EphAs and ephrin-As have been implicated in the morphogenesis of the developing brain. We found that EphA7 and ephrin-A5 are coexpressed in the dorsal midline (DM) of the diencephalon and anterior mesencephalon. Interestingly, programmed cell death (PCD) of the neural epithelial cells normally found in this region was reduced in ephrin-A5/ephrin-A2 dual-deficient embryos. In contrast, in vivo expression of ephrin-A5-Fc or full-length ephrin-A5 strongly induced apoptosis in neural epithelial cells and was accompanied by severe brain malformation during embryonic development. Expression of ephrinA5-Fc correlated with apoptosis of EphA7-expressing cells, whereas null mutation of ephrin-A5 resulted in the converse phenotype. Importantly, null mutation of caspase-3 or endogenous ephrin-A5 attenuated the PCD induced by ectopically overexpressed ephrin-A5. Together, our results suggest that brain region-specific PCD may occur in a region where EphAs cluster with neighboring ephrin-As through cell-cell contact.
Drug resistance to BCR-ABL1 tyrosine kinase inhibitor (TKI) and disease progression to blast crisis (BC) are major clinical problems in chronic myeloid leukemia (CML); however, underlying mechanisms governing this process remain to be elucidated. Here, we report Cordon-bleu protein-like 1 (Cobll1) as a distinct molecular marker associated with drug resistance as well as progression to BC. In detail, Cobll1 increases IKKγ stability, leading to NF-κB activation and reduction of nilotinib-dependent apoptosis, suggesting Cobll1-mediated NF-κB could be involved in drug resistance. Recently, NF-κB signalling has been highlighted as a core mechanism for chronic phase (CP)-BC progression, stem cell survival and tyrosine kinase inhibitor resistance. We also demonstrated that high expression of Cobll1 confers drug resistance to tyrosine kinase inhibitors in CML cell line as well as patient samples. The analysis of large sets of primary CML samples (n=90) shows that Cobll1 expression is dramatically increased in BC but not in CP, which is correlated with a poor survival rate (P=0.002). Moreover, our studies show that Cobll1 is highly expressed in CD34 primitive stem cell populations, and the zebrafish paralog Cobll1b is important for normal hematopoiesis during embryonic development. Based on these results, we propose that Cobll1 is a novel biomarker and potential therapeutic target for CML-BC.
S77 census sample however, only 568 students participated, the return rate was 90.59%. A 2 page questionnaire consisted of Thai Spielberger's Form (TSF) and socioeconomic status. The TSF measured 2 dimensions namely: emotional and worry. It consisted of 14 measurement variables measured by visual analogue scale. RESULTS: The TSF's internal consistency was detected by Cronbach's Alpha yield r= 0.849. The second year student had the most anxiety score compared to all students (1st to 5th year). Anxiety had a negative correlation to GPAX (r =-0.084, p= 0.047, Pearson's correlation). Hierarchical Stepwise Multiple Regression Analysis was employed to establish academic achievement prediction model by using anxiety, social support and gender as the predictors: GPAX = 0.061 boy/girl-friend + 0.109 friend support *+0.092 anxiety*-0.017 family support-0.008 parents-0.128 gender**. (p-value 0.010, 0.030 and 0.002 respectively) with R-square 0.410 CONCLUSIONS: Gender had the biggest impact on academic achievement and 3 significant predictors of Academic Achievement model were gender, friend support and anxiety.
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