Neutron scattering study of dipolar spin ice Ho2Sn2O7: Frustrated pyrochlore magnet

By means of neutron scattering techniques we have investigated the frustrated pyrochlore magnetHo2Sn2O7, which was found to show ferromagnetic spin-ice behavior below T.1.4 K by susceptibilitymeasurements. High-resolution powder neutron diffraction shows no detectable disorder of the lattice, whichimplies the appearance of a random magnetic state solely by frustrated geometry, i.e., the corner sharingtetrahedra. Magnetic inelastic scattering spectra show that Ho magnetic moments behave as an Ising spinsystem at low temperatures and that the spin fluctuation has static character. The system remains in a shortrange-ordered state down to at least T50.4 K. By analyzing the wave-vector dependence of the magneticscattering using a mean-field theory, it is shown that the Ising spins interact via the dipolar interaction.Therefore we conclude that Ho2Sn2O7 belongs to the dipolar-spin-ice family. Slow spin dynamics is exhibitedas thermal hysteresis and time dependence of the magnetic scattering

Donor Treg expansion by liposomal alpha-galactosylceramide modulates Tfh cells and prevents sclerodermatous chronic graft-versus-host disease

Background and Aim: Chronic graft-versus-host disease (cGVHD) is a major cause of nonrelapse morbidity and mortality following hematopoietic stem cell transplantation (HSCT). alpha-Galactosylceramide (alpha-GC) is a synthetic glycolipid that is recognized by the invariant T-cell receptor of invariant natural killer T (iNKT) cells in a CD1d-restricted manner. Stimulation of iNKT cells by alpha-GC leads to the production of not only immune-stimulatory cytokines but also immune-regulatory cytokines followed by regulatory T-cell (Treg) expansion in vivo. Methods: We investigated the effect of iNKT stimulation by liposomal alpha-GC just after transplant on the subsequent immune reconstitution and the development of sclerodermatous cGVHD. Results: Our study showed that multiple administrations of liposomal alpha-GC modulated both host- and donor-derived iNKT cell homeostasis and induced an early expansion of donor Tregs. We also demonstrated that the immune modulation of the acute phase was followed by the decreased levels of CXCL13 in plasma and follicular helper T cells in lymph nodes, which inhibited germinal center formation, resulting in the efficient prevention of sclerodermatous cGVHD. Conclusions: These data demonstrated an important coordination of T- and B-cell immunity in the pathogenesis of cGVHD and may provide a novel clinical strategy for the induction of immune tolerance after allogeneic HSCT

Genomic regions involved in yield potential detected by genome-wide association analysis in Japanese high-yielding rice cultivars

BACKGROUND: High-yielding cultivars of rice (Oryza sativa L.) have been developed in Japan from crosses between overseas indica and domestic japonica cultivars. Recently, next-generation sequencing technology and high-throughput genotyping systems have shown many single-nucleotide polymorphisms (SNPs) that are proving useful for detailed analysis of genome composition. These SNPs can be used in genome-wide association studies to detect candidate genome regions associated with economically important traits. In this study, we used a custom SNP set to identify introgressed chromosomal regions in a set of high-yielding Japanese rice cultivars, and we performed an association study to identify genome regions associated with yield. RESULTS: An informative set of 1152 SNPs was established by screening 14 high-yielding or primary ancestral cultivars for 5760 validated SNPs. Analysis of the population structure of high-yielding cultivars showed three genome types: japonica-type, indica-type and a mixture of the two. SNP allele frequencies showed several regions derived predominantly from one of the two parental genome types. Distinct regions skewed for the presence of parental alleles were observed on chromosomes 1, 2, 7, 8, 11 and 12 (indica) and on chromosomes 1, 2 and 6 (japonica). A possible relationship between these introgressed regions and six yield traits (blast susceptibility, heading date, length of unhusked seeds, number of panicles, surface area of unhusked seeds and 1000-grain weight) was detected in eight genome regions dominated by alleles of one parental origin. Two of these regions were near Ghd7, a heading date locus, and Pi-ta, a blast resistance locus. The allele types (i.e., japonica or indica) of significant SNPs coincided with those previously reported for candidate genes Ghd7 and Pi-ta. CONCLUSIONS: Introgression breeding is an established strategy for the accumulation of QTLs and genes controlling high yield. Our custom SNP set is an effective tool for the identification of introgressed genome regions from a particular genetic background. This study demonstrates that changes in genome structure occurred during artificial selection for high yield, and provides information on several genomic regions associated with yield performance. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-346) contains supplementary material, which is available to authorized users

Reduced dose of PTCy followed by adjuvant alpha-galactosylceramide enhances GVL effect without sacrificing GVHD suppression

Posttransplantation cyclophosphamide (PTCy) has become a popular option for haploidentical hematopoietic stem cell transplantation (HSCT). However, personalized methods to adjust immune intensity after PTCy for each patient's condition have not been well studied. Here, we investigated the effects of reducing the dose of PTCy followed by alpha -galactosylceramide (alpha -GC), a ligand of iNKT cells, on the reciprocal balance between graft-versus-host disease (GVHD) and the graft-versus-leukemia (GVL) effect. In a murine haploidentical HSCT model, insufficient GVHD prevention after reduced-dose PTCy was efficiently compensated for by multiple administrations of alpha -GC. The ligand treatment maintained the enhanced GVL effect after reduced-dose PTCy. Phenotypic analyses revealed that donor-derived B cells presented the ligand and induced preferential skewing to the NKT2 phenotype rather than the NKT1 phenotype, which was followed by the early recovery of all T cell subsets, especially CD4(+)Foxp3(+) regulatory T cells. These studies indicate that alpha -GC administration soon after reduced-dose PTCy restores GVHD-preventing activity and maintains the GVL effect, which is enhanced by reducing the dose of PTCy. Our results provide important information for the development of a novel strategy to optimize PTCy-based transplantation, particularly in patients with a potential relapse risk

