Activated macrophages promote Wnt signaling through TNF-α in gastric tumor cells

Division of Genetic

A Practical and Scalable Decoder for Topological Quantum Error Correction with Digital Annealer

Quantum error correction is one of the most important milestones for realization of large-scale quantum computation. To achieve this, it is essential not only to integrate a large number of qubits with high fidelity, but also to build a scalable classical system that can perform error correction. Here, we propose an efficient and scalable decoder for quantum error correction using Fujitsu Digital Annealer (DA). Specifically, the error correction problem of stabilizer codes is mapped into an Ising-type optimization problem, so-called quadratic unconstrained binary optimization (QUBO) problem, which is solved by DA. In particular, we implement the proposed DA decoder for the surface code and perform detailed numerical experiments for various code distances to see its performance and scalability. We observe that computational scaling for the DA decoder has a lower order of polynomial than the decoding methods using simulated annealing (SA) and minimum-weight perfect matching (MWPM) algorithm under all tested conditions. Furthermore, the threshold behavior of the logical error probability for the DA decoder is analyzed and the resultant threshold value is about 9.7% which is very close to that obtained by the MWPM decoder. This result clearly shows the high potential of the DA decoder for quantum error correction.Comment: 10 pages, 11 figure

Prostaglandin E2, Wnt, and BMP in gastric tumor mouse models

金沢大学がん研究所がん幹細胞研究センターThe development of gastric cancer is closely associated with Helicobacter pylori (H. pylori) infection. The expression of cylooxigenase-2 (COX-2), a rate-limiting enzyme for prostaglandin biosynthesis, is induced in H. pylori-associated chronic gastritis, which thus results in the induction of proinflammatory prostaglandin, PGE2. The COX-2/PGE2 pathway plays a key role in gastric tumorigenesis. On the other hand, several oncogenic pathways have been shown to trigger gastric tumorigenesis. The activation of Wnt/β;-catenin signaling is found in 30-50% of gastric cancers, thus suggesting that Wnt signaling plays a causal role in gastric cancer development. Mutations in the bone morphogenetic protein (BMP) signaling pathway are responsible for the subset of juvenile polyposis syndrome (JPS) that develops hamartomas in the gastrointestinal tract. BMP suppression appears to contribute to gastric cancer development because gastric cancer risk is increased in JPS. Wnt signaling is important for the maintenance of gastrointestinal stem cells, while BMP promotes epithelial cell differentiation. Accordingly, it is possible that both Wnt activation and BMP suppression can cause gastric tumorigenesis through enhancement of the undifferentiated status of epithelial cells. Recent mouse model studies have indicated that induction of the PGE2 pathway is required for the development of both gastric adenocarcinoma and hamartoma in the Wnt-activated and BMP-suppressed gastric mucosa, respectively. This article reviews the involvement of the PGE2, Wnt, and BMP pathways in the development of gastric cancer, and gastric phenotypes that are found in transgenic mouse models of PGE2 induction, Wnt activation, BMP suppression, or a combination of these pathways. (Cancer Sci 2009; 100: 1779-1785). © 2009 Japanese Cancer Association

External and internal focus of attention differentially modulate corticospinal excitability in anticipatory postural adjustments

Whether attentional focus modulates the corticospinal excitability of the lower limb muscles in anticipatory postural adjustments (APAs) when performing a ballistic movement of the upper limb remains unclear. The present study used transcranial magnetic stimulation (TMS) to examine the corticospinal excitability of the lower limb muscles along with the kinematic profiles during dart throwing with different attentional foci, external focus (EF) and internal focus (IF). In 13 healthy participants, TMS was applied immediately before electromyographic onset of the tibialis anterior (TA) muscle, and the motor evoked potential (MEP) was recorded in the TA and soleus (SOL) muscles. The performance accuracy was significantly higher in the EF condition than in the IF condition. In both EF and IF conditions, MEP amplitude in the TA muscle, but not the SOL muscle, was significantly higher immediately before TA muscle onset (− 100, − 50, and 0 ms) compared to the control. In particular, the MEP increment in the TA muscle before TA muscle onset (− 50 and 0 ms) was significantly larger in the EF condition than in the IF condition. Our findings provide the first evidence for the modulation of corticospinal excitability in APA by changing attentional focus

Activation of epidermal growth factor receptor signaling by the prostaglandin E2 receptor EP4 pathway during gastric tumorigenesis

金沢大学がん進展制御研究所Cyclooxygenase-2 (COX-2) plays an important role in tumorigenesis through prostaglandin E2 (PGE2) biosynthesis. It has been shown by in vitro studies that PGE2 signaling transactivates epidermal growth factor receptor (EGFR) through an intracellular mechanism. However, the mechanisms underlying PGE2-induced EGFR activation in in vivo tumors are still not fully understood. We previously constructed transgenic mice that develop gastric tumors caused by oncogenic activation and PGE2 pathway induction. Importantly, expression of EGFR ligands, epiregulin, amphiregulin, heparin-binding EGF-like growth factor, and betacellulin, as well as a disintegrin and metalloproteinases (ADAMs), ADAM8, ADAM9, ADAM10, and ADAM17 were significantly increased in the mouse gastric tumors in a PGE2 pathway-dependent manner. These ADAMs can activate EGFR by ectodomain shedding of EGFR ligands. Notably, the extensive induction of EGFR ligands and ADAMs was suppressed by inhibition of the PGE2 receptor EP4. Moreover, EP4 signaling induced expression of amphiregulin and epiregulin in activated macrophages, whereas EP4 pathway was required for basal expression of epiregulin in gastric epithelial cells. In contrast, ADAMs were not induced directly by PGE2 in these cells, suggesting indirect mechanism possibly through PGE2-associated inflammatory responses. These results suggest that PGE2 signaling through EP4 activates EGFR in gastric tumors through global induction of EGFR ligands and ADAMs in several cell types either by direct or indirect mechanism. Importantly, gastric tumorigenesis of the transgenic mice was significantly suppressed by combination treatment with EGFR and COX-2 inhibitors. Therefore, it is possible that inhibition of both COX-2/PGE2 and EGFR pathways represents an effective strategy for preventing gastric cancer. © 2011 Japanese Cancer Association

