H19</it> hypomethylation is tissue, cell, and CpG site dependent and not correlated with body asymmetry in adolescents with Silver-Russell syndrome

<p>Abstract</p> <p>Background</p> <p>Silver-Russell syndrome (SRS) is characterized by severe intrauterine and postnatal growth failure and frequent body asymmetry. Half of the patients with SRS carry a DNA hypomethylation of the imprinting center region 1 (ICR1) of the insulin-like growth factor 2 (<it>IGF2</it>)/<it>H19</it> locus, and the clinical phenotype is most severe in these patients. We aimed to elucidate the epigenetic basis of asymmetry in SRS and the cellular consequences of the ICR1 hypomethylation.</p> <p>Results</p> <p>The ICR1 methylation status was analyzed in blood and in addition in buccal smear probes and cultured fibroblasts obtained from punch biopsies taken from the two body halves of 5 SRS patients and 3 controls. We found that the ICR1 hypomethylation in SRS patients was stronger in blood leukocytes and oral mucosa cells than in fibroblasts. ICR1 CpG sites were affected differently. The severity of hypomethylation was not correlated to body asymmetry. <it>IGF2</it> expression and IGF-II secretion of fibroblasts were not correlated to the degree of ICR1 hypomethylation. SRS fibroblasts responded well to stimulation by recombinant human IGF-I or IGF-II, with proliferation rates comparable with controls. Clonal expansion of primary fibroblasts confirmed the complexity of the cellular mosaicism.</p> <p>Conclusions</p> <p>We conclude that the ICR1 hypomethylation SRS is tissue, cell, and CpG site specific. The correlation of the ICR1 hypomethylation to <it>IGF2</it> and <it>H19</it> expression is not strict, may depend on the investigated tissue, and may become evident only in case of more severe methylation defects. The body asymmetry in juvenile SRS patients is not related to a corresponding ICR1 hypomethylation gradient, rendering more likely an intrauterine origin of asymmetry. Overall, it may be instrumental to consider not only the ICR1 methylation status as decisive for <it>IGF2</it>/<it>H19</it> expression regulation.</p

Testing the effectiveness of mathematical games as a pedagogical tool for children\u27s learning

In an effort to engage children in mathematics learning, many primary teachers use mathematical games and activities. Games have been employed for drill and practice, warm-up activities and rewards. The effectiveness of games as a pedagogical tool requires further examination if games are to be employed for the teaching of mathematical concepts. This paper reports research that compared the effectiveness of non-digital games with non-game but engaging activities as pedagogical tools for promoting mathematical learning. In the classrooms that played games, the effects of adding teacher-led whole class discussion was explored. The research was conducted with 10&ndash;12-year-old children in eight classrooms in three Australian primary schools, using differing instructional approaches to teach multiplication and division of decimals. A quasi-experimental design with pre-test, post-test and delayed post-test was employed, and the effects of the interventions were measured by the children&rsquo;s written test performance. Test results indicated lesser gains in learning in game playing situations versus non-game activities and that teacher-led discussions during and following the game playing did not improve children&rsquo;s learning. The finding that these games did not help children demonstrate a mathematical understanding of concepts under test conditions suggests that educators should carefully consider the application and appropriateness of games before employing them as a vehicle for introducing mathematical concepts