Identification of a novel arthritis-associated osteoclast precursor macrophage regulated by FoxM1

Osteoclasts have a unique bone-destroying capacity, playing key roles in steady-state bone remodeling and arthritic bone erosion. Whether the osteoclasts in these different tissue settings arise from the same precursor states of monocytoid cells is presently unknown. Here, we show that osteoclasts in pannus originate exclusively from circulating bone marrow-derived cells and not from locally resident macrophages. We identify murine CX3CR1hiLy6CintF4/80+I-A+/I-E+ macrophages (termed here arthritis-associated osteoclastogenic macrophages (AtoMs)) as the osteoclast precursor-containing population in the inflamed synovium, comprising a subset distinct from conventional osteoclast precursors in homeostatic bone remodeling. Tamoxifen-inducible Foxm1 deletion suppressed the capacity of AtoMs to differentiate into osteoclasts in vitro and in vivo. Furthermore, synovial samples from human patients with rheumatoid arthritis contained CX3CR1+HLA-DRhiCD11c+CD80−CD86+ cells that corresponded to mouse AtoMs, and human osteoclastogenesis was inhibited by the FoxM1 inhibitor thiostrepton, constituting a potential target for rheumatoid arthritis treatment.Hasegawa T., Kikuta J., Sudo T., et al. Identification of a novel arthritis-associated osteoclast precursor macrophage regulated by FoxM1. Nature Immunology 20, 1631 (2019); https://doi.org/10.1038/s41590-019-0526-7

THYROID DYSFUNCTION FOLLOWING ALPHA-INTERFERON TREATMENT FOR CHRONIC HEPATITIS C

In order to evaluate the influnces of IFNα on thyroid function, thyroid-stimulating hormone (TSH), total thyroxine (T4), free T4, tri-iodothyronine (T3), and thyroxine-binding globulin were examined in IFNα-treated 351 patients with chronic hepatitis C before and during therapy. As therapy, either 3 million units (MU) of human lymphoblastoid IFNα or 9MU of recombinant IFNα2a was administrated daily for the initial two weeks followed by three times a week for 22 weeks. There were nine patients showing thyroid dysfunction during IFNα therapy. They consist of one relapse of Graves' disease, one relapse of Hashimoto thyroiditis, one development of apparent thyroid insufficiency from subclinical hypothyroidism, five cases with transient hyperthyroidism and one case with transient hypothyroidism. T4 and T3 levels in most patients who transiently developed thyroid dysfunction were normalized spontaneously after the discontinuation of IFNα. Thyroid-related autoantibodies were positive in 4 patients before IFNα therapy and newly developed in one patient during therapy. Attention should be paid first to the previous histories of autoimmune thyroid diseases and the existence of thyroid-related autoantibodies for the prediction of development of thyroid dysfunction during IFNα therapy. In addition, serial examinations of TSH, T3 and T4 should be also necessary for early detection of transient thyroid dysfunction during IFNα therapy

Prediction of heading date, culm length, and biomass from canopy-height-related parameters derived from time-series UAV observations of rice

Unmanned aerial vehicles (UAVs) are powerful tools for monitoring crops for high-throughput phenotyping. Time-series aerial photography of fields can record the whole process of crop growth. Canopy height (CH), which is vertical plant growth, has been used as an indicator for the evaluation of lodging tolerance and the prediction of biomass and yield. However, there have been few attempts to use UAV-derived time-series CH data for field testing of crop lines. Here we provide a novel framework for trait prediction using CH data in rice. We generated UAV-based digital surface models of crops to extract CH data of 30 Japanese rice cultivars in 2019, 2020, and 2021. CH-related parameters were calculated in a non-linear time-series model as an S-shaped plant growth curve. The maximum saturation CH value was the most important predictor for culm length. The time point at the maximum CH contributed to the prediction of days to heading, and was able to predict stem and leaf weight and aboveground weight, possibly reflecting the association of biomass with duration of vegetative growth. These results indicate that the CH-related parameters acquired by UAV can be useful as predictors of traits typically measured by hand

Advanced Taste Sensors Based on Artificial Lipids with Global Selectivity to Basic Taste Qualities and High Correlation to Sensory Scores

Effective R&D and strict quality control of a broad range of foods, beverages, and pharmaceutical products require objective taste evaluation. Advanced taste sensors using artificial-lipid membranes have been developed based on concepts of global selectivity and high correlation with human sensory score. These sensors respond similarly to similar basic tastes, which they quantify with high correlations to sensory score. Using these unique properties, these sensors can quantify the basic tastes of saltiness, sourness, bitterness, umami, astringency and richness without multivariate analysis or artificial neural networks. This review describes all aspects of these taste sensors based on artificial lipid, ranging from the response principle and optimal design methods to applications in the food, beverage, and pharmaceutical markets

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection