CoCrMo alloys ions release behavior by TiNbN coating: an in vitro study.

The aim of the study was to show in vitro the greater inertness to the corrosion body fluid of TiNbN coating than the CoCrMo alloy substrate. The prosthetic component under study was a femoral component of total knee prosthesis in CoCrMo alloy coated in TiNbN with Physical Vapor Deposition technique immersed in static Hank's balanced salt solution (HBS) (pH = 6) for at least 34 months at a constant temperature of 37 °C. Another uncoated prosthetic component of CoCrMo alloy with the same type and size was left in static immersion in the same solution and for the same period of time. Scanning electron microscope (SEM) analysis was performed to investigate adhesion and proliferation at 24, 48, 72 h after seeding of 104 sub-confluents osteoblast-like cells (SaOS-2) cells on scaffold. The results of the study showed a reduction in the concentration of the metal ions released from the TiNbN-coated femoral component surface compared to the uncoated surface in the HBS solution. The overall reduction of the ions for the TiNbN-coated femoral component compared to the uncoated one was 80.1 ± 2%, 62.5% ± 8% and 48% ± 10% for Co, Cr, Mo, respectively (p < 0.01). SEM analysis confirmed the healthy state of the cells, the cellular adhesion and proliferation of SaOS-2 on the TiNbN-coated specimen. Although the results observed in vitro for the TiNbN coating are encouraging, clinical studies are certainly needed to be performed in order to understand how these positive findings can be translated in vivo and to determine the clinical benefit of TiNbN coating.

Respiratory metabolism and calorie restriction relieve persistent endoplasmic reticulum stress induced by calcium shortage in yeast.

Calcium homeostasis is crucial to eukaryotic cell survival. By acting as an enzyme cofactor and a second messenger in several signal transduction pathways, the calcium ion controls many essential biological processes. Inside the endoplasmic reticulum (ER) calcium concentration is carefully regulated to safeguard the correct folding and processing of secretory proteins. By using the model organism Saccharomyces cerevisiae we show that calcium shortage leads to a slowdown of cell growth and metabolism. Accumulation of unfolded proteins within the calcium-depleted lumen of the endoplasmic reticulum (ER stress) triggers the unfolded protein response (UPR) and generates a state of oxidative stress that decreases cell viability. These effects are severe during growth on rapidly fermentable carbon sources and can be mitigated by decreasing the protein synthesis rate or by inducing cellular respiration. Calcium homeostasis, protein biosynthesis and the unfolded protein response are tightly intertwined and the consequences of facing calcium starvation are determined by whether cellular energy production is balanced with demands for anabolic functions. Our findings confirm that the connections linking disturbance of ER calcium equilibrium to ER stress and UPR signaling are evolutionary conserved and highlight the crucial role of metabolism in modulating the effects induced by calcium shortage.

Proteomic analysis of a nutritional shift-up in Saccharomyces cerevisiae identifies Gvp36 as a BAR-containing protein involved in vesicular traffic and nutritional adaptation.

Yeast cells undergoing a nutritional shift-up from a poor to a rich carbon source take several hours to adapt to the novel, richer carbon source. The budding index is a physiologically relevant "global" parameter that reflects the complex links between cell growth and division that are both coordinately and deeply affected by nutritional conditions. We used changes in budding index as a guide to choose appropriate, relevant time points during an ethanol to glucose nutritional shift-up for preparation of samples for the analysis of proteome by two-dimensional electrophoresis/mass spectrometry. About 600 spots were detected. 90 spots, mostly comprising proteins involved in intermediary metabolism, protein synthesis, and response to stress, showed differential expression after glucose addition. Among modulated proteins we identified a protein of previously unknown function, Gvp36, showing a transitory increase corresponding to the drop of the fraction of budded cells. A gvp36Delta strain shares several phenotypes (including general growth defects, heat shock, and high salt sensitivity, defects in polarization of the actin cytoskeleton, in endocytosis and in vacuolar biogenesis, defects in entering stationary phase upon nutrient starvation) with secretory pathway mutants and with mutants in genes encoding the two previously known yeast BAR proteins (RSV161 and RSV167). We thus propose that Gvp36 represents a novel yeast BAR protein involved in vesicular traffic and in nutritional adaptation.

Messages in molecules: ligand/cation coding and self-recognition in a constitutionally dynamic system of heterometallic double helicates.

Double helicates are known to exhibit self-recognition characteristics determined by the coordination geometry of the metal involved as well as by the topicity of the ligands. Combining tridentate (terpyridine, T) or bidentate (bipyridine, B) subunits in a tritopic strand affords a set of ligands able to assemble by pairs to form double helicates, homo- or heterostranded, homo- or heterotopic, depending on the coordination properties of the metals involved. The four ligand strands, BBB, TTT, BBT, and TBT form constitutionally dynamic sets of double helicates with the metal ions Cu(I), Cu(II), and Zn(II); these helicates correspond to the correct coding of the BB, BT, and TT pairs for tetra-, penta-, and hexacoordinate Cu(I), Cu(II), and Zn(II) cations, respectively.