Epithelial-mesenchymal (EMT) and mesenchymal-epithelial (MET) transitions occur in the development of human tumorigenesis and are part of the natural history of the process to adapt to the changing microenvironment. In this setting, the miR-200 family is recognized as a master regulator of the epithelial phenotype by targeting ZEB1 and ZEB2, two important transcriptional repressors of the cell adherence (E-cadherin) and polarity (CRB3 and LGL2) genes. Recently, the putative DNA methylation associated inactivation of various miR-200 members has been described in cancer. Herein, we show that the miR-200ba429 and miR-200c141 transcripts undergo a dynamic epigenetic regulation linked to EMT or MET phenotypes in tumor progression. The 5′-CpG islands of both miR-200 loci were found unmethylated and coupled to the expression of the corresponding miRNAs in human cancer cell lines with epithelial features, such as low levels of ZEB1/ZEB2 and high expression of E-cadherin, CRB3 and LGL2, while CpG island hypermethylation-associated silencing was observed in transformed cells with mesenchymal characteristics. The recovery of miR-200ba429 and miR-200c141 expression by stable transfection in the hypermethylated cells restored the epithelial markers and inhibited migration in cell culture and tumoral growth and metastasis formation in nude mice. We also discovered, using both cell culture and animal models, that the miR-200 epigenetic silencing is not an static and fixed process but it can be shifted to hypermethylated or unmethylated 5′-CpG island status corresponding to the EMT and MET phenotypes, respectively. In fact, careful laser microdissection in human primary colorectal tumorigenesis unveiled that in normal colon mucosa crypts (epithelia) and stroma (mesenchyma) already are unmethylated and methylated at these loci, respectively; and that the colorectal tumors undergo selective miR-200 hypermethylation of their epithelial component. These findings indicate that the epigenetic silencing plasticity of the miR-200 family contributes to the evolving and adapting phenotypes of human tumors.
Previous research has proposed that team coordination is based on shared knowledge of the performance context, responsible for linking teammates' mental representations for collective, internalized action solutions. However, this representational approach raises many questions including: how do individual schemata of team members become reformulated together? How much time does it take for this collective cognitive process to occur? How do different cues perceived by different individuals sustain a general shared mental representation? This representational approach is challenged by an ecological dynamics perspective of shared knowledge in team coordination. We argue that the traditional shared knowledge assumption is predicated on 'knowledge about' the environment, which can be used to share knowledge and influence intentions of others prior to competition. Rather, during competitive performance, the control of action by perceiving surrounding informational constraints is expressed in 'knowledge of' the environment. This crucial distinction emphasizes perception of shared affordances (for others and of others) as the main communication channel between team members during team coordination tasks. From this perspective, the emergence of coordinated behaviours in sports teams is based on the formation of interpersonal synergies between players resulting from collective actions predicated on shared affordances.
The aims of this study were: (1) to observe participation in moderate-to-vigorous physical activity (MVPA) during school recess periods; (2) to determine the relative importance of physical activity during recesses to overall daily physical activity; and (3) to examine differences in physical activity between the sexes during unstructured recess periods. The participants were 22 school children (10 boys, 12 girls) aged 8 - 10 years (mean = 8.9, s = 0.7) in the third and fourth grades. Daily totals for the physical activity variables were calculated by summing the values for each hour of 14 h of physical activity measurements (08:00 to 22:00 h). Recess times (minutes) were as follows: morning 10:30 to 11:00 h and afternoon 15:30 to 16:00 h. We did not differences between boys and girls in daily total accelerometer counts or the overall time spent in MVPA. However, girls were significantly (P < 0.05) more involved (38%) in MVPA during recess time than boys (31%). Participation in MVPA during recess contributes significantly more (P < 0.05) for girls (19%) than boys (15%) to the total amount of physical activity suggested by international health-related physical activity guidelines, while the percentage of time engaged in MVPA during recess time at school accounts for a small amount of the daily MVPA (6% for boys and 8% for girls). The results of this study suggest that school recess time is an important setting to promote MVPA and contributes to daily physical activity in young children, especially in girls.
Staff training, recreational equipment, and playground markings are inexpensive, simple ways to increase PA during recess so that children can accumulate minutes of PA to meet the recommended guidelines of 60 minutes per day.
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