Enhancement of the antigen-specific cytotoxic T lymphocyte-inducing ability in the PMDC11 leukemic plasmacytoid dendritic cell line via lentiviral vector-mediated transduction of the caTLR4 gene.

The aim of the present study was to enhance the efficiency of leukemia immunotherapy by increasing the antigen-specific cytotoxic T lymphocyte-inducing ability of leukemia cells. The leukemic plasmacytoid dendritic cell line PMDC05 containing the HLA-A02/24 antigen, which was previously established in our laboratory (Laboratory of Hematology and Oncology, Graduate School of Health Sciences, Niigata University, Niigata, Japan), was used in the present study. It exhibited higher expression levels of CD80 following transduction with lentiviruses encoding the CD80 gene. This CD80-expressing PMDC05 was named PMDC11. In order to establish a more potent antigen-presenting cell for cellular immunotherapy of tumors or severe infections, PMDC11 cells were transduced with a constitutively active (ca) toll-like receptor 4 (TLR4) gene using the Tet-On system (caTLR4-PMDC11). CD8(+) T cells from healthy donors with HLA-A02 were co-cultured with mutant WT1 peptide-pulsed PMDC11, lipopolysaccharide (LPS)-stimulated PMDC11 or caTLR4-PMDC11 cells. Interleukin (IL)-2 (50 IU/ml) and IL-7 (10 ng/ml) were added on day three of culture. Priming with mutant WT1 peptide-pulsed PMDC11, LPS-stimulated PMDC11 or caTLR4-PMDC11 cells was conducted once per week and two thirds of the IL-2/IL-7 containing medium was replenished every 3-4 days. Immediately prior to the priming with these various PMDC11 cells, the cultured cells were analyzed for the secretion of interferon (IFN)-γ in addition to the percentage and number of CD8(+)/WT1 tetramer(+) T cells using flow cytometry. caTLR4-PMDC11 cells were observed to possess greater antigen-presenting abilities compared with those of PMDC11 or LPS-stimulated PMDC11 cells in a mixed leukocyte culture. CD8 T cells positive for the WT1 tetramer were generated following 3-4 weeks of culture and CD8(+)/WT1 tetramer+ T cells were markedly increased in caTLR4-PMDC11-primed CD8(+) T cell culture compared with PMDC11 or LPS-stimulated PMDC11-primed CD8(+) T cell culture. These CD8(+) T cells co-cultured with caTLR4-PMDC11 cells were demonstrated to secrete IFN-γ and to be cytotoxic to WT1-expressing target cells. These data suggested that the antigen-specific cytotoxic T lymphocyte (CTL)-inducing ability of PMDC11 was potentiated via transduction of the caTLR4 gene. The present study also suggested that caTLR4-PMDC11 cells may be applied as potent antigen-presenting cells for generating antigen-specific CTLs in adoptive cellular immunotherapy against tumors and severe viral infections

Thermodynamic determination of the equilibrium first-order phase-transition line hidden by hysteresis in a phase diagram

Phase diagrams form the basis for the study of material science, and the profiles of phase-transition lines separating different thermodynamic phases include comprehensive information about thermodynamic quantities, such as latent heat. However, in some materials exhibiting field-induced first-order transitions (FOTs), the equilibrium phase-transition line is hidden by the hysteresis region associated with the FOT; thus, it cannot be directly determined from measurements of resistivity, magnetization, etc. Here, we demonstrate a thermodynamics-based method for determining the hidden equilibrium FOT line. This method is verified for the FOT between antiferromagnetic and ferrimagnetic states in magneto-electric compounds (Fe$_{0.95}$Zn$_{0.05}$)$_{2}$Mo$_{3}$O$_{8}$. The equilibrium FOT line determined based on the Clausius-Clapeyron equation exhibits a reasonable profile in terms of the third law of thermodynamics, and it shows marked differences from the midpoints of the hysteresis region. Our findings highlight that care should be taken for referring to the hysteresis midpoint line when discussing field-induced latent heat or magnetocaloric effects.Comment: 22 pages, 7 figure

Association between the rs1465040 single-nucleotide polymorphism close to the transient receptor potential subfamily C member 3 (TRPC3) gene and postoperative analgesic requirements

AbstractAn association between postoperative analgesic requirements in subjects who underwent orthognathic surgery and the rs1465040 single-nucleotide polymorphism close to the transient receptor potential subfamily C member 3 (TRPC3) gene was suggested by our previous genome-wide association study. To verify this association, we analyzed the association between the rs1465040 SNP and analgesic requirements, including opioid requirements, after open abdominal surgery. The association between the rs1465040 SNP and postoperative analgesic requirements was confirmed in the open abdominal surgery group (P = 0.036), suggesting that the TRPC3 SNP may contribute to predicting postoperative analgesic requirements

A novel efficient feeder-free culture system for the derivation of human induced pluripotent stem cells

Nakagawa, M.et al. A novel efficient feeder-free culture system forthe derivation of human induced pluripotent stem cells.Sci. Rep.4, 3594; DOI:10.1038/srep03594 (2014)

The Japanese space gravitational wave antenna; DECIGO

DECi-hertz Interferometer Gravitational wave Observatory (DECIGO) is the future Japanese space gravitational wave antenna. DECIGO is expected to open a new window of observation for gravitational wave astronomy especially between 0.1 Hz and 10 Hz, revealing various mysteries of the universe such as dark energy, formation mechanism of supermassive black holes, and inflation of the universe. The pre-conceptual design of DECIGO consists of three drag-free spacecraft, whose relative displacements are measured by a differential Fabry– Perot Michelson interferometer. We plan to launch two missions, DECIGO pathfinder and pre- DECIGO first and finally DECIGO in 2024

DECIGO pathfinder

DECIGO pathfinder (DPF) is a milestone satellite mission for DECIGO (DECi-hertz Interferometer Gravitational wave Observatory) which is a future space gravitational wave antenna. DECIGO is expected to provide us fruitful insights into the universe, in particular about dark energy, a formation mechanism of supermassive black holes, and the inflation of the universe. Since DECIGO will be an extremely large mission which will formed by three drag-free spacecraft with 1000m separation, it is significant to gain the technical feasibility of DECIGO before its planned launch in 2024. Thus, we are planning to launch two milestone missions: DPF and pre-DECIGO. The conceptual design and current status of the first milestone mission, DPF, are reviewed in this article

Current status of space gravitational wave antenna DECIGO and B-DECIGO

Deci-hertz Interferometer Gravitational Wave Observatory (DECIGO) is the future Japanese space mission with a frequency band of 0.1 Hz to 10 Hz. DECIGO aims at the detection of primordial gravitational waves, which could be produced during the inflationary period right after the birth of the universe. There are many other scientific objectives of DECIGO, including the direct measurement of the acceleration of the expansion of the universe, and reliable and accurate predictions of the timing and locations of neutron star/black hole binary coalescences. DECIGO consists of four clusters of observatories placed in the heliocentric orbit. Each cluster consists of three spacecraft, which form three Fabry-Perot Michelson interferometers with an arm length of 1,000 km. Three clusters of DECIGO will be placed far from each other, and the fourth cluster will be placed in the same position as one of the three clusters to obtain the correlation signals for the detection of the primordial gravitational waves. We plan to launch B-DECIGO, which is a scientific pathfinder of DECIGO, before DECIGO in the 2030s to demonstrate the technologies required for DECIGO, as well as to obtain fruitful scientific results to further expand the multi-messenger astronomy.Comment: 10 pages, 3 figure