Distinct transcriptome architectures underlying lupus establishment and exacerbation.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease involving multiple immune cells. To elucidate SLE pathogenesis, it is essential to understand the dysregulated gene expression pattern linked to various clinical statuses with a high cellular resolution. Here, we conducted a large-scale transcriptome study with 6,386 RNA sequencing data covering 27 immune cell types from 136 SLE and 89 healthy donors. We profiled two distinct cell-type-specific transcriptomic signatures: disease-state and disease-activity signatures, reflecting disease establishment and exacerbation, respectively. We then identified candidate biological processes unique to each signature. This study suggested the clinical value of disease-activity signatures, which were associated with organ involvement and therapeutic responses. However, disease-activity signatures were less enriched around SLE risk variants than disease-state signatures, suggesting that current genetic studies may not well capture clinically vital biology. Together, we identified comprehensive gene signatures of SLE, which will provide essential foundations for future genomic and genetic studies.

Clinical significance of cytomegalovirus (CMV) pp65 antigenemia in the prediction of CMV infection during immunosuppressive therapy for rheumatic disease.

To investigate the risk factors for CMV infection and to clarify the cut-off count of CMV pp65 antigenemia predicting clinical symptoms related to CMV infection in patients with rheumatic disease. We retrospectively analyzed 261 patients with rheumatic disease who were treated with immunosuppressive therapy. CMV infection was defined as positive > 1 CMV-positive cell per two slides (CMV pp65 antigenemia C10/C11). Patients with CMV infection were divided into two groups based on the presence of antiviral treatment for CMV disease. We determined a cut-off value of CMV-positive cells for the diagnosis of CMV disease. CMV infection was observed in 141 cases (54%). In a multivariate analysis, CMV infection was associated with three following factors: Age > 60 years (OR 1.87 [95% CI 1.04-3.36]); lymphocyte counts < 1000/µL (OR 3.34 [95% CI 1.88-6.05]); steroid pulse therapy (OR 2.60 [95% CI 1.27-5.55]). The cut-off level of CMV pp65 antigenemia indicating CMV disease was five positive cells average two slides by using receiver operating characteristic curve analysis (AUC 0.95, sensitivity 0.94, specificity 0.80). Age > 60 years, lymphocytopenia (< 1000/µL) and steroid pulse therapy are risk factors of CMV infection. We recommend that CMV pp65 antigenemia of > 5 cells average two slides (C10/C11) in patients with rheumatic disease should be the treated with antiviral drugs.

Genetic structure of Miscanthus sinensis and Miscanthus sacchariflorus in Japan indicates a gradient of bidirectional but asymmetric introgression.

Unilateral introgression from diploids to tetraploids has been hypothesized to be an important evolutionary mechanism in plants. However, few examples have been definitively identified, perhaps because data of sufficient depth and breadth were difficult to obtain before the advent of affordable high-density genotyping. Throughout Japan, tetraploid Miscanthus sacchariflorus and diploid Miscanthus sinensis are common, and occasionally hybridize. In this study, 667 M. sinensis and 78 M. sacchariflorus genotypes from Japan were characterized using 20 704 SNPs and ten plastid microsatellites. Similarity of SNP genotypes between diploid and tetraploid M. sacchariflorus indicated that the tetraploids originated through autopolyploidy. Structure analysis indicated a gradient of introgression from diploid M. sinensis into tetraploid M. sacchariflorus throughout Japan; most tetraploids had some M. sinensis DNA. Among phenotypically M. sacchariflorus tetraploids, M. sinensis ancestry averaged 7% and ranged from 1-39%, with introgression greatest in southern Japan. Unexpectedly, rare (~1%) diploid M. sinensis individuals from northern Japan were found with 6-27% M. sacchariflorus ancestry. Population structure of M. sinensis in Japan included three groups, and was driven primarily by distance, and secondarily by geographic barriers such as mountains and straits. Miscanthus speciation is a complex and dynamic process. In contrast to limited introgression between diploid M. sacchariflorus and M. sinensis in northern China, selection for adaptation to a moderate maritime climate probably favoured cross-ploidy introgressants in southern Japan. These results will help guide the selection of Miscanthus accessions for the breeding of biomass cultivars.

Effect of Rj genotype and cultivation temperature on the community structure of soybean-nodulating bradyrhizobia.

