Summary
Regulatory T cells (Tregs) control immune responses by suppressing various inflammatory cells. Tregs in newborn babies may play an important role in preventing excessive immune responses ...during their environmental change. We examined the number and phenotype of Tregs during the neonatal period in 49 newborn babies. Tregs were characterized by flow cytometry using cord blood (CB) and peripheral blood (PB) from the early (7–8 days after birth) and late (2–4 weeks after birth) neonatal periods. CD4+forkhead box protein 3 (FoxP3+) T cells were classified into resting Tregs (CD45RA+FoxP3low), activated Tregs (CD45RA– FoxP3high) and newly activated T cells (CD45RA– FoxP3low). Compared with CB and PB during the late neonatal period, the percentage of Tregs and all Treg subpopulations in the CD4+ lymphocyte population were increased significantly during the early neonatal period. Furthermore, the proportion and absolute number of activated Tregs were increased markedly compared with other Treg subpopulations, such as resting Tregs and newly activated T cells (non‐Tregs), in the early neonatal period. Increased Tregs concomitantly expressed the suppressive molecule cytotoxic T lymphocyte antigen‐4 (CTLA‐4). The up‐regulated expression of chemokine receptor 4 (CCR4) and down‐regulated expression of CCR7 were also observed in expanded Tregs. When cord blood cells were cultured in vitro with CD3 monoclonal antibodies (mAb) for 5 days, CD4+CD45RA–FoxP3high cells were increased significantly during the culture. Thus, the presence of increased activated Tregs in early neonates may play an important role in immunological regulation by suppressing excessive T cell activation caused by the immediate exposure to ubiquitous antigens after birth.
Regulatory T cells increase and may play an important role in immune response to adapt environmental change after birth.
It was predicted that TbCu7-type Sm-Fe powder prepared by the low-temperature reduction-diffusion (LTRD) process using a Li-Ca reductant would contain no residual ɑ-Fe because this reductant would ...not produce the absorbed water that hinders the reaction between Sm and Fe by forming oxychlorides when molten salt is used as the reductant. Contrary to this expectation, a detailed microstructure analysis revealed that a residual phase of unreacted ɑ-Fe existed in some TbCu7-type Sm-Fe particles rather than as separate Fe particles. This residual ɑ-Fe phase was not located in the center of the Sm-Fe particles and was not detected in some Sm-Fe particles, suggesting that the reason for the residual ɑ-Fe phase is inhomogeneous diffusion of Sm into the Fe due to slow diffusion at low temperatures. Although this TbCu7-type Sm-Fe powder contained a small amount of unreacted ɑ-Fe phase, the magnetic properties of the nitride TbCu7-type Sm-Fe were also estimated.
•The possibility synthesizing single-phase TbCu7-type Sm-Fe powder was investigated.•The residual α-Fe phase was smaller than in the case using molten salts.•ɑ-Fe phases are not located in the center of some TbCu7-type Sm-Fe particles.•It is inferred that the reduced Sm was inhomogeneously diffused into the Fe.•The coercivity of the TbCu7-type Sm-Fe-N powder was estimated as Hc = 5.5 MA·m-1
High-energy-resolution X-ray spectroscopy using X-ray microcalorimeters has been widely adopted for high-precision experiments on fundamental science. The technical difficulties come from its use at ...low temperatures and its high sensitivity to the external environment, though many countermeasures have been proposed through the experience of space applications. The limit of the number of pixels of the semiconductor-type X-ray microcalorimeters can be solved by using the transition-edge sensor (TES) superconducting detector. Recently, a study of the strong nuclear force via high-energy-resolution X-ray spectroscopy of kaonic atoms using TES at the J-PARC accelerator facility was successfully performed by the HEATES collaboration. Furthermore, muonic-atom spectroscopy using TES has been demonstrated at the J-PARC muon facility, and a physical experiment to test the electromagnetic force under a strong electric field is ready for commissioning. Material diagnostics at a hard X-ray synchrotron facility have been tested at SPring-8 and resulted in a successful operation for the first time. Other than X-rays, TES has been used as a mass spectrometer for neutral molecules in a cryogenic electrostatic ion ring. The entire design of the experiment is carefully considered to meet the science-specific requirement. We will summarize the latest and future applications of the microcalorimeter and present key technologies, such as digital electronics, data acquisition software, aperture, collimator, mechanical, and electrical interface. Our results will be helpful for other users to design new experiments for fundamental science.
Macrophage colony-stimulating factor (M-CSF) regulates the production, survival and function of macrophages through Fms, the receptor tyrosine kinase. Recently, interleukin-34 (IL-34), which shares ...no sequence homology with M-CSF, was identified as an alternative Fms ligand. Here, we provide the first evidence that these ligands indeed resemble but are not necessarily identical in biological activity and signal activation. In culture systems tested, IL-34 and M-CSF showed an equivalent ability to support cell growth or survival. However, they were different in the ability to induce the production of chemokines such as MCP-1 and eotaxin-2 in primary macrophages, the morphological change in TF-1-fms cells and the migration of J774A.1 cells. Importantly, IL-34 induced a stronger but transient tyrosine phosphorylation of Fms and downstream molecules, and rapidly downregulated Fms. Even in the comparison of active domains, these ligands showed no sequence homology including the position of cysteines. Interestingly, an anti-Fms monoclonal antibody (Mab) blocked both IL-34-Fms and M-CSF-Fms binding, but another MAb blocked only M-CSF-Fms binding. These results suggested that IL-34 and M-CSF differed in their structure and Fms domains that they bound, which caused different bioactivities and signal activation kinetics/strength. Our findings indicate that macrophage phenotype and function are differentially regulated even at the level of the single receptor, Fms.