Prostaglandin E2 signaling and bacterial infection recruit tumor-promoting macrophages to mouse gastric tumors

金沢大学がん研究所Background & Aims Helicobacter pylori infection induces an inflammatory response, which can contribute to gastric tumorigenesis. Induction of cyclooxygenase-2 (COX-2) results in production of prostaglandin E2 (PGE2), which mediates inflammation. We investigated the roles of bacterial infection and PGE2 signaling in gastric tumorigenesis in mice. Methods We generated a germfree (GF) colony of K19-Wnt1/C2mE mice (Gan mice); these mice develop gastric cancer. We examined tumor phenotypes, expression of cytokines and chemokines, and recruitment of macrophages. We also investigated PGE2 signaling through the PGE2 receptor subtype 4 (EP4) in Gan mice given specific inhibitors. Results Gan mice raised in a specific pathogen-free facility developed large gastric tumors, whereas gastric tumorigenesis was significantly suppressed in GF-Gan mice; reconstitution of commensal flora or infection with Helicobacter felis induced gastric tumor development in these mice. Macrophage infiltration was significantly suppressed in the stomachs of GF-Gan mice. Gan mice given an EP4 inhibitor had decreased expression of cytokines and chemokines. PGE2 signaling and bacterial infection or stimulation with lipopolysaccharide induced expression of the chemokine C-C motif ligand 2 (CCL2) (which attracts macrophage) in tumor stromal cells or cultured macrophages, respectively. CCL2 inhibition suppressed macrophage infiltration in tumors, and depletion of macrophages from the tumors of Gan mice led to signs of tumor regression. Wnt signaling was suppressed in the tumors of GF-Gan and Gan mice given injections of tumor necrosis factor-α neutralizing antibody. Conclusions Bacterial infection and PGE2 signaling are required for gastric tumorigenesis in mice; they cooperate to up-regulate CCL2, which recruits macrophage to gastric tumors. Macrophage-derived tumor necrosis factor-α promotes Wnt signaling in epithelial cells, which contributes to gastric tumorigenesis. © 2011 AGA Institute

歯科インプラント周囲の骨吸収に関する臨床疫学研究

Background: During functional loading, the design of the dental implant may have an effect on the response of marginal bone. Objectives: The purpose of this study was to report the prevalence of peri-implantitis, and to compare radiographic parameters around Brånemark and Replace Select dental implants and evaluate whether disparities in the morphologic features of these two indistinct implant systems, particularly their abutment-implant attachment, had an influence on the health of surrounding tissues and marginal bone loss (MBL). Materials and Methods: Collection of data was done at the Department of Fixed Prosthodontics, the Department of Maxillo-Facial Prosthodontics, and Oral Implant Center of Tokushima University Hospital, in Tokushima, Japan; between March 2003 and followed until January 2017. Patients who have been treated with the Replace Select internal type implant and the Brånemark variety were selected as cohort. Marginal bone level measurements were evaluated via periapical and panoramic radiographs taken at regular follow-up visit. These dimensions were calculated, starting from the orientation mark at the implant abutment interface to the bottommost perceived contact area of marginal bone with the aforementioned implant system. The change in the level of bone was estimated by calculating the variation involving an initial reference value and the follow-up values. Results: An average loss of bone at 0.65 ± 1.51 mm (range 0.36 to 7.89 mm) in the Replace Select group was observed, while in the Brånemark group 0.7 ± 1.32 mm (range 0.62 to 8.64 mm) was observed. Spearman rank correlation exhibited a statistically significant positive correlation between progress of bone loss around implant body and interval from implantation in the Brånemark group, whereas in the Replace Select group it was not significant. The Brånemark group exhibited significant (P = 0.0269) negative correlation of MBL and its diameters, whereas the Replace Select group did not exhibit such correlation. Conclusion: Within the limits of this study, it can be concluded that deviations in the morphologic attributes of these two diverse implant systems had an influence on the health of surrounding tissues and MBL. The Brånemark implants showed a significant increase in MBL (> 1.8mm) as the time of placement elapses. This marked MBL was greater in females than males, in posterior than in anterior, and in the narrow platform implants than the regular platform implants or the wide platform implants. On the other hand, results suggested that this bone loss was greater in the mandible than the maxilla, in single-unit implant crowns than multiple implant restorations in the Replace Select group

Three-dimensional Structure of Nylon Hydrolase and Mechanism of Nylon-6 Hydrolysis

This research was originally published in the Journal of Biological Chemistry. Seiji Negoro, Naoki Shibata, Yusuke Tanaka, Kengo Yasuhira, Hiroshi Shibata, Haruka Hashimoto, Young-Ho Lee, Shohei Oshima, Ryuji Santa, Shohei Oshima, Kozo Mochiji, Yuji Goto, Takahisa Ikegami, Keisuke Nagai, Dai-ichiro Kato, Masahiro Takeo and Yoshiki Higuchi. Three-dimensional Structure of Nylon Hydrolase and Mechanism of Nylon-6 Hydrolysis. J. Biol. Chem. 2012; 287, 5079-5090. © the American Society for Biochemistry and Molecular Biolog