Hynowska A.,Departament Of Fi Sicauniversitat Auto`Noma Of Barcelonabellaterrae 08193 Spain |
Blanquer A.,Departament de Biologia Cellular |
Pellicer E.,Departament Of Fi Sicauniversitat Auto`Noma Of Barcelonabellaterrae 08193 Spain |
Fornell J.,Departament Of Fi Sicauniversitat Auto`Noma Of Barcelonabellaterrae 08193 Spain |
And 9 more authors.
Journal of Biomedical Materials Research - Part B Applied Biomaterials
The microstructure, mechanical behaviour, and biocompatibility (cell culture, morphology, and cell adhesion) of nanostructured Ti45Zr15Pd35- xSi5Nbx with x=0, 5 (at. %) alloys, synthesized by arc melting and subsequent Cu mould suction casting, in the form of rods with 3 mm in diameter, are investigated. Both Ti-Zr-Pd-Si-(Nb) materials show a multi-phase (composite-like) microstructure. The main phase is cubic β-Ti phase (Im3m) but hexagonal α-Ti (P63/mmc), cubic TiPd (Pm3m), cubic PdZr (Fm3m), and hexagonal (Ti, Zr)5Si3 (P63/mmc) phases are also present. Nanoindentation experiments show that the Ti45Zr15Pd30Si5Nb5 sample exhibits lower Young's modulus than Ti45Zr15Pd35Si5. Conversely, Ti45Zr15Pd35Si5 is mechanically harder. Actually, both alloys exhibit larger values of hardness when compared with commercial Ti-40Nb, (HTi-Zr-Pd-Si ≈ 14 GPa, HTi-Zr-Pd-Si-Nb ≈ 10 GPa and HTi-40Nb ≈ 2.7 GPa). Concerning the biological behaviour, preliminary results of cell viability performed on several Ti-Zr-Pd-Si-(Nb) discs indicate that the number of live cells is superior to 94% in both cases. The studied Ti-Zr-Pd-Si-(Nb) bulk metallic system is thus interesting for biomedical applications because of the outstanding mechanical properties (relatively low Young's modulus combined with large hardness), together with the excellent biocompatibility. © 2014 Wiley Periodicals, Inc. Source
Llopis A.,Departament de Biologia Cellular |
Salvador N.,Departament de Biologia Cellular |
Ercilla A.,Departament de Biologia Cellular |
Guaita-Esteruelas S.,Departament de Biologia Cellular |
And 7 more authors.
Accurate DNA replication is crucial for the maintenance of genome integrity. To this aim, cells have evolved complex surveillance mechanisms to prevent mitotic entry in the presence of partially replicated DNA. ATR and Chk1 are key elements in the signal transduction pathways of DNA replication checkpoint; however, other kinases also make significant contributions. We show here that the stress kinases p38 and JNK are activated when DNA replication is blocked, and that their activity allows S/M, but not G2/M, checkpoint maintenance when Chk1 is inhibited. Activation of both kinases by DNA replication inhibition is not mediated by the caffeine-sensitive kinases ATR or ATM. Phosphorylation of MKK3/6 and MKK4, p38 and JNK upstream kinases was also observed upon DNA replication inhibition. Using a genetic approach, we dissected the p38 pathway and showed that both p38 á and p38 â isoforms collaborate to inhibit mitotic entry. We further defined MKK3/6 and MK2/3 as the key upstream and downstream elements in the p38 signaling cascade after replication arrest. Accordingly, we found that the stress signaling pathways collaborate with Chk1 to keep cyclin B1/Cdk1 complexes inactive when DNA replication is inhibited, thereby preventing cell cycle progression when DNA replication is stalled. Our results show a complex response to replication stress, where multiple pathways are activated and fulfill overlapping roles to prevent mitotic entry with unreplicated DNA. © 2012 Landes Bioscience. Source