B cell-derived GABA elicits IL-10⁺ macrophages to limit anti-tumour immunity

GABAを標的とする抗腫瘍免疫機構 --代謝産物を介した免疫細胞間制御の一端を解明--. 京都大学プレスリリース. 2021-11-10.Small, soluble metabolites not only are essential intermediates in intracellular biochemical processes, but can also influence neighbouring cells when released into the extracellular milieu1-3. Here we identify the metabolite and neurotransmitter GABA as a candidate signalling molecule synthesized and secreted by activated B cells and plasma cells. We show that B cell-derived GABA promotes monocyte differentiation into anti-inflammatory macrophages that secrete interleukin-10 and inhibit CD8⁺ T cell killer function. In mice, B cell deficiency or B cell-specific inactivation of the GABA-generating enzyme GAD67 enhances anti-tumour responses. Our study reveals that, in addition to cytokines and membrane proteins, small metabolites derived from B-lineage cells have immunoregulatory functions, which may be pharmaceutical targets allowing fine-tuning of immune responses

The combined effect of the T2DM susceptibility genes is an important risk factor for T2DM in non-obese Japanese: a population based case-control study

<p>Abstract</p> <p>Background</p> <p>Type 2 diabetes mellitus (T2DM) is a complex endocrine and metabolic disorder. Recently, several genome-wide association studies (GWAS) have identified many novel susceptibility loci for T2DM, and indicated that there are common genetic causes contributing to the susceptibility to T2DM in multiple populations worldwide. In addition, clinical and epidemiological studies have indicated that obesity is a major risk factor for T2DM. However, the prevalence of obesity varies among the various ethnic groups. We aimed to determine the combined effects of these susceptibility loci and obesity/overweight for development of T2DM in the Japanese.</p> <p>Methods</p> <p>Single nucleotide polymorphisms (SNPs) in or near 17 susceptibility loci for T2DM, identified through GWAS in Caucasian and Asian populations, were genotyped in 333 cases with T2DM and 417 control subjects.</p> <p>Results</p> <p>We confirmed that the cumulative number of risk alleles based on 17 susceptibility loci for T2DM was an important risk factor in the development of T2DM in Japanese population (<it>P </it>< 0.0001), although the effect of each risk allele was relatively small. In addition, the significant association between an increased number of risk alleles and an increased risk of T2DM was observed in the non-obese group (<it>P </it>< 0.0001 for trend), but not in the obese/overweight group (<it>P </it>= 0.88 for trend).</p> <p>Conclusions</p> <p>Our findings indicate that there is an etiological heterogeneity of T2DM between obese/overweight and non-obese subjects.</p

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

The status of DECIGO

DECIGO (DECi-hertz Interferometer Gravitational wave Observatory) is the planned Japanese space gravitational wave antenna, aiming to detect gravitational waves from astrophysically and cosmologically significant sources mainly between 0.1 Hz and 10 Hz and thus to open a new window for gravitational wave astronomy and for the universe. DECIGO will consists of three drag-free spacecraft arranged in an equilateral triangle with 1000 km arm lengths whose relative displacements are measured by a differential Fabry-Perot interferometer, and four units of triangular Fabry-Perot interferometers are arranged on heliocentric orbit around the sun. DECIGO is vary ambitious mission, we plan to launch DECIGO in era of 2030s after precursor satellite mission, B-DECIGO. B-DECIGO is essentially smaller version of DECIGO: B-DECIGO consists of three spacecraft arranged in an triangle with 100 km arm lengths orbiting 2000 km above the surface of the earth. It is hoped that the launch date will be late 2020s for the present

The Possible Effects of Zinc Supplementation on Postpartum Depression and Anemia

Background and Objectives: The effects of postpartum zinc supplementation are still unclear. Our purpose in this study is to investigate the association between Zn supplementation and postpartum depression, defined by an Edinburgh Postnatal Depression Scale (EPDS) score &ge; 9, and the effect on the hematological status of postpartum women. Materials and Methods: We first investigated whether zinc supplementation affected the perioperative levels of zinc, hemoglobin, and hematocrit in 197 cases who underwent cesarean section and had postpartum anemia. Next, logistic regression analyses were performed on 148 eligible cases to determine the association between zinc supplementation and postpartum depression. Results: Postpartum zinc supplementation significantly improved the status of maternal blood zinc levels and reduced the risk of developing postpartum depression (adjusted odds ratio: 0.249; 95% confidence interval: 0.062&ndash;0.988; p = 0.048). Iron supplementation is a standard and effective strategy for treating anemia; however, the combination of oral iron plus zinc supplementation resulted in slightly significant negative effects on postpartum hemoglobin and hematocrit compared to oral iron supplementation only. Conclusions: Postpartum zinc supplementation causes a significant positive effect on postpartum depression (EPDS score &ge; 9). Zinc supplementation had a negative but transient influence on the hematological status in women with postpartum anemia treated with oral iron supplementation; however, the differences were not clinically significant. Thus, we did not regard it as an adverse effect to be considered, and postpartum zinc supplementation may be viewed as beneficial in postpartum women