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Florigen, the mobile signal that moves from an induced leaf to the shoot apex and causes flowering, has eluded identification since it was first proposed 70 years ago. Understanding the nature of the mobile flowering signal would provide a key insight into the molecular mechanism of floral induction. Recent studies suggest that the Arabidopsis FLOWERING LOCUS T (FT) gene is a candidate for encoding florigen. We show that the protein encoded by Hd3a, a rice ortholog of FT, moves from the leaf to the shoot apical meristem and induces flowering in rice. These results suggest that the Hd3a protein may be the rice florigen.

Objective: A formula is needed that is practical for current livestock breeding methods and that predicts the approximate rate of inbreeding (∆F) in populations where selection is performed according to four-path programs (sires to breed sons, sires to breed daughters, dams to breed sons, and dams to breed daughters). The formula widely used to predict inbreeding neglects selection, we need to develop a new formula that can be applied with or without selection.Methods: The core of the prediction is to incorporate the long-tern genetic influence of the selected parents in four-selection paths executed as sires to breed sons, sires to breed daughters, dams to breed sons, and dams to breed daughters. The rate of inbreeding was computed as the magnitude that is proportional to the sum of squared long-term genetic contributions of the parents of four-selection paths to the selected offspring.Results: We developed a formula to predict the rate of inbreeding in populations undergoing four-path selection on genomically enhanced breeding values and with discrete generations. The new formula can be applied with or without selection. Neglecting the effects of selection led to underestimation of the rate of inbreeding by 40% to 45%.Conclusion: The formula we developed here would be highly useful as a practical method for predicting the approximate rate of inbreeding (ΔF) in populations where selection is performed according to four-path programs.

Objective: A formula is needed that is practical for current livestock breeding methods and that predicts the approximate rate of inbreeding (ΔF) in populations where selection is performed according to four-path programs (sires to breed sons, sires to breed daughters, dams to breed sons, and dams to breed daughters). The formula widely used to predict inbreeding neglects selection, we need to develop a new formula that can be applied with or without selection. Methods: The core of the prediction is to incorporate the long-tern genetic influence of the selected parents in four-selection paths executed as sires to breed sons, sires to breed daughters, dams to breed sons, and dams to breed daughters. The rate of inbreeding was computed as the magnitude that is proportional to the sum of squared long-term genetic contributions of the parents of four-selection paths to the selected offspring. Results: We developed a formula to predict the rate of inbreeding in populations undergoing four-path selection on genomically enhanced breeding values and with discrete generations. The new formula can be applied with or without selection. Neglecting the effects of selection led to underestimation of the rate of inbreeding by 40% to 45%. Conclusion: The formula we developed here would be highly useful as a practical method for predicting the approximate rate of inbreeding (ΔF) in populations where selection is performed according to four-path programs.

Chronic kidney disease is an important concern in preventive medicine, but the rate of decline in renal function in healthy population is not well defined. The purpose of this study was to determine reference values for the estimated glomerular filtration rate (eGFR) and rate of decline of eGFR in healthy subjects and to evaluate factors associated with this decline using a large cohort in Japan. Retrospective cross-sectional and longitudinal studies were performed with healthy subjects aged ≥18 years old who received a medical checkup. Reference values for eGFR were obtained using a nonparametric method and those for decline of eGFR were calculated by mixed model analysis. Relationships of eGFR decline rate with baseline variables were examined using a linear least-squares method. In the cross-sectional study, reference values for eGFR were obtained by gender and age in 72,521 healthy subjects. The mean (±SD) eGFR was 83.7±14.7 ml/min/1.73 m2. In the longitudinal study, reference values for eGFR decline rate were obtained by gender, age, and renal stage in 45,586 healthy subjects. In the same renal stage, there was little difference in the rate of decline regardless of age. The decline in eGFR depended on the renal stage and was strongly related to baseline eGFR, with a faster decline with a higher baseline eGFR and a slower decline with a lower baseline eGFR. The mean (±SD) eGFR decline rate was ‒1.07±0.42 ml/min/1.73 m2/year (‒1.29±0.41%/year) in subjects with a mean eGFR of 81.5±11.6 ml/min/1.73 m2. The present study clarified for the first time the reference values for the rate of eGFR decline stratified by gender, age, and renal stage in healthy subjects. The rate of eGFR decline depended mainly on baseline eGFR, but not on age, with a slower decline with a lower baseline eGFR.

