Nod1 acts as an intracellular receptor to stimulate chemokine production and neutrophil recruitment in vivo

Nod1 is a member of family of intracellular proteins that mediate host recognition of bacterial peptidoglycan. To characterize immune responses mediated by Nod1, synthetic ligand compounds possessing enhanced ability to stimulate Nod1 were developed to study the function of Nod1. Stimulation of epithelial cells with Nod1 stimulatory molecules induced chemokines and other proinflammatory molecules that are important for innate immune responses and recruitment of acute inflammatory cells. Administration of Nod1 ligands into mice induced chemokines and recruitment of acute inflammatory cells, an activity that was abolished in Nod1-null mice. Microarray analysis revealed that Nod1 stimulation induces a restricted number of genes in intestinal epithelial cells compared with that induced by tumor necrosis factor (TNF) α. Nod1 stimulation did not induce TNFα, interleukin 12, and interferon γ, suggesting that the primary role of Nod1 is to induce the recruitment of immune cells. These results indicate that Nod1 functions as a pathogen recognition molecule to induce expression of molecules involved in the early stages of the innate immune response

PPARγ contributes to PKM2 and HK2 expression in fatty liver

Rapidly proliferating cells promote glycolysis in aerobic conditions, to increase growth rate. Expression of specific glycolytic enzymes, namely pyruvate kinase M2 and hexokinase 2, concurs to this metabolic adaptation, as their kinetics and intracellular localization favour biosynthetic processes required for cell proliferation. Intracellular factors regulating their selective expression remain largely unknown. Here we show that the peroxisome proliferator-activated receptor gamma transcription factor and nuclear hormone receptor contributes to selective pyruvate kinase M2 and hexokinase 2 gene expression in PTEN-null fatty liver. Peroxisome proliferator-activated receptor gamma expression, liver steatosis, shift to aerobic glycolysis and tumorigenesis are under the control of the Akt2 kinase in PTEN-null mouse livers. Peroxisome proliferator-activated receptor gamma binds to hexokinase 2 and pyruvate kinase M promoters to activate transcription. In vivo rescue of peroxisome proliferator-activated receptor gamma activity causes liver steatosis, hypertrophy and hyperplasia. Our data suggest that therapies with the insulin-sensitizing agents and peroxisome proliferator-activated receptor gamma agonists, thiazolidinediones, may have opposite outcomes depending on the nutritional or genetic origins of liver steatosis

Regulation of the MDM2-P53 pathway and tumor growth by PICT1 via nucleolar RPL11

PICT1 (also known as GLTSCR2) is considered a tumor suppressor because it stabilizes phosphatase and tensin homolog (PTEN), but individuals with oligodendrogliomas lacking chromosome 19q13, where PICT1 is located, have better prognoses than other oligodendroglioma patients. To clarify the function of PICT1, we generated Pict1-deficient mice and embryonic stem (ES) cells. Pict1 is a nucleolar protein essential for embryogenesis and ES cell survival. Even without DNA damage, Pict1 loss led to p53-dependent arrest of cell cycle phase G1 and apoptosis. Pict1-deficient cells accumulated p53, owing to impaired Mdm2 function. Pict1 binds Rpl11, and Rpl11 is released from nucleoli in the absence of Pict1. In Pict1-deficient cells, increased binding of Rpl11 to Mdm2 blocks Mdm2-mediated ubiquitination of p53. In human cancer, individuals whose tumors express less PICT1 have better prognoses. When PICT1 is depleted in tumor cells with intact P53 signaling, the cells grow more slowly and accumulate P53. Thus, PICT1 is a potent regulator of the MDM2-P53 pathway and promotes tumor progression by retaining RPL11 in the nucleolu

Knowledge Integration in a Product Development Organization Accompanied by M&A : A Case Study of a Precision Device Manufacturer

