208 research outputs found

    PreBI: prediction of biological interfaces of proteins in crystals

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    PreBI is a server that predicts biological interfaces in protein crystal structures, according to the complementarity and the area of the interface. The server accepts a coordinate file in the PDB format, and all of the possible interfaces are generated automatically, according to the symmetry operations given in the coordinate file. For all of the interfaces generated, the complementarities of the electrostatic potential, hydrophobicity and shape of the interfaces are analyzed, and the most probable biological interface is identified according to the combination of the degree of complementarity derived from the database analyses and the area of the interface. The results can be checked through an interactive viewer, and the most probable complex can be downloaded as atomic coordinates in the PDB format. PreBI is available at

    Class I/II hybrid inhibitory oligodeoxynucleotide exerts Th1 and Th2 double immunosuppression

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    We designed class I/II hybrid inhibitory oligodeoxynucleotides (iODNs), called iSG, and found that the sequence 5′-TTAGGG-3′, which has a six-base loop head structure, and a 3′-oligo (dG)3–5 tail sequence are important for potent immunosuppressive activity. Interestingly, splenocytes isolated from ovalbumin (OVA)-immunized mice and treated with iSG3 showed suppression of not only interleukin (IL)-6, IL-12p35, IL-12p40, and interferon (IFN) γ mRNA expression, but also IL-4 and IL-13 mRNA expression. Thus, both Th2 and Th1 immune responses can be strongly suppressed by iODNs in splenocytes from allergen-immunized mice, suggesting usefulness in the treatment of diseases induced by over-active immune activation.ArticleFEBS Open Bio. 3:41-45 (2013)journal articl

    Defect of Adaptation to Hypoxia in Patients With COPD Due to Reduction of Histone Deacetylase 7

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    BackgroundHypoxia inducible factor (HIF)-1 plays an important role in cellular adaptation to hypoxia by activating oxygen-regulated genes such as vascular endothelial growth factor (VEGF) and erythropoietin. Sputum VEGF levels are reported to be decreased in COPD, despite hypoxia. Here we show that patients with COPD fail to induce HIF-1α and VEGF under hypoxic condition because of a reduction in histone deacetylase (HDAC) 7.MethodsPeripheral blood mononuclear cells (PBMCs) were obtained from patients with moderate to severe COPD (n = 21), smokers without COPD (n = 12), and nonsmokers (n = 15). PBMCs were exposed to hypoxia (1% oxygen, 5% CO2, and 94% N2) for 24 h, and HIF-1α and HDAC7 protein expression in nuclear extracts were determined by sodium dodecyl sulfate poly acrylamide gel electrophoresis (SDS-PAGE)/Western blotting.ResultsHIF-1α was significantly induced by hypoxia in each group when compared with the normoxic condition (12-fold induction in nonsmokers, 24-fold induction in smokers without COPD, fourfold induction in COPD), but induction of HIF-1α under hypoxia was significantly lower in patients with COPD than in nonsmokers and smokers without COPD (P < .05 and P < .01, respectively). VEGF messenger RNA detected by quantitative real-time polymerase chain reaction was correlated with HIF-1α protein in nuclei (r = 0.79, P < .05), and HDAC7 protein expression was correlated with HIF-1α protein in nuclei (r = 0.46, P < .05). HDAC7 knockdown inhibited hypoxia-induced HIF-1α activity in U937 cells, and HIF-1α nuclear translocation and HIF-1α binding to the VEGF promoter in A549 cells.ConclusionsHDAC7 reduction in COPD causes a defect of HIF-1α induction response to hypoxia with impaired VEGF gene expression. This poor cellular adaptation might play a role in the pathogenesis of COPD

    Root PRR7 improves the accuracy of the shoot circadian clock through nutrient transport

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    The circadian clock allows plants to anticipate and adapt to periodic environmental changes. Organ- and tissue-specific properties of the circadian clock and shoot-to-root circadian signaling have been reported. While this long-distance signaling is thought to coordinate physiological functions across tissues, little is known about the feedback regulation of the root clock on the shoot clock in the hierarchical circadian network. Here, we show that the plant circadian clock conveys circadian information between shoots and roots through sucrose and K⁺. We also demonstrate that K+ transport from roots suppresses the variance of period length in shoots and then improves the accuracy of the shoot circadian clock. Sucrose measurements and qPCR showed that root sucrose accumulation was regulated by the circadian clock. Furthermore, root circadian clock genes, including PSEUDO-RESPONSE REGULATOR7 (PRR7), were regulated by sucrose, suggesting the involvement of sucrose from the shoot in the regulation of root clock gene expression. Therefore, we performed time-series measurements of xylem sap and micrografting experiments using prr7 mutants and showed that root PRR7 regulates K⁺ transport and suppresses variance of period length in the shoot. Our modeling analysis supports the idea that root-to-shoot signaling contributes to the precision of the shoot circadian clock. We performed micrografting experiments that illustrated how root PRR7 plays key roles in maintaining the accuracy of shoot circadian rhythms. We thus present a novel directional signaling pathway for circadian information from roots to shoots and propose that plants modulate physiological events in a timely manner through various timekeeping mechanisms