The nodulation tendency and community structure of indigenous bradyrhizobia on Rj genotype soybean cultivars at cultivation temperatures of 33/28°C, 28/23°C, and 23/18°C for 16/8 h (day/night degrees, hours) were investigated using 780 bradyrhizobial DNA samples from an Andosol with 13 soybean cultivars of four Rj genotypes (non-Rj, Rj(2)Rj(3), Rj(4), and Rj(2)Rj(3)Rj(4)). A dendrogram was constructed based on restriction fragment length polymorphism of the PCR products (PCR-RFLP) of the 16S-23S rRNA gene internal transcribed spacer region. Eleven Bradyrhizobium U.S. Department of Agriculture strains were used as a reference. The dendrogram indicated seven clusters based on similarities among the reference strains. The occupancy rate of the Bj123 cluster decreased with increasing cultivation temperature, whereas the occupancy rates of the Bj110 cluster, Be76 cluster, and Be94 cluster increased with increasing cultivation temperature. In particular, the Rj(2)Rj(3)Rj(4) genotype soybeans were infected with a number of Bj110 clusters, regardless of the increasing cultivation temperature, compared to other Rj genotype soybean cultivars. The ratio of beta diversity to gamma diversity (H'(ß)/H'(γ)), which represents differences in the bradyrhizobial communities by pairwise comparison among cultivation temperature sets within the same soybean cultivar, indicated that the bradyrhizobial communities tended to be different among cultivation temperatures. Multidimensional scaling analysis indicated that the infection of the Bj110 cluster and the Bj123 cluster by host soybean genotype and the cultivation temperature affected the bradyrhizobial communities. These results suggested that the Rj genotypes and cultivation temperatures affected the nodulation tendency and community structures of soybean-nodulating bradyrhizobia.

The differential diagnosis of IgG4-related disease based on machine learning.

INTRODUCTION: To eliminate the disparity and maldistribution of physicians and medical specialty services, the development of diagnostic support for rare diseases using artificial intelligence is being promoted. Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is a rare disorder often requiring special knowledge and experience to diagnose. In this study, we investigated the possibility of differential diagnosis of IgG4-RD based on basic patient characteristics and blood test findings using machine learning. METHODS: Six hundred and two patients with IgG4-RD and 204 patients with non-IgG4-RD that needed to be differentiated who visited the participating institutions were included in the study. Ten percent of the subjects were randomly excluded as a validation sample. Among the remaining cases, 80% were used as training samples, and the remaining 20% were used as test samples. Finally, validation was performed on the validation sample. The analysis was performed using a decision tree and a random forest model. Furthermore, a comparison was made between conditions with and without the serum IgG4 concentration. Accuracy was evaluated using the area under the receiver-operating characteristic (AUROC) curve. RESULTS: In diagnosing IgG4-RD, the AUROC curve values of the decision tree and the random forest method were 0.906 and 0.974, respectively, when serum IgG4 levels were included in the analysis. Excluding serum IgG4 levels, the AUROC curve value of the analysis by the random forest method was 0.925. CONCLUSION: Based on machine learning in a multicenter collaboration, with or without serum IgG4 data, basic patient characteristics and blood test findings alone were sufficient to differentiate IgG4-RD from non-IgG4-RD.

Discovery of natural Miscanthus (Poaceae) triploid plants in sympatric populations of Miscanthus sacchariflorus and Miscanthus sinensis in southern Japan.

PREMISE OF THE STUDY: Looming petroleum shortages and projected negative impacts of human-induced climate change may be partly alleviated by the development and use of bioenergy feedstock crops. Miscanthus ×giganteus, a highly productive sterile triploid hybrid grass that was discovered in Japan several decades ago, has considerable potential as an alternative source of energy. Given the risks, however, involved in the reliance upon production of one clone of this hybrid, which is a natural cross between Miscanthus sacchariflorus and Miscanthus sinensis, for lignocellulosic bioenergy production, natural occurrences of triploidy were investigated in sympatric populations of tetraploid M. sacchariflorus and diploid M. sinensis in Japan. METHODS: Seeds were counted and DNA content was estimated by flow cytometry for plants of M. sacchariflorus and M. sinensis in several sympatric populations throughout Japan. Chromosomes were also counted for select plants. KEY RESULTS: Based on seed-set data, M. sacchariflorus has significantly lower seed set than M. sinensis in Japan. Putative triploid seeds were found on M. sacchariflorus plants in southern Japan. CONCLUSIONS: This is the first report of the natural occurrence of Miscanthus triploid plants in several decades. If found to be sterile and similar in productivity to the commonly cultivated clone of M. ×giganteus, these triploid plants might serve as additional sources of genetic variation for bioenergy production. Seed set data also indicates that other triploid plants might be found in more northern regions of Japan.

Adaptability of Napiergrass (Pennisetum purpureum Schumach.) for Weed Control in Site of Animals Buried after Foot-and-Mouth Disease Infection.

