Uptake of biodegradable poly(γ-glutamic acid) nanoparticles and antigen presentation by dendritic cells in vivo

AbstractPoly(γ-glutamic acid) (γ-PGA) nanoparticles (NPs) carrying antigens have been shown to induce potent antigen-specific immune responses. However, in vivo delivery of γ-PGA NPs to dendritic cells (DCs), a key regulator of immune responses, still remains unclear. In this study, γ-PGA NPs were examined for their uptake by DCs and subsequent migration from the skin to the regional lymph nodes (LNs) in mice. After subcutaneous injection of fluorescein 5-isothiocyanate (FITC)-labeled NPs or FITC-ovalbumin (OVA)-carrying NPs (FITC-OVA-NPs), DCs migrated from the skin to the LNs and maturated, resulting in the upregulation of the costimulatory molecules CD80 and CD86 and the chemokine receptor CCR7. However, the migrated DCs were not detected in the spleen. FITC-OVA-NPs were found to be taken up by skin-derived CD103+ DCs, and the processed antigen peptides were cross-presented by the major histocompatibility complex (MHC) class I molecule of DCs. Furthermore, significant activation of antigen-specific CD8+ T cells was observed in mice immunized with OVA-carrying NPs (OVA-NPs) but not with OVA alone or OVA with an aluminum adjuvant. The antigen-specific CD8+ T cells were induced within 7 days after immunization with OVA-NPs. Thus, γ-PGA NPs carrying various antigens may have great potential as an antigen-delivery system and vaccine adjuvant in vivo

A Theoretical Study of the Insertion of Atoms and Ions into Titanosilsequioxane (Ti-POSS) in Comparison with POSS

The insertion reaction of various guest species, such as rare gases (He, Ne, and Ar), cations of group 1 (Li+, Na+, and K+), and anions of group 17 (F− and Cl−) elements, into the Ti analogues of POSS (polyhedral oligomeric silsesquioxanes), Ti-POSS, [HTiO1.5]n ( and 10), has been investigated by ab initio molecular orbital and density functional methods. For each case, the properties of the exohedral and endohedral complexes and transition-state structure connecting them on the potential energy surface and energetics are discussed in comparison with the case of POSS. Furthermore, in order to understand the origin of the stability of these structures, the binding energy () and the energy barrier of the encapsulation are analyzed by an energy decomposition method. As a result, some similarities and differences between Ti-POSS and POSS were explored

Effect of heat shock preconditioning on ROS scavenging activity in rat skeletal muscle after downhill running

金沢大学附属病院整形外科The mechanisms of the protective effect conferred by heat shock preconditioning (HS) are currently unknown. The purpose of this study was to determine the effect of HS on muscle injury after downhill running and to address the mechanism of the effect. Female Wistar rats were assigned to three groups: HS, downhill running (E), and downhill running after heat shock preconditioning (HS + E). The HS and HS + E rats were placed in a heat chamber for 60 min (ambient temperature 42 ± 1.0°C) 48 h before downhill running. Reactive oxygen species (ROS) scavenging activity was determined by electron spin resonance (ESR), and heat shock protein 72 (HSP72) mRNA expression was measured in rat quadriceps femoris. Leukocyte infiltration and degenerated muscle fibers were determined histopathologically. ROS scavenging activity significantly increased at 3 days after HS (151 ± 18%) and HSP72 mRNA expression increased immediately after HS (1750 ± 1914%). No decrease in ROS scavenging activity was observed in the HS + E rats at 2 days after exercise compared with the E rats (102 ± 9% vs. 79 ± 5%). Degenerated muscle fibers in HS + E rats were significantly less than in E rats at 2, 3, and 7 days after exercise (0.8 ± 1.0 vs. 2.8 ± 1.6, 0.8 ± 1.0 vs. 1.8 ± 1.6, 0 vs. 0.3 ± 0.6, respectively). These data demonstrated that HS can reduce muscle injury after downhill running, and this effect may be mediated by increased ROS scavenging activity. Furthermore, HS may protect the antioxidant defense system in skeletal muscle by enhancing the adaptive HSP72 mRNA response.全文公開20091

Dose Measurements through the Concrete and Iron Shields under the 100 to 400 MeV Quasi-Monoenergetic Neutron Field (at RCNP, Osaka Univ.)

Shielding benchmark experiments are useful to verify the accuracy of calculation methods for the radiation shielding designs of high-energy accelerator facilities. In the present work, the benchmark experiments were carried out for 244- and 387-MeV quasi-monoenergetic neutron field at RCNP of Osaka University. Neutron dose rates through the test shields, 100-300 cm thick concrete and 40-100 cm thick iron, were measured by four kinds of neutron dose equivalent monitors, three kinds of wide-energy range monitors applied to high-energy neutron fields above 20 MeV and a conventional type rem monitor for neutrons up to 20 MeV, placed behind the test shields. Measured dose rates were compared one another. Measured results with the wide-energy range monitors were in agreement one another for both the concrete and the iron shields. For the conventional type rem monitor, measured results are smaller than those with the wide-energy range monitors for the concrete shields, while that are in agreements for the iron shields. The attenuation lengths were obtained from the measurements. The lengths from all the monitors are in agreement on the whole, though some differences are shown. These results are almost same as those from others measured at several hundred MeV neutron fields

Clinical application of scaffolds for cartilage tissue engineering

The purpose of this paper is to review the basic science and clinical literature on scaffolds clinically available for the treatment of articular cartilage injuries. The use of tissue-engineered grafts based on scaffolds seems to be as effective as conventional ACI clinically. However, there is limited evidence that scaffold techniques result in homogeneous distribution of cells. Similarly, few studies exist on the maintenance of the chondrocyte phenotype in scaffolds. Both of which would be potential advantages over the first generation ACI. The mean clinical score in all of the clinical literature on scaffold techniques significantly improved compared with preoperative values. More than 80% of patients had an excellent or good outcome. None of the short- or mid-term clinical and histological results of these tissue-engineering techniques with scaffolds were reported to be better than conventional ACI. However, some studies suggest that these methods may reduce surgical time, morbidity, and risks of periosteal hypertrophy and post-operative adhesions. Based on the available literature, we were not able to rank the scaffolds available for clinical use. Firm recommendations on which cartilage repair procedure is to be preferred is currently not known on the basis of these studies. Randomized clinical trials and longer follow-up periods are needed for more widespread information regarding the clinical effectiveness of scaffold-based, tissue-engineered cartilage repair

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements