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RISS 인기검색어
- 검색키워드
- 저자 : Lipovsek, Saš (검색결과 2 건)
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Lipovsek, Marcela,Im, Gi Jung,Franchini, Luc?a F,Pisciottano, Francisco,Katz, Eleonora,Fuchs, Paul Albert,Elgoyhen, Ana Bel?n National Academy of Sciences 2012 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.109 No.11
<P>The α9 and α10 cholinergic nicotinic receptor subunits assemble to form the receptor that mediates efferent inhibition of hair cell function within the auditory sensory organ, a mechanism thought to modulate the dynamic range of hearing. In contrast to all nicotinic receptors, which serve excitatory neurotransmission, the activation of α9α10 produces hyperpolarization of hair cells. An evolutionary analysis has shown that the α10 subunit exhibits signatures of positive selection only along the mammalian lineage, strongly suggesting the acquisition of a unique function. To establish whether mammalian α9α10 receptors have acquired distinct functional properties as a consequence of this evolutionary pressure, we compared the properties of rat and chicken recombinant and native α9α10 receptors. Our main finding in the present work is that, in contrast to the high (pCa(2+)/pMonovalents 10) Ca(2+) permeability reported for rat α9α10 receptors, recombinant and native chicken α9α10 receptors have a much lower permeability (2) to this cation, comparable to that of neuronal α4β2 receptors. Moreover, we show that, in contrast to α10, α7 as well as α4 and β2 nicotinic subunits are under purifying selection in vertebrates, consistent with the conserved Ca(2+) permeability reported across species. These results have important consequences for the activation of signaling cascades that lead to hyperpolarization of hair cells after α9α10 gating at the cholinergic-hair cell synapse. In addition, they suggest that high Ca(2+) permeability of the α9α10 cholinergic nicotinic receptor might have evolved together with other features that have given the mammalian ear an expanded high-frequency sensitivity.</P>
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Donor Islet Endothelial Cells in Pancreatic Islet Revascularization
Nyqvist, Daniel,Speier, Stephan,Rodriguez-Diaz, Rayner,Molano, R. Damaris,Lipovsek, Saš,a,Rupnik, Marjan,Dicker, Andrea,Ilegems, Erwin,Zahr-Akrawi, Elsie,Molina, Judith,Lopez-Cabeza, Maite,Villat American Diabetes Association 2011 Diabetes Vol.60 No.10
<P><B>OBJECTIVE</B></P><P>Freshly isolated pancreatic islets contain, in contrast to cultured islets, intraislet endothelial cells (ECs), which can contribute to the formation of functional blood vessels after transplantation. We have characterized how donor islet endothelial cells (DIECs) may contribute to the revascularization rate, vascular density, and endocrine graft function after transplantation of freshly isolated and cultured islets.</P><P><B>RESEARCH DESIGN AND METHODS</B></P><P>Freshly isolated and cultured islets were transplanted under the kidney capsule and into the anterior chamber of the eye. Intravital laser scanning microscopy was used to monitor the revascularization process and DIECs in intact grafts. The grafts’ metabolic function was examined by reversal of diabetes, and the ultrastructural morphology by transmission electron microscopy.</P><P><B>RESULTS</B></P><P>DIECs significantly contributed to the vasculature of fresh islet grafts, assessed up to 5 months after transplantation, but were hardly detected in cultured islet grafts. Early participation of DIECs in the revascularization process correlated with a higher revascularization rate of freshly isolated islets compared with cultured islets. However, after complete revascularization, the vascular density was similar in the two groups, and host ECs gained morphological features resembling the endogenous islet vasculature. Surprisingly, grafts originating from cultured islets reversed diabetes more rapidly than those originating from fresh islets.</P><P><B>CONCLUSIONS</B></P><P>In summary, DIECs contributed to the revascularization of fresh, but not cultured, islets by participating in early processes of vessel formation and persisting in the vasculature over long periods of time. However, the DIECs did not increase the vascular density or improve the endocrine function of the grafts.</P>
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