ITPKC functional polymorphism associated with Kawasaki disease susceptibility and formation of coronary artery aneurysms

Kawasaki disease is a pediatric systemic vasculitis of unknown etiology for which a genetic influence is suspected. We identified a functional SNP (itpkc_3) in the inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) gene on chromosome 19q13.2 that is significantly associated with Kawasaki disease susceptibility and also with an increased risk of coronary artery lesions in both Japanese and US children. Transfection experiments showed that the C allele of itpkc_3 reduces splicing efficiency of the ITPKC mRNA. ITPKC acts as a negative regulator of T-cell activation through the Ca2+/NFAT signaling pathway, and the C allele may contribute to immune hyper-reactivity in Kawasaki disease. This finding provides new insights into the mechanisms of immune activation in Kawasaki disease and emphasizes the importance of activated T cells in the pathogenesis of this vasculitis.     

HOW ARE PRODUCT-SERVICE COMBINED OFFERS PROVIDED IN GERMANY AND ITALY？ ANALYSIS WITH COMPANY SIZES AND COUNTRIES

A new business concept that offers products and services in a different way of traditional product-sales businesses is getting more attention especially in manufacturing industries. This paper investigates how this new business by means of integration of products and services is achieved in Germany and Italy. In addition, it analyzes the differences according to the company sizes. The results include that this type of business is in many cases motivated by their focus on customers and often consists of physical products and their maintenance. The Italian companies, as opposed to the German ones, often design their physical products specifically for this type of offers. From the analysis based on the size difference, small companies are found to achieve specific design for this type of offers while owning physical products. There do not seem to be any established methods or tools developed to support the development of such offers and within such methods/tools there would be room for more adaptation in form of physical product design.     

TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity

Retinoic-acid-inducible gene-I (RIG-I; also called DDX58) is a cytosolic viral RNA receptor that interacts with MAVS (also called VISA, IPS-1 or Cardif) to induce type I interferon-mediated host protective innate immunity against viral infection. Furthermore, members of the tripartite motif (TRIM) protein family, which contain a cluster of a RING-finger domain, a B box/coiled-coil domain and a SPRY domain, are involved in various cellular processes, including cell proliferation and antiviral activity. Here we report that the amino-terminal caspase recruitment domains (CARDs) of RIG-I undergo robust ubiquitination induced by TRIM25 in mammalian cells. The carboxy-terminal SPRY domain of TRIM25 interacts with the N-terminal CARDs of RIG-I; this interaction effectively delivers the Lys 63-linked ubiquitin moiety to the N-terminal CARDs of RIG-I, resulting in a marked increase in RIG-I downstream signalling activity. The Lys 172 residue of RIG-I is critical for efficient TRIM25-mediated ubiquitination and for MAVS binding, as well as the ability of RIG-I to induce antiviral signal transduction. Furthermore, gene targeting demonstrates that TRIM25 is essential not only for RIG-I ubiquitination but also for RIG-I-mediated interferon- production and antiviral activity in response to RNA virus infection. Thus, we demonstrate that TRIM25 E3 ubiquitin ligase induces the Lys 63-linked ubiquitination of RIG-I, which is crucial for the cytosolic RIG-I signalling pathway to elicit host antiviral innate immunity.     

Superconductors: unusual oxygen isotope effects in cuprates?

The possibility that a pairing boson might act as the 'glue' to bind electrons into a Cooper pair in superconductors with a high critical temperature (T(c)) is being actively pursued in condensed-matter physics. Gweon et al. claim that there is a large and unusual oxygen-isotope effect on the electronic structure, indicating that phonons have a special importance in high-temperature superconductors. However, we are unable to detect this unusual oxygen-isotope effect in new data collected under almost identical material and experimental conditions. Our findings point towards a more conventional influence of phonons in these materials.     

Uncovering benefits and risks of integrated product service offerings — Using a case of technology encapsulation

The objective of this article is to uncover benefits and risks of Integrated Product Service Offering （IPSO） in a systematic manner. To do so, it adopts an explorative longitudinal in-depth case study （development of an IPSO based on a new technology） and adds insights to the existing literature. The article first proposes a theoretical and generic framework termed the PCP （Provider - Customer - Product） triangle with associated information flow and uncertainty. Second, various types of benefits and risks are presented based on the framework. Among others, the benefit of keeping IPR （Intellectual Property Rights） with the provider and the risk of regulation change are new findings from the case study. In addition, the case study reveals that IPSO is regarded as a positive contributor to innovation. Applying the framework and classification of benefits and risks as norms to other cases has yet to be done for verification. However, the framework contributes scientifically to a better understanding of the benefits and risks of IPSO. In addition, this framework is advantageous with its easiness to understand, which contributes practically to the dissemination of IPS0 insight to industry.     

Efp targets 14-3-3 sigma for proteolysis and promotes breast tumour growth

Oestrogen exerts its influence on target organs through activating oestrogen receptors (ERs) and regulating downstream genes by means of their oestrogen-responsive elements. Efp, a target gene product of ER alpha, is a member of the RING-finger B-box coiled-coil (RBCC) motif family. Efp is predominantly expressed in various female organs as well as in breast cancers, and is thought to be essential for oestrogen-dependent cell proliferation and organ development Efp-disrupted mice display underdeveloped uteri and reduced oestrogen responsiveness. Here we show that Efp is a RING-finger-dependent ubiquitin ligase (E3) that targets proteolysis of 14-3-3 sigma, a negative cell cycle regulator that causes G2 arrest. We demonstrate that tumour growth of breast cancer MCF7 cells implanted in female athymic mice is reduced by treatment with antisense Efp oligonucleotide. Efp-overexpressing MCF7 cells in ovariectomized athymic mice generate tumours in the absence of oestrogen. Loss of Efp function in mouse embryonic fibroblasts results in an accumulation of 14-3-3 sigma, which is responsible for reduced cell growth. These data provide an insight into the cell-cycle machinery and tumorigenesis of breast cancer by identifying 14-3-3 sigma as a target for proteolysis by Efp, leading to cell proliferation.