Constitutive and functional expression of YB-1 in microglial cells.

Y-box-binding protein (YB-1) is a member of the cold-shock protein family and participates in a wide variety of DNA/RNA-dependent cellular processes including DNA repair, transcription, mRNA splicing, packaging, and translation. At the cellular level, YB-1 is involved in cell proliferation and differentiation, stress responses, and malignant cell transformation. A general role for YB-1 during inflammation has also been well described; however, there are minimal data concerning YB-1 expression in microglia, which are the immune cells of the brain. Therefore, we studied the expression of YB-1 in a clinically relevant global ischemia model for neurological injury following cardiac arrest. This model is characterized by massive neurodegeneration of the hippocampal CA1 region and the subsequent long-lasting activation of microglia. In addition, we studied YB-1 expression in BV-2 cells, which are an accepted microglia culture model. BV-2 cells were stressed by oxygen/glucose deprivation (OGD), OGD-relevant mediators, lipopolysaccharide (LPS), and phagocytosis-inducing cell debris and nanoparticles. Using quantitative polymerase chain reaction (PCR), we show constitutive expression of YB-1 transcripts in unstressed BV-2 cells. The functional upregulation of the YB-1 protein was demonstrated in microglia in vivo and in BV-2 cells in vitro. All stressors except for LPS were potent enhancers of the level of YB-1 protein, which appears to be regulated primarily by proteasomal degradation and, to a lesser extent, by the activation (phosphorylation) of the translation initiation factor eIF4E. The proteasome of BV-2 cells is impaired by OGD, which results in decreased protein degradation and therefore increased levels of YB-1 protein. LPS induces proteasome activity, which enables the level of YB-1 protein to remain at control levels despite enhanced protein ubiquitination. The proteasome inhibitor MG-132 was able to increase YB-1 protein levels in control and LPS-treated cultures. YB-1 upregulation was not accompanied by its translocation from the cytoplasm to the nucleus. YB-1 induction appeared to be related to microglial proliferation because it was partially co-regulated with Ki67. In addition, YB-1 protein levels correlated with microglia phagocytic activity because its upregulation could also be induced by inert NPs.

Improved mechanical long-term reliability of hip resurfacing prostheses by using silicon nitride.

Although ceramic prostheses have been successfully used in conventional total hip arthroplasty (THA) for many decades, ceramic materials have not yet been applied for hip resurfacing (HR) surgeries. The objective of this study is to investigate the mechanical reliability of silicon nitride as a new ceramic material in HR prostheses. A finite element analysis (FEA) was performed to study the effects of two different designs of prostheses on the stress distribution in the femur-neck area. A metallic (cobalt-chromium-alloy) Birmingham hip resurfacing (BHR) prosthesis and our newly designed ceramic (silicon nitride) HR prosthesis were hereby compared. The stresses induced by physiologically loading the femur bone with an implant were calculated and compared with the corresponding stresses for the healthy, intact femur bone. Here, we found stress distributions in the femur bone with the implanted silicon nitride HR prosthesis which were similar to those of healthy, intact femur bone. The lifetime predictions showed that silicon nitride is indeed mechanically reliable and, thus, is ideal for HR prostheses. Moreover, we conclude that the FEA and corresponded post-processing can help us to evaluate a new ceramic material and a specific new implant design with respect to the mechanical reliability before clinical application.

Further studies of phonation threshold pressure in a physical model of the vocal fold mucosa.

This paper reports results of further experimentation on a previously developed physical model of the vocal-fold mucosa [Titze et al., J. Acoust. Soc. Am. 97, 3080-3084 (1995)]. The effects of vocal-fold thickness, epithelial membrane thickness, and prephonatory glottal geometry on phonation threshold pressure were studied. Phonation threshold pressures in the range of 0.13 to 0.34 kPa were observed for an 11-mm-thick vocal fold with a 70-micron-thick "epithelial" membrane for different "mucosal" fluid viscosities. Higher threshold pressure was always obtained for thinner vocal folds and thicker membranes. In another set of experiments, lowest offset threshold pressure was obtained for a rectangular or a near-rectangular prephonatory glottis (with a glottal convergence angle within about +/- 3 degrees). It ranged from 0.07 to 0.23 kPa for different glottal half-widths between 2.0 and 6.0 mm. The threshold for more convergent or divergent glottal geometries was consistently higher. This finding only partially agrees with previous analytical work which predicts a lowest threshold for a divergent glottis. The discrepancy between theory and data is likely to be associated with flow separation from a divergent glottis.

Phonation threshold pressure in a physical model of the vocal fold mucosa.

The vocal fold mucosa, which consists of the epithelium and the superficial layer of the lamina propria, has been modeled by a fluid encapsulated in a silicone membrane. The artificial mucosa was attached to a rigid (metal) vocal fold body and introduced into an airflow channel, creating a rectangular glottis. Flow-induced oscillation of the mucosa was achieved at various subglottal pressures and glottal diameters. Phonation threshold pressure, the parameter of interest, was lowest (on the order of 0.4 kPa) for glottal diameters between 0.0 and 0.1 mm and for fluids with the lowest viscosity. There was a consistent hysteresis effect; that is, phonation threshold pressure was always lower for oscillation offset than onset.