Peroxisome-localized hepatitis Bx protein increases the invasion property of hepatocellular carcinoma cells.

HBx acts as a multifunctional regulator that modulates various cellular responses, which can lead to development and progression of hepatocellular carcinoma (HCC). Here, we show that the HBx protein is also localized to peroxisomes, and this increases cellular reactive oxygen species (ROS) to levels that are higher than when HBx is localized to other organelles. The elevated ROS strongly activated nuclear factor (NF)-κB. In addition, the peroxisome-localized HBx increased the expressions of matrix metalloproteinases and decreased the expression of E-cadherin, which increased the invasive ability of HCC cells. Thus, a specific distribution of HBx to peroxisomes may contribute to HCC progression by increasing the invasive ability of HCC cells through elevation of the cellular ROS level.

Neural correlates of audio-visual object recognition: effects of implicit spatial congruency.

Multisensory integration assists us to identify objects by providing multiple cues with respect to object category and spatial location. We used a semantic audiovisual object matching task to determine the effect of spatial congruency on response behavior and fMRI brain activation. Fifteen subjects responded in a four-alternative response paradigm, which visual quadrant contained the object best matched to the sound presented. Realistic sounds based on head-related transfer functions were presented binaurally with the simulated sound source corresponding to one of the four quadrants. Following a random sequence, the location of the sound corresponded to the quadrant containing the semantically congruent target on half the trials, whereas on other trials the sound arose from an incongruent location. We examined the effects of spatial congruency on response latencies, hit-rates and fMRI responses. Preliminary behavioral results revealed a significant effect of spatial congruency on response latency or performance for stimuli with noise added. In the fMRI experiment, spatial congruency had a significant effect on the BOLD response. A cluster in the right middle and superior temporal gyrus was more activated when the auditory sound sources were spatially congruent with the semantically matching visual stimulus. In an exploratory post-hoc analysis, in which we correlated the BOLD signal with the subjects' ability to locate the sound sources, we found a significant cluster in the left inferior frontal cortex, where the BOLD response increased with sound-source localization performance. Thus spatial congruency appears to enhance the semantic integration of audiovisual object information in these brain regions.

Psychoacoustic evaluation of multichannel reproduced sounds using binaural synthesis and spherical beamforming.

The binaural auralization of a 3D sound field using spherical-harmonics beamforming (SHB) techniques was investigated and compared with the traditional method using a head-and-torso simulator (HATS). The new procedure was verified by comparing simulated room impulse responses with measured ones binaurally. The objective comparisons show that there is good agreement in the frequency range between 0.1 and 6.4 kHz. A listening experiment was performed to validate the SHB method subjectively and to compare it to the HATS method. Two musical excerpts, pop and classical, were used. Subjective responses were collected in two head rotation conditions (fixed and rotating) and six spatial reproduction modes, including phantom mono, stereo, and surround sound. The results show that subjective scales of width, spaciousness, and preference based on the SHB method were similar to those obtained for the HATS method, although the width and spaciousness of the stimuli processed by the SHB method were judged slightly higher than the ones using the HATS method in general. Thus, binaural synthesis using SHB may be a useful tool to reproduce a 3D sound field binaurally, while saving considerably on measurement time because head rotation can be simulated based on a single recording.

Cytokine-like 1 knock-out mice (Cytl1-/-) show normal cartilage and bone development but exhibit augmented osteoarthritic cartilage destruction.

We have shown that cytokine-like 1 (Cytl1) is a novel autocrine regulatory factor that regulates chondrogenesis of mouse mesenchymal cells (Kim, J. S., Ryoo, Z. Y., and Chun, J. S. (2007) J. Biol. Chem. 282, 29359-29367). In this previous work, we found that Cytl1 expression was very low in mesenchymal cells, increased dramatically during chondrogenesis, and decreased during hypertrophic maturation, both in vivo and in vitro. Moreover, exogenous addition or ectopic expression of Cytl1 caused chondrogenic differentiation of mouse limb bud mesenchymal cells. In the current study, we generated a Cytl1 knock-out (Cytl1(-/-)) mouse to investigate the in vivo role of Cytl1. Deletion of the Cytl1 gene did not affect chondrogenesis or cartilage development. Cytl1(-/-) mice also showed normal endochondral ossification and long bone development. Additionally, ultrastructural features of articular cartilage, such as matrix organization and chondrocyte morphology, were similar in wild-type and Cytl1(-/-) mice. However, Cytl1(-/-) mice were more sensitive to osteoarthritic (OA) cartilage destruction. Compared with wild-type littermates, Cytl1(-/-) mice showed more severe OA cartilage destruction upon destabilization of the medial meniscus of mouse knee joints. In addition, expression levels of Cytl1 were markedly decreased in OA cartilage of humans and experimental mice. Taken together, our results suggest that, rather than regulating cartilage and bone development, Cytl1 is required for the maintenance of cartilage homeostasis, and loss of Cytl1 function is associated with experimental OA cartilage destruction in mice.

The influence of company identity on the perception of vehicle sounds.

In order to determine how the interior of a car should sound, automotive manufacturers often rely on obtaining data from individual evaluations of vehicle sounds. Company identity could play a role in these appraisals, particularly when individuals are comparing cars from opposite ends of the performance spectrum. This research addressed the question: does company identity influence the evaluation of automotive sounds belonging to cars of a similar performance level and from the same market segment? Participants listened to car sounds from two competing manufacturers, together with control sounds. Before listening to each sound, participants were presented with the correct company identity for that sound, the incorrect identity or were given no information about the identity of the sound. The results showed that company identity did not influence appraisals of high performance cars belonging to different manufacturers. These results have positive implications for methodologies employed to capture the perceptions of individuals. STATEMENT OF RELEVANCE: A challenge in automotive design is to set appropriate targets for vehicle sounds, relying on understanding subjective reactions of individuals to such sounds. This paper assesses the role of company identity in influencing these subjective reactions and will guide sound evaluation studies, in which the manufacturer is often apparent.