This case study of a precision device manufacturer discusses knowledge integration in a product development organization after M&A. The goal is to contribute to establishment of a methodology that helps to accomplish the purpose of M&A. The special feature is to analyze establishment of a new product development organization, and its entry into a new market from the standpoint of knowledge management. This study proposes the ”ARC Model” to explain knowledge integration in product development organizations after M&A. Knowledge integration is conducted in three phases, i.e., ”Assessment”, “Reorganization” and ”Cooperation”. In the first phase, knowledge of the acquiring company and the acquired company is assessed. In the second phase, product development organizations are reorganized based on assessment in the first phase. Strategic transfer and far transfer of existing knowledge are conducted. In the third phase, knowledge is created in the process of product development in the new organization. Near transfer and serial transfer of the newly created knowledge are conducted. This study indicates that one of the adverse factors against knowledge integration in product development organizations is difference of corporate cultures and another is persistence of knowledge not necessary for the new market

Importance of Intrinsic Motivation for Knowledge Sharing within an R&D Organization

The purpose of this study is to investigate the role of intrinsic motivation of R&D researchers for knowledge sharing within an R&D organization using statistical analysis. We mainly focused on and analyzed individuals who participate in basic or applied research, because study of knowledge sharing should begin with the individual. A questionnaire survey of 398 R&D researchers was conducted in the R&D laboratory of a Japanese Electronics Manufacturing Company. The analysis showed that intrinsic motivation greatly enhanced knowledge contribution as a part of functions for knowledge sharing, more than extrinsic satisfaction of the R&D researchers. From these findings, we inferred an important role of intrinsic motivation in sharing knowledge within an R&D organization.The original publication is available at JAIST Press http://www.jaist.ac.jp/library/jaist-press/index.htmlProceedings of KSS'2007 : The Eighth International Symposium on Knowledge and Systems Sciences : November 5-7, 2007, [Ishikawa High-Tech Conference Center, Nomi, Ishikawa, JAPAN]Organized by: Japan Advanced Institute of Science and Technolog

Adverse Factors of Knowledge Integration in a Product Development Organization after M&A : A Case Study of a Precision Device Manufacturer

This study discusses knowledge integration in a product development organization after M&A. The goal is to contribute to establishment of methodology that helps to accomplish the purpose of M&A. This study analyzes establishment of a new product development organization and its entry into a new market. This study indicates that knowledge integration is conducted in three phases: 1) Knowledge of the acquiring company and the acquired company is assessed. 2) Product development organization is reorganized based on the assessment. 3) Knowledge is created in the process of product development in the new organization. This study indicates that one of the adverse factors against knowledge integration in product development organizations is difference of corporate cultures between the acquiring company and the acquired company. This problem will be resolved in mid-term and long-term, since new corporate culture will mature in the product development organization. If the acquiring company persists on its existing knowledge, it is difficult to develop new products suitable for the new market. Thus another adverse factor against knowledge integration is persistence in the knowledge not necessary for the new market. In order to prevent this, abandonment of such knowledge is conducted during reorganization of the product development organization

Managing Individual Autonomy to Increase Intrinsic Motivation within a New Product Development Organization in Japan

Intrinsic motivation is one of the most important individual factors to enhance the team’s creativity in New Product Development (NPD). Many social psychological studies have pointed out that intrinsic motivation is heightened through enhancing individual autonomy. However, managing individual autonomy in a work situation has not yet been adequately addressed nor discussed in detail. In this research, we investigated how to improve individual autonomy focusing on NPD personnel, such as those in design, development, manufacturing and quality-control, as well as in marketing departments. From questionnaire data collected from 242 NPD members within a Japanese industrial machine manufacturing company, we quantitatively analyzed the effects of various ways of giving autonomy to individuals. The results of this statistical analysis showed that individual autonomy was enhanced only when individuals could decide what they should accomplish in their work and how they should do their work. We revealed the importance of autonomy in motivating working professionals intrinsically, and how autonomy could be effectively given to individuals in a work situation. Also, we found that autonomy given to individuals had no direct effect on intrinsic motivation.Portland International Conference on Management of Engineering & Technology (PICMET 2008), 27-31 July, Cape Town, South Afric