Myelodysplasia syndrome 1 (MDS1) and Ecotropic viral integration site 1 (EVI1) complex (MECOM) locus encode multiple isoforms of the EVI1 protein that are essential for normal vertebrate development and when inappropr...Myelodysplasia syndrome 1 (MDS1) and Ecotropic viral integration site 1 (EVI1) complex (MECOM) locus encode multiple isoforms of the EVI1 protein that are essential for normal vertebrate development and when inappropriately expressed play a significant role in malignancy and in particular leukaemias. However, the function of individual EVI1 isoforms is not fully understood. Recently, EVI1 or PRDM3, which is structurally closely related to the brown adipose tissue determining factor PRDM16, was shown to be required for differentiation of adipocytes. In this study, we show that 3T3-L1 preadipocytes sustain expression of all Evi1 isoforms examined, including Mds1-Evi1, Evi1FL, Evi1Δ324, Evi1FL + 9 and Evi1Δ105 throughout the adipogenesis differentiation programme. We also show that differentiation markers are enhanced by enforced expression of either Evi1, Evi1FL + 9 or Evi1Δ105 isoforms. Interestingly 3T3-L1 differentiation markers are also moderately enhanced by enforced expression of Evi1Δ324, which lacks part of the N-ter-minal zinc finger domain (ZF1), demonstrating a biological activity for this particular isoform. Enforced expression of an Evi1 mutant lacking C-terminal binding protein (CtBP) co-repressor protein binding activity fails to stimulate 3T3-L1 differentiation markers and may have dominant negative activity, causing partial inhibition of this developmental programme. These studies show that multiple EVI1 isoforms are expressed in adipocytes and can stimulate adipogenic markers in a manner that is partially independent of the ZF1 DNA binding domain but fully dependent upon interaction with co-repressor CtBP proteins.展开更多
Permanent damage to hair cells(HCs)is the leading cause of sensory deafness.Supporting cells(SCs)are essential in the restoration of hearing in mammals because they can proliferate and differentiate to HCs.MDS1 and EV...Permanent damage to hair cells(HCs)is the leading cause of sensory deafness.Supporting cells(SCs)are essential in the restoration of hearing in mammals because they can proliferate and differentiate to HCs.MDS1 and EVI1 complex locus(MECOM)is vital in early development and cell differentiation and regulates the TGF-βsignaling pathway to adapt to pathophysiological events,such as hematopoietic proliferation,differentiation and cells death.In addition,MECOM plays an essential role in neurogenesis and craniofacial development.However,the role of MECOM in the development of cochlea and its way to regulate related signaling are not fully understood.To address this problem,this study examined the expression of MECOM during the development of cochlea and observed a significant increase of MECOM at the key point of auditory epithelial morphogenesis,indicating that MECOM may have a vital function in the formation of cochlea and regeneration of HCs.Meanwhile,we tried to explore the possible effect and potential mechanism of MECOM in SC proliferation and HC regeneration.Findings from this study indicate that overexpression of MECOM markedly increases the proliferation of SCs in the inner ear,and the expression of Smad3 and Cdkn2b related to TGF signaling is significantly down-regulated,corresponding to the overexpression of MECOM.Collectively,these data may provide an explanation of the vital function of MECOM in SC proliferation and trans-differentiation into HCs,as well as its regulation.The interaction between MECOM,Wnt,Notch and the TGF-βsignaling may provide a feasible approach to induce the regeneration of HCs.展开更多
After socio-political breakthrough in 1989 foreign companies entered Polish media market. Firstly, investors appeared in the press sector, later on in the electronic media. One of the first groups presented in Poland ...After socio-political breakthrough in 1989 foreign companies entered Polish media market. Firstly, investors appeared in the press sector, later on in the electronic media. One of the first groups presented in Poland was Orkla Media. The Norwegians launched a brand new regional daily. After subsequent failure they changed the pattern of business activity. When in 2006 Mecom bought out Orkla＇s shares, a new era began. The British fund was mainly interested in making their assets more profitable. The biggest shareholder of the regional press sector, however, is still Verlagsgruppe Passau （VGP）. The German group appeared in 1993, in disguise of a Swiss company and next year took over eight regional dailies. In due course, VGP bought out a couple of more regional titles and became the leader of this sector of the market. Although the Germans were competing against the Norwegians and the Brits, they showed a different style of managing their assets. The author attempts to describe different patterns of business strategy in the press sector in Poland, examining each investor＇s behavior and the results of their efforts. This can lead to conclusions about the past activities as well as to predictions about the future of the market.展开更多
