The crystal structure of the plant small GTPase OsRac1 reveals its mode of binding to NADPH oxidase

This research was originally published in Journal of Biological Chemistry. Ken-ichi Kosami, Izuru Ohki, Minoru Nagano, Kyoko Furuita, Toshihiko Sugiki, Yoji Kawano, Tsutomu Kawasaki, Toshimichi Fujiwara, Atsushi Nakagawa, Ko Shimamoto and Chojiro Kojima. The crystal structure of the plant small GTPase OsRac1 reveals its mode of binding to NADPH oxidase. Journal of Biological Chemistry. 2014; 289, 28569-28578. © the American Society for Biochemistry and Molecular Biology

Risk-adjusted therapy for pediatric non-T cell ALL improves outcomes for standard risk patients: results of JACLS ALL-02

This study was a second multicenter trial on childhood ALL by the Japan Childhood Leukemia Study Group (JACLS) to improve outcomes in non-T ALL. Between April 2002 and March 2008, 1138 children with non-T ALL were enrolled in the JACLS ALL-02 trial. Patients were stratified into three groups using age, white blood cell count, unfavorable genetic abnormalities, and treatment response: standard risk (SR), high risk (HR), and extremely high risk (ER). Prophylactic cranial radiation therapy (PCRT) was abolished except for CNS leukemia. Four-year event-free survival (4yr-EFS) and 4-year overall survival (4yr-OS) rates for all patients were 85.4% ± 1.1% and 91.2% ± 0.9%, respectively. Risk-adjusted therapy resulted in 4yr-EFS rates of 90.4% ± 1.4% for SR, 84.9% ± 1.6% for HR, and 66.5% ± 4.0% for ER. Based on NCI risk classification, 4yr-EFS rates were 88.2% in NCI-SR and 76.4% in NCI-HR patients, respectively. Compared to previous trial ALL-97, 4yr-EFS of NCI-SR patients was significantly improved (88.2% vs 81.2%, log rank p = 0.0004). The 4-year cumulative incidence of isolated (0.9%) and total (1.5%) CNS relapse were significantly lower than those reported previously. In conclusion, improved EFS in NCI-SR patients and abolish of PCRT was achieved in ALL-02

Development and growth of organs in living whole embryo and larval grafts in zebrafish

Abstract Age-related systemic environments influence neurogenesis and organ regeneration of heterochronic parabiotic partners; however, the difficulty of manipulating small embryos prevents the effects of aged systemic environments on primitive organs at the developmental stage from being analysed. Here, we describe a novel transplantation system to support whole living embryos/larvae as grafts in immunodeficient zebrafish by the intrusion of host blood vessels into the grafts, allowing bodies similar to those of heterochronic parabiosis to be generated by subcutaneous grafting. Although grafted embryos/larvae formed most organs, not all organogenesis was supported equally; although the brain, eyes and the intestine usually developed, the liver, testes and heart developed insufficiently or even occasionally disappeared. Removal of host germ cells stimulated testis development in grafted embryos. These results indicate that primitive testes are susceptible to the systemic environments that originated from the germ cells of aged hosts and imply that the primitive liver and heart are similar. Upon applying this method to embryonic lethal mutants, various types of organs, including testes that developed in germ-cell-removed recipients, and viable offspring were obtained from the mutants. This unique transplantation system will lead to new insights into the age-related systemic environments that are crucial for organogenesis in vertebrates

The Phosphodiesterase 4 Inhibitor Prevents Antigen-induced Biphasic Nasal Obstruction in Brown Norway Rats

Background: Nasal obstruction is considered the most serious problem for patients with allergic rhinitis. We have previously established a model of nasal obstruction in guinea pigs. In the present study, we tried to establish an allergic model of nasal obstruction using Brown Norway (BN) rats to evaluate the effects of phosphodiesterase (PDE) 4 inhibitors in this model. Methods: The volume of the nasal cavity was measured with an acoustic rhinometer. Decrease in the volume of the nasal cavity was taken as nasal obstruction. BN rats were actively sensitized with ovalbumin conjugated with aluminium hydroxide. Intranasal antigen instillation induced biphasic nasal obstruction in sensitized BN rats. Results: Early and late phase responses (EPR and LPR) were observed peaking at 0.5 and 6 hours after the antigen challenge, respectively. Chlorpheniramine did not inhibit EPR or LPR at 10 mg/kg, although the dose was sufficient for the compound to exert its anti-histamine activity. Prednisolone inhibited both responses at 30 mg/kg. Rolipram and CDP-840, PDE4 inhibitors, inhibited both responses at 100 mg/kg. KF19514, a PDE1/4 dual inhibitor, inhibited EPR at 0.1 mg/kg or more and inhibited LPR at 10 mg/kg. Conclusions: The present study provides a simple model of allergic biphasic nasal obstruction in BN rats, and also suggests that the PDE4 inhibitor may alleviate nasal obstruction in patients with allergic rhinitis

Antimicrobial photodynamic activity and cytocompatibility of Au25(Capt)18 clusters photoexcited by blue LED light irradiation

Antimicrobial photodynamic therapy (aPDT) has beneficial effects in dental treatment. We applied captopril-protected gold (Au25(Capt)18) clusters as a novel photosensitizer for aPDT. Photoexcited Au clusters under light irradiation generated singlet oxygen (1O2). Accordingly, the antimicrobial and cytotoxic effects of Au25(Capt)18 clusters under dental blue light-emitting diode (LED) irradiation were evaluated. 1O2 generation of Au25(Capt)18 clusters under blue LED irradiation (420–460 nm) was detected by a methotrexate (MTX) probe. The antimicrobial effects of photoexcited Au clusters (0, 5, 50, and 500 μg/mL) on oral bacterial cells, such as Streptococcus mutans, Aggregatibacter actinomycetemcomitans, and Porphyromonas gingivalis, were assessed by morphological observations and bacterial growth experiments. Cytotoxicity testing of Au clusters and blue LED irradiation was then performed against NIH3T3 and MC3T3-E1 cells. In addition, the biological performance of Au clusters (500 μg/mL) was compared to an organic dye photosensitizer, methylene blue (MB; 10 and 100 μg/mL). We confirmed the 1O2 generation ability of Au25(Capt)18 clusters through the fluorescence spectra of oxidized MTX. Successful application of photoexcited Au clusters to aPDT was demonstrated by dose-dependent decreases in the turbidity of oral bacterial cells. Morphological observation revealed that application of Au clusters stimulated destruction of bacterial cell walls and inhibited biofilm formation. Aggregation of Au clusters around bacterial cells was fluorescently observed. However, photoexcited Au clusters did not negatively affect the adhesion, spreading, and proliferation of mammalian cells, particularly at lower doses. In addition, application of Au clusters demonstrated significantly better cytocompatibility compared to MB. We found that a combination of Au25(Capt)18 clusters and blue LED irradiation exhibited good antimicrobial effects through 1O2 generation and biosafe characteristics, which is desirable for aPDT in dentistry