Presepsin is highlighted as a diagnostic and prognostic marker of sepsis. Little information is available regarding the accurate association between presepsin levels and the degree of kidney function. We analyzed presepsin levels in patients with a glomerular filtration rate (GFR) in the categories G1 to G5, evaluated via inulin renal clearance test, and receiving hemodialysis (HD). Patients who were not receiving HD were included if they had undergone inulin renal clearance measurements for the accurate measurement of GFR (measured GFR), and patients who were receiving hemodialysis (HD) were included if they had anuria. Exclusion criteria were infection, cancer, liver disease, autoimmune disorders, or steroid or immunosuppressant use. GFR category was defined as follows; G1: GFR ≥ 90 ml/min/1.73 m2, G2: GFR = 60 to 90 ml/min/1.73 m2, G3: GFR = 30 to 60 ml/min/1.73 m2, G4: GFR = 15 to 30 ml/min/1.73 m2, G5: GFR ≤ 15 ml/min/1.73 m2. Seventy-one patients were included. The median (IQR) presepsin values of patients in each GFR category were as follows: G1 + G2: 69.8 (60.8-85.9) pg/ml; G3: 107.0 (68.7-150.0) pg/ml; G4: 171.0 (117.0-200.0) pg/ml; G5: 251.0 (213.0-297.5) pg/ml; and HD: 1160.0 (1070.0-1400.0) pg/ml. The log-transformed presepsin values, excluding patients receiving HD, inversely correlated with the measured GFR (Pearson's correlation coefficient = -0.687, P < 0.001). The multivariate analysis revealed that measured GFR and hemoglobin levels significantly correlated with elevated presepsin levels. Presepsin levels were markedly high in patients receiving HD, similar to values seen in patients with severe sepsis or septic shock. In patients who were not receiving HD, presepsin levels increased as GFR decreased. Thus, the evaluation of presepsin levels in patients with chronic kidney disease requires further consideration, and a different cutoff value is needed for diagnosing sepsis in such patients.

Epithelial ovarian cancer (EOC) is widely recognized as the most lethal gynecological malignancy; however, its early-stage detection remains a considerable clinical challenge. To address this, we have introduced a new method, named Comprehensive Serum Glycopeptide Spectral Analysis (CSGSA), which detects early-stage cancer by combining glycan alterations in serum glycoproteins with tumor markers. We detected 1712 glycopeptides using liquid chromatography–mass spectrometry from the sera obtained from 564 patients with EOC and 1149 controls across 13 institutions. Furthermore, we used a convolutional neural network to analyze the expression patterns of the glycopeptides and tumor markers. Using this approach, we successfully differentiated early-stage EOC (Stage I) from non-EOC, with an area under the curve (AUC) of 0.924 in receiver operating characteristic (ROC) analysis. This method markedly outperforms conventional tumor markers, including cancer antigen 125 (CA125, 0.842) and human epididymis protein 4 (HE4, 0.717). Notably, our method exhibited remarkable efficacy in differentiating early-stage ovarian clear cell carcinoma from endometrioma, achieving a ROC-AUC of 0.808, outperforming CA125 (0.538) and HE4 (0.557). Our study presents a promising breakthrough in the early detection of EOC through the innovative CSGSA method. The integration of glycan alterations with cancer-related tumor markers has demonstrated exceptional diagnostic potential.

A bstract We derive an infinite set of recursion formulae for Nekrasov instanton partition function for linear quiver U( N ) supersymmetric gauge theories in 4D. They have the structure of a deformed version of algebra which is called SH c algebra (or degenerate double affine Hecke algebra) in the literature. The algebra contains W N algebra with general central charge defined by a parameter β , which gives the Ω background in Nekrasov’s analysis. Some parts of the formulae are identified with the conformal Ward identity for the conformal block function of Toda field theory.

Among antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV), granulomatosis with polyangiitis (GPA) and proteinase 3-ANCA-positive AAV (PR3-AAV) are prevalent in European populations, while microscopic polyangiitis (MPA) and myeloperoxidase-ANCA-positive AAV (MPO-AAV) are predominant in the Japanese. We previously demonstrated association of DRB1*09:01-DQB1*03:03 haplotype, a haplotype common in East Asians but rare in the European populations, with MPA/MPO-AAV, suggesting that a population difference in HLA-class II plays a role in the epidemiology of this disease. To gain further insights, we increased the sample size and performed an extended association study of DRB1 and DPB1 with AAV subsets in 468 Japanese patients with AAV classified according to the European Medicines Agency algorithm (MPA: 285, GPA: 92, eosinophilic GPA [EGPA]: 56, unclassifiable: 35) and 596 healthy controls. Among these patients, 377 were positive for MPO-ANCA and 62 for PR3-ANCA. The significance level was set at α = 3.3x10-4 by applying Bonferroni correction. The association of DRB1*09:01 with MPO-AAV was confirmed (allele model, P = 2.1x10-4, odds ratio [OR] = 1.57). Protective association of DRB1*13:02 was detected against MPO-AAV (allele model, P = 2.3x10-5, OR = 0.42) and MPA (dominant model, P = 2.7x10-4, OR = 0.43). A trend toward increased frequency of DPB1*04:01, the risk allele for GPA in European populations, was observed among Japanese patients with PR3-AAV when conditioned on DRB1*13:02 (Padjusted = 0.0021, ORadjusted = 3.48). In contrast, the frequency of DPB1*04:01 was decreased among Japanese patients with MPO-AAV, and this effect lost significance when conditioned on DRB1*13:02 (Padjusted = 0.16), suggesting that DRB1*13:02 or other allele(s) in linkage disequilibrium may be responsible for the protection. The differential association of DPB1*04:01 with PR3-AAV and MPO-AAV and difference in DPB1*04:01 allele frequencies between populations supported the hypothesis that the HLA-class II population difference may account in part for these epidemiologic characteristics. Furthermore, taken together with our previous observations, the haplotype carrying DRB1*13:02 was suggested to be a shared protective factor against multiple autoimmune diseases.

