Stiffness of primordial germ cells is required for their extravasation in avian embryos

細胞の血行性転移の新たな仕組みを発見 --世界初、新たながん転移抑止戦略の開発にも期待--. 京都大学プレスリリース. 2022-12-13.Unlike mammals, primordial germ cells (PGCs) in avian early embryos exploit blood circulation to translocate to the somatic gonadal primordium, but how circulating PGCs undergo extravasation remains elusive. We demonstrate with single-cell level live-imaging analyses that the PGCs are arrested at a specific site in the capillary plexus, which is predominantly governed by occlusion at a narrow path in the vasculature. The occlusion is enabled by a heightened stiffness of the PGCs mediated by actin polymerization. Following the occlusion, PGCs reset their stiffness to soften in order to squeeze through the endothelial lining as they transmigrate. Our discovery also provides a model for the understanding of metastasizing cancer extravasation occurring mainly by occlusion

Impaired mitochondrial oxidative phosphorylation capacity in epicardial adipose tissue is associated with decreased concentration of adiponectin and severity of coronary atherosclerosis

Epicardial adipose tissue (EAT), a source of adipokines, is metabolically active, but the role of EAT mitochondria in coronary artery disease (CAD) has not been established. We investigated the association between EAT mitochondrial respiratory capacity, adiponectin concentration in the EAT, and coronary atherosclerosis. EAT samples were obtained from 25 patients who underwent elective cardiac surgery. Based on the coronary angiographycal findings, the patients were divided into two groups; coronary artery disease (CAD; n= 14) and non-CAD (n = 11) groups. The mitochondrial respiratory capacities including oxidative phosphorylation (OXPHOS) capacity with non-fatty acid (complex I and complex I + II-linked) substrates and fatty acids in the EAT were significantly lowered in CAD patients. The EAT mitochondrial OXPHOS capacities had a close and inverse correlation with the severity of coronary artery stenosis evaluated by the Gensini score. Intriguingly, the protein level of adiponectin, an anti-atherogenic adipokine, in the EAT was significantly reduced in CAD patients, and it was positively correlated with the mitochondrial OXPHOS capacities in the EAT and inversely correlated with the Gensini score. Our study showed that impaired mitochondrial OXPHOS capacity in the EAT was closely linked to decreased concentration of adiponectin in the EAT and severity of coronary atherosclerosis

Effects of Three Types of Organic Fertilizers on Greenhouse Gas Emissions in a Grassland on Andosol in Southern Hokkaido, Japan

Reduction of chemical fertilizers and effective use of livestock excrement are required for the realization of sustainable agriculture and reduction of greenhouse gas (GHG) emissions. The purpose of this study was to estimate the reduction rate of GHG emissions represented by comparing global warming potential (GWP) using organic fertilizers instead of chemical fertilizers. The study was conducted in a managed grassland on Andosol in southern Hokkaido for 3 years from May 2017 to April 2020. There were five treatment plots: no fertilizer, chemical fertilizer, manure, slurry, and digestive fluid. Organic fertilizers were applied such that the amount of NPK did not exceed the recommended application rate, and the shortage was supplemented with chemical fertilizers. Fluxes in CO2 caused by heterotrophic respiration (RH), CH4, and N2O were measured using the closed chamber method. Net ecosystem carbon balance (NECB) was obtained as net primary production + organic fertilizer application-RH-harvest. The GWP was estimated by CO2 equivalent NECB and CH4 and N2O emissions in each treatment. Chemical fertilizer nitrogen application rates in the organic fertilizer treatments were reduced by 10% for manure, 19.7% for slurry and 29.7% for digestive fluid compared to chemical fertilizer only, but the grass yields were not significantly different among the fertilizer treatments. The 3-year NECB showed significantly smallest carbon loss in manure treatment, and smaller carbon loss in the organic fertilizer treatments than in the chemical fertilizer only. The reduction rate in the GWP with use of organic fertilizers relative to that of chemical fertilizer was 16.5% for slurry, 27.0% for digestive fluid, and 36.2% for manure. The NECB accounted for more than 90% of the GWP in all treatments. CH4 emissions were chemical fertilizer only > digestive fluid > manure. As a conclusion, these organic fertilizers can be used without no reduction of crop yield instead of chemical fertilizer, however, manure is the best way to increase soil carbon and to decrease GWP, followed by digestive fluid

Remission of Psychosis in Treatment-Resistant Schizophrenia following Bone Marrow Transplantation: A Case Report

The authors present the case of a 24-year-old male with treatment-resistant schizophrenia, with predominant severe delusion and hallucination, who received bone marrow transplantation (BMT) for acute myeloid leukemia. After BMT, he showed a remarkable reduction in psychotic symptoms without administration of neuroleptics. He also showed drastic improvement in social functioning. Follow-up evaluations 2 and 4 years after BMT showed persistent significant improvement of the psychotic state and social functioning. Recent findings show that the major underlying pathogenic mechanism of schizophrenia is immune dysregulation. Thus, conceptually, BMT, a cellular therapy, that facilitates the counteractive processes of balancing inflammation by immune regulation, could produce beneficial clinical effects in patients with treatment-resistant schizophrenia. Further studies are required to define the true benefits of BMT for the possible curative treatment of schizophrenia

Impact of High Respiratory Exchange Ratio During Submaximal Exercise on Adverse Clinical Outcome in Heart Failure

Background: Oxygen uptake (V̇O2) at peak workload and anaerobic threshold (AT) workload are often used for grading heart failure (HF) severity and predicting all-cause mortality. The clinical relevance of respiratory exchange ratio (RER) during exercise, however, is unknown.Methods and Results: We retrospectively studied 295 HF patients (57±15 years, NYHA class I–III) who underwent cardiopulmonary exercise testing. RER was measured at rest; at AT workload; and at peak workload. Peak V̇O2 had an inverse correlation with RER at AT workload (r=−0.256), but not at rest (r=−0.084) or at peak workload (r=0.090). Using median RER at AT workload, we divided the patients into high RER (≥0.97) and low RER (<0.97) groups. Patients with high RER at AT workload were characterized by older age, lower body mass index, anemia, and advanced NYHA class. After propensity score matching, peak V̇O2 tended to be lower in the high-RER than in the low-RER group (14.9±4.5 vs. 16.1±5.0 mL/kg/min, P=0.06). On Kaplan-Meier analysis, HF patients with a high RER at AT workload had significantly worse clinical outcomes, including all-cause mortality and rate of readmission due to HF worsening over 3 years (29% vs. 15%, P=0.01). Conclusions: High RER during submaximal exercise, particularly at AT workload, is associated with poor clinical outcome in HF patients