文摘Myelodysplasia syndrome 1 (MDS1) and Ecotropic viral integration site 1 (EVI1) complex (MECOM) locus encode multiple isoforms of the EVI1 protein that are essential for normal vertebrate development and when inappropriately expressed play a significant role in malignancy and in particular leukaemias. However, the function of individual EVI1 isoforms is not fully understood. Recently, EVI1 or PRDM3, which is structurally closely related to the brown adipose tissue determining factor PRDM16, was shown to be required for differentiation of adipocytes. In this study, we show that 3T3-L1 preadipocytes sustain expression of all Evi1 isoforms examined, including Mds1-Evi1, Evi1FL, Evi1Δ324, Evi1FL + 9 and Evi1Δ105 throughout the adipogenesis differentiation programme. We also show that differentiation markers are enhanced by enforced expression of either Evi1, Evi1FL + 9 or Evi1Δ105 isoforms. Interestingly 3T3-L1 differentiation markers are also moderately enhanced by enforced expression of Evi1Δ324, which lacks part of the N-ter-minal zinc finger domain (ZF1), demonstrating a biological activity for this particular isoform. Enforced expression of an Evi1 mutant lacking C-terminal binding protein (CtBP) co-repressor protein binding activity fails to stimulate 3T3-L1 differentiation markers and may have dominant negative activity, causing partial inhibition of this developmental programme. These studies show that multiple EVI1 isoforms are expressed in adipocytes and can stimulate adipogenic markers in a manner that is partially independent of the ZF1 DNA binding domain but fully dependent upon interaction with co-repressor CtBP proteins.
基金was supported by the Chinese National Natural Science Foundation of China(grant number 81371089)the Research Project of Wannan Medical College(grant number WK202122).
文摘Permanent damage to hair cells(HCs)is the leading cause of sensory deafness.Supporting cells(SCs)are essential in the restoration of hearing in mammals because they can proliferate and differentiate to HCs.MDS1 and EVI1 complex locus(MECOM)is vital in early development and cell differentiation and regulates the TGF-βsignaling pathway to adapt to pathophysiological events,such as hematopoietic proliferation,differentiation and cells death.In addition,MECOM plays an essential role in neurogenesis and craniofacial development.However,the role of MECOM in the development of cochlea and its way to regulate related signaling are not fully understood.To address this problem,this study examined the expression of MECOM during the development of cochlea and observed a significant increase of MECOM at the key point of auditory epithelial morphogenesis,indicating that MECOM may have a vital function in the formation of cochlea and regeneration of HCs.Meanwhile,we tried to explore the possible effect and potential mechanism of MECOM in SC proliferation and HC regeneration.Findings from this study indicate that overexpression of MECOM markedly increases the proliferation of SCs in the inner ear,and the expression of Smad3 and Cdkn2b related to TGF signaling is significantly down-regulated,corresponding to the overexpression of MECOM.Collectively,these data may provide an explanation of the vital function of MECOM in SC proliferation and trans-differentiation into HCs,as well as its regulation.The interaction between MECOM,Wnt,Notch and the TGF-βsignaling may provide a feasible approach to induce the regeneration of HCs.
文摘After socio-political breakthrough in 1989 foreign companies entered Polish media market. Firstly, investors appeared in the press sector, later on in the electronic media. One of the first groups presented in Poland was Orkla Media. The Norwegians launched a brand new regional daily. After subsequent failure they changed the pattern of business activity. When in 2006 Mecom bought out Orkla＇s shares, a new era began. The British fund was mainly interested in making their assets more profitable. The biggest shareholder of the regional press sector, however, is still Verlagsgruppe Passau （VGP）. The German group appeared in 1993, in disguise of a Swiss company and next year took over eight regional dailies. In due course, VGP bought out a couple of more regional titles and became the leader of this sector of the market. Although the Germans were competing against the Norwegians and the Brits, they showed a different style of managing their assets. The author attempts to describe different patterns of business strategy in the press sector in Poland, examining each investor＇s behavior and the results of their efforts. This can lead to conclusions about the past activities as well as to predictions about the future of the market.