    Structural valve deterioration of a mitral Carpentier-Edwards pericardial bioprosthesis in an 87-year-old woman 16 years after its implantation

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    The second-generation pericardial valve, the Carpentier-Edwards perimount bioprosthetic (CEP) valve, shows dramatically improved durability as compared to the first-generation pericardial valve, and excellent performance has been obtained, in both the aortic and mitral positions. Especially in elderly patients with an implanted CEP valve, reoperation due to structural valve deterioration (SVD) is rarely required. Here, we report the case of an 87-year-old woman with an explanted CEP valve in the mitral position due to SVD, 16 years after its implantation

    Thoracoscopic Resection of an Anterior Mediastinal Bronchogenic Cyst

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    We report a very rare case of anterior mediastinal bronchogenic cyst, successfully resected by thoracoscopic surgery. A 78-year-old female was noted as having an abnormal shadow on her chest X-ray during a routine medical checkup. Chest CT revealed a cystic tumor in the anterior mediastinum. A thymic cyst was suspected after a detailed examination and thoracoscopic surgery was performed. A cystic tumor containing yellowish-white mucus measuring 46 × 33 × 19 mm in size was successfully removed. Calcification was also observed in the cyst wall. Pathologically, the tumor was characterized by a ciliated columnar epithelial lining, and was subsequently diagnosed as a bronchogenic cyst. Although they may be rare, bronchogenic cysts should also be considered in the evaluation of cystic tumors in the anterior mediastinum

    How did rehabilitation professionals act when faced with the Great East Japan earthquake and disaster? Descriptive epidemiology of disability and an interim report of the relief activities of the ten Rehabilitation-Related Organizations.

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    Objective: Inter-organizational coordination is important for rehabilitation disaster relief. The 2011 Great East Japan Earthquake and Disaster was unprecedented, being geographically widespread and multifaceted. Faced with the crisis, rehabilitation professionals established the 10 Rehabilitation- Related Organizations of Rehabilitation Support Service (10-RRO). The objectives of this paper are to provide descriptive epidemiology and assess the activities of 10- RRO. Design: Descriptive. Methods: Epidemiological data on disability were collected, mainly from official sources. Relief activities were reviewed from daily reports, and the preparedness, initial response and functioning of 10-RRO were assessed with a questionnaire directed at 36 executives of individual organizations. Results: The disaster was characterized by a very low ratio of injuries to death of 0.372, and an odds ratio of deaths among disabled persons of 2.32. 10-RRO provided relief activities at 3 shelters. The total number of dispatch days ranged from 107 to 146, and the cumulative number of professionals and evacuees served was 1,202 and 7,300, respectively. Support activities included prevention of immobilization, daily life support, environmental improvement and transition to temporary housing. The questionnaire survey revealed poor preparedness, satisfactory initial response and support activities, and problems of data collection and advocacy. Conclusion: The disaster was characterized by minimal trauma and a great need for preventing immobilization. This first collaborative endeavour was successful

    Histone acetylation-independent transcription stimulation by a histone chaperone

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    Histone chaperones are thought to be important for maintaining the physiological activity of histones; however, their exact roles are not fully understood. The physiological function of template activating factor (TAF)-I, one of the histone chaperones, also remains unclear; however, its biochemical properties have been well studied. By performing microarray analyses, we found that TAF-I stimulates the transcription of a sub-set of genes. The transcription of endogenous genes that was up-regulated by TAF-I was found to be additively stimulated by histone acetylation. On performing an experiment with a cell line containing a model gene integrated into the chromosome, TAF-I was found to stimulate the model gene transcription in a histone chaperone activity-dependent manner additively with histone acetylation. TAF-I bound to the core histones and remodeled the chromatin structure independent of the N-terminal histone tail and its acetylation level in vitro. These results suggest that TAF-I remodel the chromatin structure through its interaction with the core domain of the histones, including the histone fold, and this mechanism is independent of the histone acetylation status
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