Patients with autoimmune neutropenia (AIN) showed variational and skewed usages of T cell receptor (TCR)‐Vβ families in CD4+CD25− T cells and CD4+CD25+CD127low T cells, compared to those of control ...subjects.
Summary
Autoimmune neutropenia (AIN) in childhood is characterized by chronic neutropenia and positivity for anti‐neutrophil antibodies, resulting in the excessive destruction of neutrophils. In this study, we investigated the involvement of regulatory T cells (Tregs) in the pathogenesis of AIN in childhood. Tregs have been classified into three subpopulations based on the expressions of CD45RA and forkhead box protein 3 (FoxP3): resting Tregs, activated Tregs and non‐suppressive Tregs. The frequency of activated Tregs (CD4+CD25+FoxP3highCD45RA− T cells) as well as that of total Tregs (CD4+CD25+FoxP3+ T cells) in peripheral blood was significantly decreased in patients with AIN. Analysis of the T cell receptor (TCR)‐Vβ repertoire of CD4+ T cells revealed skewed usages in patients with AIN compared with that observed in age‐matched control subjects. Regarding T cell subsets, the use of four of 24 TCR‐Vβ families in Tregs and one in conventional T cells were increased in patients with AIN. The number of patients with AIN who showed skewed usages of TCR‐Vβ family in conventional and Tregs was significantly higher than that reported in control subjects. When the preference between Tregs and conventional T cells in each TCR‐Vβ family was individually compared, different use was prominently observed in the TCR‐Vβ 9 family in patients with AIN. These results suggest that the quantitative abnormalities of Tregs and the skew of the TCR‐Vβ repertoire in CD4+ T cells, including Tregs and conventional T cells, may be related to autoantibody production through a human neutrophil antigen‐reactive T cell clone.
Optimal filtering is the crucial technique for the data analysis of transition-edge-sensor (TES) calorimeters to achieve their state-of-the-art energy resolutions. Filtering out the ‘bad’ data from ...the dataset is important because it otherwise leads to the degradation of energy resolutions, while it is not a trivial task. We propose a neural network-based technique for the automatic goodness tagging of TES pulses, which is fast and automatic and does not require bad data for training.
Gold nanoparticles have been reported as a possible radio-sensitizer agent in radiation therapy due to their ability to increase energy deposition and subsequent direct damage to cells and DNA within ...their local vicinity. Moreover, this increase in energy deposition also results in an increase of the radiochemical yields. In this work we present, for the first time, an in silico investigation, based on the general purpose Monte Carlo simulation toolkit Geant4, into energy deposition and radical species production around a spherical gold nanoparticle 50nm in diameter via proton irradiation. Simulations were preformed for incident proton energies ranging from 2 to 170MeV, which are of interest for clinical proton therapy.
The K¯N system at threshold is a sensitive testing ground for low energy QCD, especially for the explicit chiral symmetry breaking. Therefore, we have measured the K-series X-rays of kaonic hydrogen ...atoms at the DAΦNE electron–positron collider of Laboratori Nazionali di Frascati, and have determined the most precise values of the strong-interaction energy-level shift and width of the 1s atomic state. As X-ray detectors, we used large-area silicon drift detectors having excellent energy and timing resolution, which were developed especially for the SIDDHARTA experiment. The shift and width were determined to be ϵ1s=−283±36(stat)±6(syst) eV and Γ1s=541±89(stat)±22(syst) eV, respectively. The new values will provide vital constraints on the theoretical description of the low-energy K¯N interaction.
Summary
In patients with postmenopausal osteoporosis, prior osteoporosis treatment affected the bone mineral density increase of following treatment with 12 months of romosozumab, although it did not ...affect that of following treatment with 12 months of denosumab after romosozumab.
Purpose
To investigate the effects of prior osteoporosis treatment on the response to treatment with romosozumab (ROMO) followed by denosumab (DMAb) in patients with postmenopausal osteoporosis.
Methods
In this prospective, observational, multicenter study, treatment-naïve patients (Naïve;
n
= 55) or patients previously treated with bisphosphonates (BP;
n
= 37), DMAb (DMAb;
n
= 45) or teriparatide (TPTD;
n
= 17) (mean age, 74.6 years; T-scores of the lumbar spine LS − 3.2 and total hip TH − 2.6) were switched to ROMO for 12 months, followed by DMAb for 12 months. Bone mineral density (BMD) and serum bone turnover markers were evaluated for 24 months.
Results
A BMD increase was observed at 12 and 24 months in the following patients: Naïve (18.2% and 22.0%), BP (10.2% and 12.1%), DMAb (6.6% and 9.7%), and TPTD (10.8% and 15.0%) (
P
< 0.001 between the groups at both 12 and 24 months) in LS and Naïve (5.5% and 8.3%), BP (2.9% and 4.1%), DMAb (0.6% and 2.2%), and TPTD (4.3% and 5.4%) (
P
< 0.01 between the groups at 12 months and
P
< 0.001 at 24 months) in TH, respectively. The BMD increase in LS from 12 to 24 months was negatively associated with the levels of bone resorption marker at 24 months. Incidences of major fragility fractures for the respective groups were as follows: Naïve (5.5%), BP (16.2%), DMAb (11.1%), and TPTD (5.9%).
Conclusions
Previous treatment affected the BMD increase of following treatment with ROMO, although it did not affect that of following treatment with DMAb after ROMO.
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