TLR7 mediated viral recognition results in focal type I interferon secretion by dendritic cells.

Plasmacytoid dendritic cells (pDC) sense viral RNA through toll-like receptor 7 (TLR7), form self-adhesive pDC-pDC clusters, and produce type I interferons. This cell adhesion enhances type I interferon production, but little is known about the underlying mechanisms. Here we show that MyD88-dependent TLR7 signaling activates CD11a/CD18 integrin to induce microtubule elongation. TLR7+ lysosomes then become linked with these microtubules through the GTPase Arl8b and its effector SKIP/Plekhm2, resulting in perinuclear to peripheral relocalization of TLR7. The type I interferon signaling molecules TRAF3, IKKα, and mTORC1 are constitutively associated in pDCs. TLR7 localizes to mTORC1 and induces association of TRAF3 with the upstream molecule TRAF6. Finally, type I interferons are secreted in the vicinity of cell-cell contacts between clustered pDCs. These results suggest that TLR7 needs to move to the cell periphery to induce robust type I interferon responses in pDCs.

Comparative analysis on inactivation kinetics of between piezotolerant and piezosensitive mutant strains of Saccharomyces cerevisiae under combinations of high hydrostatic pressure and temperature.

We previously obtained a pressure-tolerant (piezotolerant) and a pressure sensitive (piezosensitive) mutant strain, under ambient temperature, from Saccharomyces cerevisiae strain KA31a. The inactivation kinetics of these mutants were analyzed at 150 to 250MPa with 4 to 40°C. By a multiple regression analysis, the pressure and temperature dependency of the inactivation rate constants k values of both mutants, as well as the parent strain KA31a, were well approximated with high correlation coefficients (0.92 to 0.95). For both mutants, as well as strain KA31a, the lowest k value was shown at a low pressure levels with around ambient temperature. The k value approximately increased with increase in pressure level, and with increase and decrease in temperature. The piezosensitive mutant strain a924E1 showed piezosensitivity at all pressure and temperature levels, compared with the parent strain KA31a. In contrast, the piezotolerant mutant strain a2568D8 showed piezotolerance at 4 to 20°C, but did not show significant piezotolerance at 40°C. These results of the variable influence of temperature on pressure inactivation of these strains would be important for better understanding of piezosensitive and piezotolerant mechanisms, as well as the pressure inactivation mechanism of S. cerevisiae.

Effect of high pressure on the saccharification of starch in the tuberous root of sweet potato (Ipomoea batatas).

We analyzed the effect of high hydrostatic pressure (HHP) treatment on reducing sugar production in the tuberous root of sweet potato (Ipomoea batatas), based on pressure-gelatinization of starch and subsequent saccharification by internal amylases. HHP treatment at up to 600MPa at ambient temperature for 10min did not apparently affect the reducing sugar concentration in tuberous root. However, HHP treatment at 100 to 500MPa and 60°C or 70°C for 10min increased reducing sugar concentration as both the pressure and temperature increased. The reducing sugar concentration after HHP treatment at 500MPa and 70°C for 10min was roughly comparable to that of the thermal treatment control (80°C for 10min under atmospheric pressure). HHP treatment enabled the gelatinization and enzymatic saccharification of starch in the tuberous root of sweet potato, at a lower temperature than required by thermal treatment at atmospheric pressure.

Successful low-dose radiotherapy treatment for Kasabach-Merritt syndrome.

Kasabach-Merritt syndrome (KMS) is characterized by hemangioma associated with life-threatening thrombocytopenia, and is a consumptive coagulopathy. Although treatments available include corticosteroids, α-interferon, vincristine, and surgery, response may be unsatisfactory, and the mortality rate remains at approximately 30%. Although radiotherapy has been used effectively for KMS, it may cause growth retardation and secondary malignancy. We report a case of KMS in which hemangioma of the left thigh was successfully treated with low-dose radiotherapy (6 Gy in six fractions, weekly) after failure of corticosteroid therapy. No significant late effects due to the radiotherapy were noted at 5 year follow up. Thus, low-dose radiotherapy remains an important treatment method for KMS when patients fail to respond to other treatments.

Japan's long-term care policy for older people: the emergence of innovative "mobilisation" initiatives following the 2005 reforms.

Japan leads the global race for solutions to the increasing long-term care demand from an ageing population. Initial responses in 2000 saw the launch of the public Long-Term Care Insurance (LTCI) system which witnessed an unexpectedly substantial uptake - with doubts raised about financial viability and sustainability. The post-2005 LTCI reform led to the adoption of innovations - including the "mobilisation" of active, older volunteers to support their frailer peers. This strategy, within the wider government's "2025 Vision" to provide total care for the entire older population, sought to secure financial viability and sustainability. Drawing on qualitative in-depth interviews with 21 provider organisations this study will examine three "mobilisation" schemes and identify those factors contributing to overall strengths while acknowledging complexities, diversities and challenges the schemes encountered. Initial literature written by mobilisation proponents may have been overly optimistic: this study seeks to balance such views through providing an understanding and analysis of these mobilisation schemes' realities. The findings will provide insights and suggest more caution to policy-makers intending to promote such schemes - in both Japan and in countries considering doing so. Furthermore, more evaluation is required to obtain evidence to support financial feasibility and sustainability.