After the infection of foot-and-mouth disease outbreaks in Miyazaki, Japan, in 2010, cattle and swine were slaughtered and buried in a site of 100 ha, where weed control is difficult and costly since lands are unlevelled and prohibited to be plowed for 3 years. To consider the adaptability of napiergrass (Pennisetum purpureum Schumach.) to the animal burial site for weed control, two napiergrass varieties, normal Wruk wona (WK) and dwarf late-heading variety (DL), were transplanted, compared with sowing of maize (MZ) and sorghum (SR) in both burial (BU) and neighboring bordered area (BO) in mid-June 2011. Even though several weed control methods were subjected to lands, MZ and SR failed to be established stably at only 1/3-1/2 due to the suppression of growth by indigenous weeds, while WK and DL successfully established as high as 82-91% and 73-85%, respectively, in 2011. The poor establishment of MZ and SR after sowing tended to be increased with the year from establishment. Plant dry matter yield and cellulose concentration were the highest in WK in 2011, while overwintering ability was constantly higher in DL in the 3 years. It is necessary to consider the utilization of forage plants on the animal burial site.

Soil carbon stocks and carbon sequestration rates in seminatural grassland in Aso region, Kumamoto, Southern Japan.

Global soil carbon (C) stocks account for approximately three times that found in the atmosphere. In the Aso mountain region of Southern Japan, seminatural grasslands have been maintained by annual harvests and/or burning for more than 1000 years. Quantification of soil C stocks and C sequestration rates in Aso mountain ecosystem is needed to make well-informed, land-use decisions to maximize C sinks while minimizing C emissions. Soil cores were collected from six sites within 200 km(2) (767-937 m asl.) from the surface down to the k-Ah layer established 7300 years ago by a volcanic eruption. The biological sources of the C stored in the Aso mountain ecosystem were investigated by combining C content at a number of sampling depths with age (using (14) C dating) and δ(13) C isotopic fractionation. Quantification of plant phytoliths at several depths was used to make basic reconstructions of past vegetation and was linked with C-sequestration rates. The mean total C stock of all six sites was 232 Mg C ha(-1) (28-417 Mg C ha(-1) ), which equates to a soil C sequestration rate of 32 kg C ha(-1)  yr(-1) over 7300 years. Mean soil C sequestration rates over 34, 50 and 100 years were estimated by an equation regressing soil C sequestration rate against soil C accumulation interval, which was modeled to be 618, 483 and 332 kg C ha(-1)  yr(-1) , respectively. Such data allows for a deeper understanding in how much C could be sequestered in Miscanthus grasslands at different time scales. In Aso, tribe Andropogoneae (especially Miscanthus and Schizoachyrium genera) and tribe Paniceae contributed between 64% and 100% of soil C based on δ(13) C abundance. We conclude that the seminatural, C4 -dominated grassland system serves as an important C sink, and worthy of future conservation.

Effects of resource heterogeneity on nitrogen translocation within clonal fragments of Sasa palmata: an isotopic (15N) assessment.

BACKGROUND AND AIMS: Clonal fragments of the rhizomatous dwarf bamboo Sasa palmata, which widely predominates in temperate regions of Japan, were grown under heterogeneous resource conditions such as gap understories or nutrient-patchy grassland. Clonal fragments develop multiple ramets with long rhizomes and appear to be physiologically integrated by the translocation of assimilates. The glasshouse experiment reported here was designed to clarify the mechanisms of physiological integration of nitrogen more precisely. METHODS: To assess how resource conditions influence the amount of nitrogen translocation, and which organ acts as the strongest sink, two experiments were conducted that traced movement of 15N label between interconnected pairs of ramets to compare homogeneous and heterogeneous light and soil nitrogen conditions. KEY RESULTS: The amount of 15N translocated to leaves was between 9% and 11% greater in high-N and high-light ramets in the heterogeneous compared with homogeneous treatments. Under heterogeneous soil nitrogen conditions, translocation increased from individual ramets in resource-rich patches to ramets in resource-poor patches, while the reverse was true under heterogeneous light environments, reflecting differences in the positions of leaves that act as the strongest sinks. Neither the mass increments nor the total mass of clonal fragments was significantly affected by heterogeneity of either light or nutrients, possibly because the experimental period was too short for differences to manifest themselves. CONCLUSIONS: This study clearly demonstrated that nitrogen is readily translocated between ramets, particularly under heterogeneous resource conditions. The translocation patterns were governed by functional 'division of labour' mechanisms that resulted in net nitrogen movement from understory sites to gaps, thereby enhancing the carbon acquisition of the whole fragment. Thus, physiological integration may provide benefits for S. palmata when it is growing under heterogeneous conditions in which there are deficits of certain environmental resources.