Using beamforming and binaural synthesis for the psychoacoustical evaluation of target sources in noise.

The potential of spherical-harmonics beamforming (SHB) techniques for the auralization of target sound sources in a background noise was investigated and contrasted with traditional head-related transfer function (HRTF)-based binaural synthesis. A scaling of SHB was theoretically derived to estimate the free-field pressure at the center of a spherical microphone array and verified by comparing simulated frequency response functions with directly measured ones. The results show that there is good agreement in the frequency range of interest. A listening experiment was conducted to evaluate the auralization method subjectively. A set of ten environmental and product sounds were processed for headphone presentation in three different ways: (1) binaural synthesis using dummy head measurements, (2) the same with background noise, and (3) SHB of the noisy condition in combination with binaural synthesis. Two levels of background noise (62, 72 dB SPL) were used and two independent groups of subjects (N=14) evaluated either the loudness or annoyance of the processed sounds. The results indicate that SHB almost entirely restored the loudness (or annoyance) of the target sounds to unmasked levels, even when presented with background noise, and thus may be a useful tool to psychoacoustically analyze composite sources.

Regulation of type II collagen expression by cyclin-dependent kinase 6, cyclin D1, and p21 in articular chondrocytes.

This study examined whether cell cycle regulatory proteins, such as cyclin-dependent kinases (CDKs), cyclins, and CDK inhibitors, regulate type II collagen expression and mediate interlukin-1 (IL-1beta)-induced suppression of type II collagen expression in articular chondrocytes. IL-1beta inhibited type II collagen expression, but activated CDK6. Ectopic expression of CDK2 did not alter type II collagen expression. However, overexpression of CDK6 inhibited type II collagen expression, whereas inhibition of CDK6 activity blocked IL-1beta-induced suppression of type II collagen expression. IL-1beta upregulated the expression of cyclin D1, which is known to activate CDK6. In turn, overexpression of cyclin D1 suppressed type II collagen expression. In contrast to cyclin D1, IL-1beta triggered down-regulation of the CDK inhibitor, p21. Overexpression of p21 blocked IL-1beta- or CDK6-induced suppression of type II collagen expression. Our results collectively indicate that CDK6/cyclin D1/p21 complex regulates type II collagen expression in articular chondrocytes.

Identification and characterization of arginase II as a chondrocyte phenotype-specific gene.

We have previously shown that activation of extracellular signal-regulated protein kinase-1 and -2 (ERK1/2) causes chondrocyte dedifferentiation, which contributes to the destruction of arthritic cartilage. In the present study, we identified genes involved in the ERK1/2 regulation of chondrocyte dedifferentiation. Several genes were identified by subtractive hybridization, and, of these, arginase II was selected for further functional characterization. Similar to the pattern of type II collagen expression, which is a hallmark of chondrocyte differentiation, arginase II expression was increased during chondrogenesis of mesenchymal cells. The high expression level of arginase II was decreased during dedifferentiation of chondrocytes, whereas its expression was restored during redifferentiation of the dedifferentiated chondrocytes. Inhibition of ERK1/2 signaling in chondrocytes enhanced type II collagen expression with a concomitant increase in expression and activity of arginase II. However, ectopic expression of arginase II or inhibition of its activity did not affect chondrocyte differentiation. The results collectively indicate that expression of arginase II is specific to the chondrocyte phenotype, although the expression of arginase II alone is not sufficient for articular chondrocytes to maintain a differentiated phenotype.

p38 kinase-dependent and -independent Inhibition of protein kinase C zeta and -alpha regulates nitric oxide-induced apoptosis and dedifferentiation of articular chondrocytes.

In articular chondrocytes, nitric oxide (NO) production triggers dedifferentiation and apoptotic cell death that is regulated by the converse functions of two mitogen-activated protein kinase subtypes, extracellular signal-regulated kinase (ERK) and p38 kinase. Since protein kinase C (PKC) transduces signals that influence differentiation, survival, and apoptosis of various cell types, we investigated the roles and underlying molecular mechanisms of action of PKC isoforms in NO-induced dedifferentiation and apoptosis of articular chondrocytes. We report here that among the expressed isoforms, activities of PKCalpha and -zeta were reduced during NO-induced dedifferentiation and apoptosis. Inhibition of PKCalpha activity was independent of NO-induced activation of ERK or p38 kinase and occurred due to blockage of expression. On the other hand, PKCzeta activity was inhibited as a result of NO-induced p38 kinase activation and was observed prior to proteolytic cleavage by a caspase-mediated process to generate enzymatically inactive fragments. Inhibition of PKCalpha or -zeta activities potentiated NO-induced apoptosis, whereas ectopic expression of these isoforms significantly reduced the number of apoptotic cells and blocked dedifferentiation. Ectopic expression of PKCalpha or -zeta did not affect p38 kinase or ERK but inhibited the p53 accumulation and caspase-3 activation that are required for NO-induced apoptosis of chondrocytes. Therefore, our results collectively indicate that p38 kinase-independent and -dependent inhibition of PKCalpha and -zeta, respectively, regulates NO-induced apoptosis and dedifferentiation of articular chondrocytes.