Endocardial cell epithelial-mesenchymal transformation requires Type III TGFβ receptor interaction with GIPC

An early event in heart valve formation is the epithelial-mesenchymal transformation (EMT) of a subpopulation of endothelial cells in specific regions of the heart tube, the endocardial cushions. The Type III TGFβ receptor (TGFβR3) is required for TGFβ2- or BMP-2-stimulated EMT in atrioventricular endocardial cushion (AVC) explants in vitro but the mediators downstream of TGFβR3 are not well described. Using AVC and ventricular explants as an in vitro assay, we found an absolute requirement for specific TGFβR3 cytoplasmic residues, GAIP-interacting protein, C terminus (GIPC), and specific Activin Receptor-Like Kinases (ALK)s for TGFβR3-mediated EMT when stimulated by TGFβ2 or BMP-2. The introduction of TGFβR3 into nontransforming ventricular endocardial cells, followed by the addition of either TGFβ2 or BMP-2, results in EMT. TGFβR3 lacking the entire cytoplasmic domain, or only the 3C-terminal amino acids that are required to bind GIPC, fails to support EMT in response to TGFβ2 or BMP-2. Overexpression of GIPC in AVC endocardial cells enhanced EMT while siRNA-mediated silencing of GIPC in ventricular cells overexpressing TGFβR3 significantly inhibited EMT. Targeting of specific ALKs by siRNA revealed that TGFβR3-mediated EMT requires ALK2 and ALK3, in addition to ALK5, but not ALK4 or ALK6. Taken together, these data identify GIPC, ALK2, ALK3, and ALK5 as signaling components required for TGFβR3-mediated endothelial cell EMT.     

Variability of a dynamic visual signal: the fiddler crab claw-waving display

Fiddler crabs use elaborate, species-specific claw-waving displays to communicate with rivals and mates. However, detailed comparative studies of fiddler crab signal structure and structural variations are lacking. This paper provides an analysis of the claw-waving displays of seven Australian species of fiddler crab, Uca mjoebergi, U. perplexa, U. polita, U. seismella, U. signata, U. elegans and U. vomeris. We used digital video to record and analyse the fine-scale spatiotemporal properties of these movement-based visual signals. We found that the structure and timing of the displays is species-specific, exhibiting inter-specific differences that follow phylogenetic relationships. The displays showed intra-specific variation according to individual identity, geographic location and fine-scale behavioural context. The observed differences and variations are discussed in the light of the evolutionary forces that may shape their design.     

Generation of oligodendroglial progenitors from neural stem cells

To understand how the differentiation of stem cells to oligodendroglial progenitors is regulated, we established cultures of neural stem cells from neonatal rat striatum in the presence of epidermal growth factor (EGF) as free-floating neurospheres that were then exposed to an increasing amount of B104 cell-conditioned medium (B104CM). The resultant cells proliferated in response to B104CM but no longer to EGF. In vitro analysis and transplantation studies indicated that these cells were committed to the oligodendroglial lineage, and they were thus referred to as oligospheres. Further characterization of their expression of early markers, cell cycle, migration, and self-renewal suggests that they were pre-O2A progenitors. RT-PCR analysis indicated that the oligosphere cells expressed mRNAs of platelet-derived growth factor α receptor in addition to fibroblast growth factor receptor but not EGF receptor; the latter two receptor mRNAs were expressed by neurosphere cells. Thus, the progression of stem cells to oligodendroglial progenitors is likely induced by factors in B104CM.     

外源腐胺对石刁柏愈伤组织胚性能力的影响

石刁柏胚性愈伤组织继代过程中,添加浓度为10 mg·L^-1的外源腐胺能有效地保持愈伤组织的胚胎发生能力,并减少愈伤组织的褐化,但不能提高愈伤组织的体细胞胚的诱导率.腐胺处理过的胚性愈伤组织的内源腐胺含量明显提高.这可能是外源腐胺保持细胞胚性、降低褐化程度的原因.     

Copper complex derived from <Emphasis Type="Italic">S</Emphasis>-benzyldithiocarbazate and 3-acetylcoumarin induced apoptosis in breast cancer cell

Copper complexes have been widely studied for the anti-tumour application as cancer cells are reported to take up greater amounts of copper than normal cells. Preliminary study revealed that the newly synthesised copper complex [Cu(SBCM)₂] displayed marked anti-proliferative towards triple-negative MDA-MB-231 breast cancer cells. Therefore, Cu(SBCM)₂ has great potential to be developed as an agent for the management of breast cancer. The present study was carried out to investigate the mode of cell death induced by Cu(SBCM)₂ towards MDA-MB-231 breast cancer cells. The inhibitory and morphological changes of MDA-MB-231 cells treated with Cu(SBCM)₂ was determined by using MTT assay and inverted light microscope, respectively. The safety profile of Cu(SBCM)₂ was also evaluated towards human dermal fibroblast (HDF) normal cells. Confirmation of apoptosis and cell cycle arrest were determined by flow cytometry analysis. The expression of p53, Bax, Bcl-2 and MMP2 protein were detected with western blot analysis. Cu(SBCM)₂ significantly inhibited the growth of MDA-MB-231 cells in a dose-dependent manner with GI₅₀ 18.7?±?3.06 µM. Indeed, Cu(SBCM)₂ was less toxic towards HDF normal cells with GI₅₀ 31.8?±?4.0 µM. Morphological study revealed that Cu(SBCM)₂-treated MDA-MB-231 cells experienced cellular shrinkage, membrane blebbing, chromatin condensation and formation of apoptotic bodies, suggesting that Cu(SBCM)₂ induced apoptosis in the cells, which was confirmed by Annexin-V/PI flow cytometry analysis. It was also found that Cu(SBCM)₂ induced G₂/M phase cell cycle arrest towards MDA-MB-231 cells. The induction of apoptosis and cell cycle arrest in the present study is possibly due to the down-regulation of the mutant p53 and MMP2 protein. In conclusion, Cu(SBCM)₂ can be developed as a targeted therapy for the treatment of triple-negative breast cancer.