Background We previously estimated the prevalence of chronic kidney disease (CKD) stages 3–5 at 19.1 million based on data from the Japanese annual health check program for 2000–2004 using the Modification of Diet in Renal Disease (MDRD) equation multiplied by the coefficient 0.881 for the Japanese population. However, this equation underestimates the GFR, particularly for glomerular filtration rates (GFRs) of over 60 ml/min/1.73 m 2 . We did not classify the participants as CKD stages 1 and 2 because we did not obtain proteinuria data for all of the participants. We re-estimated the prevalence of CKD by measuring proteinuria using a dipstick test and by calculating the GFR using a new equation that estimates GFR based on data from the Japanese annual health check program in 2005. Methods Data were obtained for 574,024 (male 240,594, female 333,430) participants over 20 years old taken from the general adult population, who were from 11 different prefectures in Japan (Hokkaido, Yamagata, Fukushima, Tochigi, Ibaraki, Tokyo, Kanazawa, Osaka, Fukuoka, Miyazaki and Okinawa) and took part in the annual health check program in 2005. The glomerular filtration rate (GFR) of each participant was computed from the serum creatinine value using a new equation: GFR (ml/min/1.73 m 2 ) = 194 × Age −0.287  × S-Cr −1.094  (if female × 0.739). The CKD population nationwide was calculated using census data from 2005. We also recalculated the prevalence of CKD in Japan assuming that the age composition of the population was same as that in the USA. Results The prevalence of CKD stages 1, 2, 3, and 4 + 5 were 0.6, 1.7, 10.4 and 0.2% in the study population, which resulted in predictions of 0.6, 1.7, 10.7 and 0.2 million patients, respectively, nationwide. The prevalence of low GFR was significantly higher in the hypertensive and proteinuric populations than it was in the populations without proteinuria or hypertension. The prevalence rate of CKD in Japan was similar to that in the USA when the Japanese general population was age adjusted to the US 2005 population estimate. Conclusion About 13% of the Japanese adult population—approximately 13.3 million people—were predicted to have CKD in 2005.

Background Membranous nephropathy (MN) is the leading cause of nephrotic syndrome in adults. Anti-M-type phospholipase A2 receptor (anti-PLA2R) antibodies are found in most patients with idiopathic MN (iMN) worldwide, but the prevalence of anti-PLA2R antibodies among Japanese patients with MN is unknown. In this study, we determined the prevalence of anti-PLA2R antibodies in Japanese patients with MN. Methods The study population of our retrospective cross-sectional consisted of 131 patients with biopsy-proven MN who had not received any immunosuppressive treatments at time of both renal biopsy and serum sample collection. Of these, 100 had iMN and 31 had secondary MN (sMN). The circulating anti-PLA2R antibodies were analyzed using a highly sensitive Western blot analysis. Analysis was performed under non-reducing conditions with a human glomerular extract at serum dilutions of 1:25, 1:10, and 1 as the primary antibody. Results Anti-PLA2R antibodies were detected in 53 (53 %) of 100 patients with iMN and 0 (0 %) of 31 patients with sMN. The prevalence of anti-PLA2R antibodies was higher in patients with nephrotic syndrome (61 %) than in patients without nephrotic syndrome (43 %). The number of patients with serum albumin ≤3.0 g/dL was significantly higher in those with anti-PLA2R antibodies (92 %) than that in those without them (68 %). Conclusions Anti-PLA2R antibodies were found in Japanese patients with iMN; however, the prevalence was lower than that of any other Asian country. This may indicate that the presence of other pathogenic antigens plays a significant role in Japanese patients with iMN.