Thapsigargin modulates osteoclastogenesis through the regulation of RANKL-induced signaling pathways and reactive oxygen species production

Introduction: Apoptosis and differentiation are among the consequences of changes in intracellular Ca2+ levels. In this study, we investigated the effects of the endoplasmic reticular Ca2+-ATPase inhibitor, thapsigargin (TG), on osteoclast apoptosis and differentiation. Materials and Methods: Both RAW264.7 cells and primary spleen cells were used to examine the effect of TG on RANKL-induced osteoclastogenesis. To determine the action of TG on signaling pathways, we used reporter gene assays for NF-kappa B and activator protein-1 (AP-1) activity, Western blotting for phosphoextracellular signal-related kinase (ERK), and fluorescent probes to measure changes in levels of intracellular calcium and reactive oxygen species (ROS). To assess rates of apoptosis, we measured changes in annexin staining, caspase-3 activity, and chromatin and F-actin microfilament structure. Results: At concentrations that caused a rapid rise in intracellular Ca2+, TG increased caspase-3 activity and promoted apoptosis in osteoclast-like cells (OLCs). Low concentrations of TG, which were insufficient to measurably alter intracellular Ca2+, unexpectedly suppressed caspase-3 activity and enhanced RANKL-induced osteoclastogenesis. At these lower concentrations, TG potentiated ROS production and RANKL-induced NF-kappa B activity, but suppressed RANKL-induced AP-1 activity and had little effect on ERK phosphorylation. Conclusion: Our novel findings of a biphasic effect of TG are incompletely explained by our current understanding of TG action, but raise the possibility that low intensity or local changes in subcellular Ca2+ levels may regulate intracellular differentiation signaling. The extent of cross-talk between Ca2+ and RANKL-mediated intracellular signaling pathways might be important in determining whether cells undergo apoptosis or differentiate into OLCs.

Through the lenses of organizational culture: A comparison of state-owned enterprises and joint ventures in China

This study compared state-owned enterprises (SOEs) and joint ventures (JVs) in light of organizational culture practices. Data were obtained via a survey participated by 781 respondents from five enterprises. Factoring identified four cultural dimensions: Participation, Teamwork, Supervision, and Meetings. All four dimensions, except Participation, were rated significantly higher by respondents from SOEs as compared to the ratings in JVs. Based on the findings, this study concluded that culture practices valued in one type of enterprise might be liability in another. The implication for management is to gear culture practices to the characteristics of the organization to make it successful.

Facilitating soil-and plant-water research through the use of TDR

The development of TDR for measurement of soil water content and electrical conductivity has resulted in a large shift in measurement methods for a breadth of soil and hydrological characterization efforts. TDR has also opened new possibilities for soil and plant research. Five examples show how TDR has enhanced our ability to conduct our soil- and plant-water research. (i) Oxygen is necessary for healthy root growth and plant development but quantitative evaluation of the factors controlling oxygen supply in soil depends on knowledge of the soil water content by TDR. With water content information we have modeled successfully some impact of tillage methods on oxygen supply to roots and their growth response. (ii) For field assessment of soil mechanical properties influencing crop growth, water content capability was added to two portable soil strength measuring devices; (a) A TDT (Time Domain Transmittivity)-equipped soil cone penetrometer was used to evaluate seasonal soil strengthwater content relationships. In conventional tillage systems the relationships are dynamic and achieve the more stable no-tillage relationships only relatively late in each growing season; (b) A small TDR transmission line was added to a modified sheargraph that allowed shear strength and water content to be measured simultaneously on the same sample. In addition, the conventional graphing procedure for data acquisition was converted to datalogging using strain gauges. Data acquisition rate was improved by more than a factor of three with improved data quality. (iii) How do drought tolerant plants maintain leaf water content? Non-destructive measurement of TDR water content using a flat serpentine triple wire transmission line replaces more lengthy procedures of measuring relative water content. Two challenges remain: drought-stressed leaves alter salt content, changing electrical conductivity, and drought induced changes in leaf morphology affect TDR measurements. (iv) Remote radar signals are reflected from within the first 2 cm of soil. Appropriate calibration of radar imaging for soil water content can be achieved by a parallel pair of blades separated by 8 cm, reaching 1.7 cm into soil and forming a 20 cm TDR transmission line. The correlation between apparent relative permittivity from TDR and synthetic aperture radar (SAR) backscatter coefficient was 0.57 from an airborne flyover. These five examples highlight the diversity in the application of TDR in soil and plant research.

Enhancing performance through the introduction of customer orientation into the building components industry

Purpose: This paper aims to describe an investigation into how company performance can be improved by integrating internal and external customers and technology. The approach was developed, implemented and evaluated in the operations of the building components industry. The research was carried out in the precast concrete division of a Singapore company. Design/methodology/ approach: For the purpose of undertaking the investigation an exploratory case study approach was used. This was divided into conceptual and action research stages. The action research was also used to implement the changes in the company. Questionnaire surveys were carried out among company employees and external customers to assess the effect of these changes. Results of the investigation were derived using content and statistical analysis. Triangulation between three sources was used for validating the data. Findings: The exploratory case study strategy resulted in rich research data, which provided evidence of the changes taking place and integration happening, leading to improved performance. The action research approach proved a powerful tool where the uncertainty of outcomes makes it near impossible to make accurate forecasts. Another output of the research was the development of an "integrated customer orientation" (ICO) model. Research limitations/implications: The research in this paper used a single site action research investigation so should be interpreted within the specific company and industry context. There are implications for theory and practice in a number of areas of production and marketing as well as contributions to understanding about productivity improvement and organisational development. The investigation also fulfils the dual objectives of action research by contributing to both knowledge and practice. Originality/value: The paper describes a unique approach towards improving productivity, quality and service through the use of action research to implement changes, as well as providing the research evidence to evaluate both the process of implementation and results achieved. © Emerald Group Publishing Limited.