Identification of stem cells during prepubertal spermatogenesis via monitoring of nucleostemin promoter activity

Division of Molecular Genetic

Near-wall rheotaxis of the ciliate Tetrahymena induced by the kinesthetic sensing of cilia

泳ぐ微生物が海まで流されない理由 --SDGsに欠かせない小さな生物たちの振る舞いを解明--. 京都大学プレスリリース. 2021-10-21.To survive in harsh environments, single-celled microorganisms autonomously respond to external stimuli, such as light, heat, and flow. Here, we elucidate the flow response of Tetrahymena, a well-known single-celled freshwater microorganism. Tetrahymena moves upstream against an external flow via a behavior called rheotaxis. While micrometer-sized particles are swept away downstream in a viscous flow, what dynamics underlie the rheotaxis of the ciliate? Our experiments reveal that Tetrahymena slides along walls during upstream movement, which indicates that the cells receive rotational torque from shear flow to control cell orientation. To evaluate the effects of the shear torque and propelling speed, we perform a numerical simulation with a hydrodynamic model swimmer adopting cilia dynamics in a shear flow. The swimmer orientations converge to an upstream alignment, and the swimmer slides upstream along a boundary wall. The results suggest that Tetrahymena automatically responds to shear flow by performing rheotaxis using cilia-stalling mechanics

Development of pericardial fat count images using a combination of three different deep-learning models

Rationale and Objectives: Pericardial fat (PF), the thoracic visceral fat surrounding the heart, promotes the development of coronary artery disease by inducing inflammation of the coronary arteries. For evaluating PF, this study aimed to generate pericardial fat count images (PFCIs) from chest radiographs (CXRs) using a dedicated deep-learning model. Materials and Methods: The data of 269 consecutive patients who underwent coronary computed tomography (CT) were reviewed. Patients with metal implants, pleural effusion, history of thoracic surgery, or that of malignancy were excluded. Thus, the data of 191 patients were used. PFCIs were generated from the projection of three-dimensional CT images, where fat accumulation was represented by a high pixel value. Three different deep-learning models, including CycleGAN, were combined in the proposed method to generate PFCIs from CXRs. A single CycleGAN-based model was used to generate PFCIs from CXRs for comparison with the proposed method. To evaluate the image quality of the generated PFCIs, structural similarity index measure (SSIM), mean squared error (MSE), and mean absolute error (MAE) of (i) the PFCI generated using the proposed method and (ii) the PFCI generated using the single model were compared. Results: The mean SSIM, MSE, and MAE were as follows: 0.856, 0.0128, and 0.0357, respectively, for the proposed model; and 0.762, 0.0198, and 0.0504, respectively, for the single CycleGAN-based model. Conclusion: PFCIs generated from CXRs with the proposed model showed better performance than those with the single model. PFCI evaluation without CT may be possible with the proposed method

Identification of a tomato UDP-arabinosyltransferase for airborne volatile reception

植物間コミュニケーションの仕組みを解明 --受容した香りを防御物質に変える遺伝子発見--. 京都大学プレスリリース. 2023-02-28.Volatiles from herbivore-infested plants function as a chemical warning of future herbivory for neighboring plants. (Z)-3-Hexenol emitted from tomato plants infested by common cutworms is taken up by uninfested plants and converted to (Z)-3-hexenyl β-vicianoside (HexVic). Here we show that a wild tomato species (Solanum pennellii) shows limited HexVic accumulation compared to a domesticated tomato species (Solanum lycopersicum) after (Z)-3-hexenol exposure. Common cutworms grow better on an introgression line containing an S. pennellii chromosome 11 segment that impairs HexVic accumulation, suggesting that (Z)-3-hexenol diglycosylation is involved in the defense of tomato against herbivory. We finally reveal that HexVic accumulation is genetically associated with a uridine diphosphate-glycosyltransferase (UGT) gene cluster that harbors UGT91R1 on chromosome 11. Biochemical and transgenic analyses of UGT91R1 show that it preferentially catalyzes (Z)-3-hexenyl β-D-glucopyranoside arabinosylation to produce HexVic in planta

A Genome-Wide Association Study Identified AFF1 as a Susceptibility Locus for Systemic Lupus Eyrthematosus in Japanese