Effects of High Hydrostatic Pressure on Water Absorption of Adzuki Beans.

The effect of high hydrostatic pressure (HHP) treatment on dried soybean, adzuki bean, and kintoki kidney bean, which are low-moisture-content cellular biological materials, was investigated from the viewpoint of water absorption. The samples were vacuum-packed with distilled water and pressurized at 200 MPa and 25 °C for 10 min. After the HHP treatment, time courses of the moisture contents of the samples were measured, and the dimensionless moisture contents were estimated. Water absorption in the case of soybean could be fitted well by a simple water diffusion model. High pressures were found to have negligible effects on water absorption into the cotyledon of soybean and kintoki kidney bean. A non-linear least square method based on the Weibull equation was applied for the adzuki beans, and the effective water diffusion coefficient was found to increase significantly from 8.6 × 10-13 to 6.7 × 10-10 m²/s after HHP treatment. Approximately 30% of the testa of the adzuki bean was damaged upon HHP treatment, which was comparable to the surface area of the testa in the partially peeled adzuki bean sample. Thus, HHP was confirmed to promote mass transfer to the cotyledon of legumes with a tight testa.

Clofarabine-based combination chemotherapy for relapse and refractory childhood acute lymphoblastic leukemia.

Clofarabine, one of the key treatment agents for refractory and relapsed acute lymphoblastic leukemia (ALL), achieves a remission rate of approximately 30% with single-agent clofarabine induction chemotherapy. However, a remission rate of approximately 50% was reported with a combination chemotherapy regimen consisting of clofarabine, etoposide, and cyclophosphamide. We treated two cases with refractory and relapsed ALL with combination chemotherapy including clofarabine; one was an induction failure but the other achieved remission. Both cases developed an infectious complication (NCI-CTCAE grade 3) and body pain with infusion. Prophylactic antibiotic and opioid infusions facilitated avoiding septic shock and pain. Further investigation of such cases is required.

Proteomic analysis of the SIRT6 interactome: novel links to genome maintenance and cellular stress signaling.

The chromatin regulatory factor SIRT6 plays pivotal roles in metabolism, tumor suppression, and aging biology. Despite the fundamental roles of SIRT6 in physiology and disease, only a handful of molecular and functional interactions of SIRT6 have been reported. Here, we characterize the SIRT6 interactome and identify 80+ novel SIRT6-interacting proteins. The discovery of these SIRT6-associations considerably expands knowledge of the SIRT6 interaction network, and suggests previously unknown functional interactions of SIRT6 in fundamental cellular processes. These include chromatin remodeling, mitotic chromosome segregation, protein homeostasis, and transcriptional elongation. Extended analysis of the SIRT6 interaction with G3BP1, a master stress response factor, uncovers an unexpected role and mechanism of SIRT6 in regulating stress granule assembly and cellular stress resistance.

Enzymatic production of γ-aminobutyric acid in soybeans using high hydrostatic pressure and precursor feeding.

The effects were investigated of the glutamic acid (Glu) substrate concentration on the generation and kinetics of γ-aminobutyric acid (GABA) in soybeans treated under high hydrostatic pressure (HHP; 200 MPa for 10 min at 25 °C). The conversion of Glu to GABA decreased with increasing initial Glu concentration in the soybeans. The crude glutamate decarboxylase (GAD) obtained from the HHP-treated soybeans showed substrate inhibition. The GABA production rate in the HHP-treated soybeans fitted the following substrate inhibition kinetic equation: v0=(VmaxS0)/(Km+S0+(S0)2/Ki). The Km value for the HHP-treated soybeans was significantly higher than that of the untreated soybeans. The Km values in this study show the affinity between Glu and GAD, and indicate that the HHP-treated soybeans had lower affinity between Glu and GAD than the untreated soybeans. GAD extracted from the HHP-treated soybeans showed a similar value to that in the HHP-treated soybeans. The intact biochemical system was so damaged in the HHP-treated soybeans that it showed substrate inhibition kinetics similar to that of the extracted GAD. The combination of HHP and precursor feeding proved to be a novel tool that can be used to increase the concentration of a target component.

High-throughput method for a kinetics analysis of the high-pressure inactivation of microorganisms using microplates.

Using microplates as pressure and cultivation vessels, a high-throughput method was developed for analyzing the high-pressure inactivation kinetics of microorganisms. The loss of viability from a high-pressure treatment, measured based on the growth delay during microplate cultivation, showed reproducibility with the conventional agar plate method and was applicable for the kinetics analysis.

Kinetic analysis of E. coli inactivation by high hydrostatic pressure with salts.

