Static and dynamic properties of Single-Chain Magnets with sharp and broad domain walls

We discuss time-quantified Monte-Carlo simulations on classical spin chains with uniaxial anisotropy in relation to static calculations. Depending on the thickness of domain walls, controlled by the relative strength of the exchange and magnetic anisotropy energy, we found two distinct regimes in which both the static and dynamic behavior are different. For broad domain walls, the interplay between localized excitations and spin waves turns out to be crucial at finite temperature. As a consequence, a different protocol should be followed in the experimental characterization of slow-relaxing spin chains with broad domain walls with respect to the usual Ising limit.Comment: 18 pages, 13 figures, to be published in Phys. Rev.

Topoisomerase II beta mediates the resistance of glioblastoma stem cells to replication stress-inducing drugs

Background: Glioblastoma stem cells (GSC) have been extensively recognized as a plausible cause of glioblastoma resistance to therapy and recurrence resulting in high glioblastoma mortality. Abnormalities in the DNA repair pathways might be responsible for the inability of the currently used chemotherapeutics to eliminate the (GSC) subpopulation. Methods: In this work, we compared the expression of sixty DNA repair related genes between primary glioblastoma cell cultures and the glioblastoma enriched stem cell primary cultures. MTT test was used to analyze the effect of selected drugs and immunofluorescence to evaluate the load of DNA damage. Results: We found several differentially expressed genes and we identified topoisomerase II beta (Top2 beta) as the gene with highest up-regulation in GSC. Also among the tested cell lines the expression of Top2 beta was the highest in NCH421k cells, a well-characterized glioblastoma cell line with all the stemness characteristics. On the other hand, Top2 beta expression markedly decreased upon the induction of differentiation by all trans-retinoic acid. Depletion of Top2 beta increased the sensitivity of NCH421k cells to replication stress inducing drugs, such as cisplatin, methyl-methanesulfonate, hydrogen peroxide, and temozolomide. Consistently, we found an increased load of DNA damage and increased Chk1 activation upon Top2 beta depletion in NCH421k cells. Conclusion: We suggest that Top2 beta may represent a new target for gene therapy in glioblastoma. In addition, the other genes that we found to be up-regulated in GSC versus glioblastoma primary cells should be further investigated as glioblastoma theranostics

Membrane cholesterol modulates LOX-1 shedding in endothelial cells

The lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a scavenger receptor responsible for ox-LDL recognition, binding and internalization, which is up-regulated during atherogenesis. Its activation triggers endothelium dysfunction and induces inflammation. A soluble form of LOX-1 has been identified in the human blood and its presence considered a biomarker of cardiovascular diseases. We recently showed that cholesterol-lowering drugs inhibit ox-LDL binding and internalization, rescuing the ox-LDL induced apoptotic phenotype in primary endothelial cells. Here we have investigated the molecular bases of human LOX-1 shedding by metalloproteinases and the role of cell membrane cholesterol on the regulation of this event by modulating its level with MβCD and statins. We report that membrane cholesterol affects the release of different forms of LOX-1 in cells transiently and stably expressing human LOX-1 and in a human endothelial cell line (EA.hy926). In particular, our data show that i) cholesterol depletion triggers the release of LOX-1 in exosomes as a full-length transmembrane isoform and as a truncated ectodomain soluble fragment (sLOX-1); ii) endothelial cells secrete a soluble metalloproteinase which induces LOX-1 ectodomain shedding and iii) long term statins treatment enhances sLOX-1 proteolytic shedding

Glauber slow dynamics of the magnetization in a molecular Ising chain

The slow dynamics (10^-6 s - 10^4 s) of the magnetization in the paramagnetic phase, predicted by Glauber for 1d Ising ferromagnets, has been observed with ac susceptibility and SQUID magnetometry measurements in a molecular chain comprising alternating Co{2+} spins and organic radical spins strongly antiferromagnetically coupled. An Arrhenius behavior with activation energy Delta=152 K has been observed for ten decades of relaxation time and found to be consistent with the Glauber model. We have extended this model to take into account the ferrimagnetic nature of the chain as well as its helicoidal structure.Comment: 4 pages, 4 figures (low resolution), 16 references. Submitted to Physical Review Letter