Systemic lupus erythematosus (SLE) is an autoimmune disease that causes multiple organ damage. Although recent genome-wide association studies (GWAS) have contributed to discovery of SLE susceptibility genes, few studies has been performed in Asian populations. Here, we report a GWAS for SLE examining 891 SLE cases and 3,384 controls and multi-stage replication studies examining 1,387 SLE cases and 28,564 controls in Japanese subjects. Considering that expression quantitative trait loci (eQTLs) have been implicated in genetic risks for autoimmune diseases, we integrated an eQTL study into the results of the GWAS. We observed enrichments of cis-eQTL positive loci among the known SLE susceptibility loci (30.8%) compared to the genome-wide SNPs (6.9%). In addition, we identified a novel association of a variant in the AF4/FMR2 family, member 1 (AFF1) gene at 4q21 with SLE susceptibility (rs340630; P = 8.3×10−9, odds ratio = 1.21). The risk A allele of rs340630 demonstrated a cis-eQTL effect on the AFF1 transcript with enhanced expression levels (P<0.05). As AFF1 transcripts were prominently expressed in CD4+ and CD19+ peripheral blood lymphocytes, up-regulation of AFF1 may cause the abnormality in these lymphocytes, leading to disease onset

Genetics of rheumatoid arthritis contributes to biology and drug discovery

A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological datasets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA)1. Here, we performed a genome-wide association study (GWAS) meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating ~10 million single nucleotide polymorphisms (SNPs). We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 1012–4. We devised an in-silico pipeline using established bioinformatics methods based on functional annotation5, cis-acting expression quantitative trait loci (cis-eQTL)6, and pathway analyses7–9 – as well as novel methods based on genetic overlap with human primary immunodeficiency (PID), hematological cancer somatic mutations and knock-out mouse phenotypes – to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery

Natural Killer T Cells Are Involved in Adipose Tissues Inflammation and Glucose Intolerance in Diet-Induced Obese Mice

Objective: Macrophage as well as lymphocyte infiltration in adipose tissue may contribute to the pathogenesis of obesity-mediated metabolic disorders. Natural killer T (NKT) cells, which integrate proinflammatory cytokines, have been demonstrated in the atherosclerotic lesions and also in visceral adipose tissue. We thus determined whether NKT cells are involved in glucose intolerance and adipose tissue inflammation in diet-induced obese mice. Methods and Results: To determine whether NKT cells are involved in the development of glucose intolerance, male β2 microglobulin knockout mice lacking NKT cells (KO) and C57BL/6J (WT) mice were fed with a high fat diet (HFD) for 13 weeks. Body weight and visceral obesity were comparable between WT and KO mice. However, macrophage infiltration was reduced in adipose tissue and glucose intolerance was significantly ameliorated in KO mice. To further confirm that NKT cells are involved in these abnormalities, α-galactosylceramide (αGC, 0.1μg/g body weight), which specifically activates NKT cells, were administered after 13 weeks of HFD feeding. αGC significantly exacerbated glucose intolerance and also macrophage infiltration as well as cytokine gene expression in adipose tissue. Conclusions: NKT cells play a crucial role in the development of adipose tissue inflammation and glucose intolerance in diet-induced obesity

Intracorporeal hemi-hand-sewn technique for Billroth-I gastroduodenostomy after laparoscopic distal gastrectomy: comparative analysis with laparoscopy-assisted distal gastrectomy

Aim: The purpose of this study was to evaluate the clinical feasibility and efficacy of the intracorporeal hemi-hand-sewn (IC-HHS) technique for Billroth-I gastroduodenostomy in comparison with extracorporeal total hand-sewn (EC-THS) anastomosis. We also examined the size of resected specimens in each procedure.Methods: The number of enrolled cases of EC-THS and IC-HHS anastomosis groups were 85 and 110 cases, respectively. Perioperative data and the measured sizes of resected specimens were analyzed.Results: Operation time in the IC-HHS group was significantly longer than the EC-THS group (234.8 min vs. 275.0 min, P &lt; 0.01), whereas intraoperative blood loss was less in the IC-HHS group (48.4 mL vs. 25.4 mL, P = 0.03). There were no procedure-related complications in the IC-HHS group. The greater curvature of the EC-THS group was significantly shorter than the IC-HHS group (214.6 mm vs. 228.7 mm, P &lt; 0.01). There was no correlation between body mass index (BMI) and the length of the greater curvature in the IC-HHS group (r = 0.07, P = 0.47), but in the EC-THS group, the length of the greater curvature tends to shorten as BMI increases (r = -0.45, P &lt; 0.01).Conclusion: IC-HHS technique for Billroth-I gastroduodenostomy revealed feasible with acceptable operation time and postoperative outcome. Another advantage of total laparoscopic distal gastrectomy that intracorporeal transection can facilitate is to ensure an adequate proximal margin, especially in obese middle gastric cancer patients