Inactivation of E. coli by high hydrostatic pressure (250 to 400 MPa) with salts was investigated based on kinetic analysis. At concentrations from 0.074 to 0.145 M and from 0.240 to 0.290 M, both the absolute activation volumes and the preexponential factors were similar in KCl, NaCl, and LiCl solutions, suggesting that pressure inactivation is not salt-specific. On the other hand, in the intermediate salt-concentration range of 0.145 to 0.240 M, inactivation kinetics in the presence of the Na(+) and K(+) differed significantly from those in the presence of Li(+) (P < 0.05). In this concentration range, effect of salt stress and osmotic stress differed significantly from those in concentrations below 0.145 M or above 0.240 M. The cellular response to pressure varies with salt type and salt concentration. These novel findings provide important clues to distinguish between salt stress and osmotic stress in the inactivation of E. coli.

The effectiveness of a sex education program facilitating social skills for people with intellectual disability in Japan.

BACKGROUND: Sex education should include social skills, such as those that allow individuals to relate, socialize, and communicate with others, to assist people with intellectual disability (ID) to live life fully in the community. OBJECTIVES: We administered and investigated the effects of a program involving 8 interactive sex education sessions that were aimed at improving the social skills of people with ID. METHODS: Participants were 17 people with ID and 17 control group participants in Japan. The evaluation was conducted with a questionnaire based on KiSS-18 (Kikuchi's Scale of Social Skills: 18 items; Kikuchi, 2007 ). RESULTS: The score of KiSS-18 in the experimental group was 55.4 ± 12.9 before the administration of the program, as compared to a mean of 61.8 ± 13.2 after the program. A significant increase was identified. There was no significant difference between the first and second average score in the control group. CONCLUSION: The sex education program involving social skills training for people with ID had significant effects.

Quality of long-term cryopreserved umbilical cord blood units for hematopoietic cell transplantation.

The aim of this study was to evaluate the quality of long-term cryopreserved umbilical cord blood (CB) units for hematopoietic cell transplantation (HCT). The recovery of the number of total nucleated cell (TNC), hematopoietic progenitor cells (HPCs; CD34+ cells, colony-forming units-granulocyte/macrophages [CFU-GMs]), and the percentage of viable cells, CD34+ CD38- cells, and CD34+ CXCR4+ cells of CB units cryopreserved for 10 years for HCT were examined. Eighteen CB units cryopreserved for 10 years (as the study group) and for 1 month (as the control group), respectively, were analyzed. The recovery rate of TNC, CD34+ cells and CFU-GMs were 88.72 ± 16.40, 68.39 ± 18.37 and 42.28 ± 38.16% for the study group and 80.17 ± 14.46, 72.67 ± 20.38 and 49.61 ± 36.39% for the control group (p = 0.106, p = 0.513 and p = 0.559, respectively). There were no significant differences in the recovery rate of TNC, CD34+ cells and CFU-GMs between the study group and the control group. The mean basal percentage of viable cells, CD34+ CD38- cells, and CD34+ CXCR4+ cells after thawing were 83.69 ± 9.45, 9.11 ± 4.13 and 81.65 ± 10.82% for the study group. These results indicate that long-term cryopreservation does not negatively affect the quality of CB units for HCT.

Generation of free amino acids and gamma-aminobutyric acid in water-soaked soybean by high-hydrostatic pressure processing.

The effects of high-hydrostatic pressure processing (HPP) on soybean cotyledon as a cellular biological material were investigated from the viewpoints of the cell structure and enzyme reaction system. Damage to cell structure was evaluated by measuring dielectric properties using the Cole-Cole arc, the radius of which decreased as pressure level increased. Results suggested that cell structure was damaged by HPP. The distribution of free amino acids was measured after HPP (200 MPa) of soybean soaked in water or sodium glutamate (Glu) solution. HPP resulted in high accumulation of free amino acids in water-soaked soybean, due to proteolysis. HPP of soybean in Glu solution caused higher accumulation of gamma-aminobutyric acid, suggesting that both proteolysis and specific Glu metabolism were accelerated by HPP. We concluded that HPP partially degraded cell structure and accelerated biochemical reactions by allowing enzyme activities to remain. These events can be considered "high-pressure induced transformation" of soybean.

Combining living anionic polymerization with branching reactions in an iterative fashion to design branched polymers.

This paper reviews the precise synthesis of many-armed and multi-compositional star-branched polymers, exact graft (co)polymers, and structurally well-defined dendrimer-like star-branched polymers, which are synthetically difficult, by a commonly-featured iterative methodology combining living anionic polymerization with branched reactions to design branched polymers. The methodology basically involves only two synthetic steps; (a) preparation of a polymeric building block corresponding to each branched polymer and (b) connection of the resulting building unit to another unit. The synthetic steps were repeated in a stepwise fashion several times to successively synthesize a series of well-defined target branched polymers.