33 research outputs found
Influence of the Difference in the Size of Cobalt-60 Souce (Wafer Type and Pallet Type) on the Spatial Dose Distribution of Moving Therapy
Identification of 45 New Neutron-Rich Isotopes Produced by In-Flight Fission of a 238U Beam at 345 MeV/nucleon
A search for new isotopes using in-flight fission of a 345 MeV/nucleon 238U
beam has been carried out at the RI Beam Factory at the RIKEN Nishina Center.
Fission fragments were analyzed and identified by using the superconducting
in-flight separator BigRIPS. We observed 45 new neutron-rich isotopes: 71Mn,
73,74Fe, 76Co, 79Ni, 81,82Cu, 84,85Zn, 87Ga, 90Ge, 95Se, 98Br, 101Kr, 103Rb,
106,107Sr, 108,109Y, 111,112Zr, 114,115Nb, 115,116,117Mo, 119,120Tc,
121,122,123,124Ru, 123,124,125,126Rh, 127,128Pd, 133Cd, 138Sn, 140Sb, 143Te,
145I, 148Xe, and 152Ba
Brown adipose tissue dysfunction promotes heart failure via a trimethylamine N-oxide-dependent mechanism.
Low body temperature predicts a poor outcome in patients with heart failure, but the underlying pathological mechanisms and implications are largely unknown. Brown adipose tissue (BAT) was initially characterised as a thermogenic organ, and recent studies have suggested it plays a crucial role in maintaining systemic metabolic health. While these reports suggest a potential link between BAT and heart failure, the potential role of BAT dysfunction in heart failure has not been investigated. Here, we demonstrate that alteration of BAT function contributes to development of heart failure through disorientation in choline metabolism. Thoracic aortic constriction (TAC) or myocardial infarction (MI) reduced the thermogenic capacity of BAT in mice, leading to significant reduction of body temperature with cold exposure. BAT became hypoxic with TAC or MI, and hypoxic stress induced apoptosis of brown adipocytes. Enhancement of BAT function improved thermogenesis and cardiac function in TAC mice. Conversely, systolic function was impaired in a mouse model of genetic BAT dysfunction, in association with a low survival rate after TAC. Metabolomic analysis showed that reduced BAT thermogenesis was associated with elevation of plasma trimethylamine N-oxide (TMAO) levels. Administration of TMAO to mice led to significant reduction of phosphocreatine and ATP levels in cardiac tissue via suppression of mitochondrial complex IV activity. Genetic or pharmacological inhibition of flavin-containing monooxygenase reduced the plasma TMAO level in mice, and improved cardiac dysfunction in animals with left ventricular pressure overload. In patients with dilated cardiomyopathy, body temperature was low along with elevation of plasma choline and TMAO levels. These results suggest that maintenance of BAT homeostasis and reducing TMAO production could be potential next-generation therapies for heart failure.We thank Kaori Yoshida, Keiko Uchiyama, Satomi Kawai, Naomi Hatanaka, Yoko Sawaguchi, Runa Washio,
Takako Ichihashi, Nanako Koike, Keiko Uchiyama, Masaaki Nameta (Niigata University), Kaori Igarashi, Kaori
Saitoh, Keiko Endo, Hiroko Maki, Ayano Ueno, Maki Ohishi, Sanae Yamanaka, Noriko Kagata (Keio University)
for their excellent technical assistance, C. Ronald Kahn (Joslin Diabetes Center and Harvard Medical School)
for providing the BAT cell line, Evan Rosen (Harvard Medical School) for providing us Ucp-Cre mice, Kosuke
Morikawa (Kyoto University), Tomitake Tsukihara (University of Hyogo) and Shinya Yoshikawa (University of
Hyogo) for their professional opinions and suggestions. Tis work was supported by a Grant-in-Aid for Scientifc Research (A) (20H00533) from MEXT, AMED under Grant Numbers JP20ek0210114, and AMED-CREST
under Grant Number JP20gm1110012, and Moonshot Research and Development Program (21zf0127003s0201),
MEXT Supported Program for the Strategic Research Foundation at Private Universities Japan, Private University
Research Branding Project, and Leading Initiative for Excellent Young Researchers, and grants from the Takeda
Medical Research Foundation, the Vehicle Racing Commemorative Foundation, Ono Medical Research Foundation, and the Suzuken Memorial Foundation (to T.M.). Support was also provided by a Grants-in-Aid for Young
Scientists (Start-up) (26893080), and grants from the Uehara Memorial Foundation, Kowa Life Science Foundation, Manpei Suzuki Diabetes Foundation, SENSHIN Medical Research Foundation, ONO Medical Research
Foundation, Tsukada Grant for Niigata University Medical Research, Te Nakajima Foundation, SUZUKEN
memorial foundation, HOKUTO Corporation, Mochida Memorial Foundation for Medical & Pharmaceutical
Research, Grants-in-Aid for Encouragement of Young Scientists (A) (16H06244), Daiichi Sankyo Foundation of
Life Science, AMED Project for Elucidating and Controlling Mechanisms of Aging and Longevity under Grant
Number JP17gm5010002, JP18gm5010002, JP19gm5010002, JP20gm5010002, JP21gm5010002, Astellas Foundation for Research on Metabolic Disorders, Research grant from Naito Foundation, Te Japan Geriatrics Society
(to I.S.); by a Grant-in-Aid for Scientifc Research (C) (19K08974), Yujin Memorial Grant, Sakakibara Memorial
Research Grant from Te Japan Research Promotion Society for Cardiovascular Diseases, TERUMO Life Science Foundation, Kanae Foundation (to Y.Y.), JST ERATO (JPMJER1902), AMED-CREST (JP20gm1010009),
the Takeda Science Foundation, the Food Science Institute Foundation (to S.F.), and by a grant from Bourbon
(to T.M., I.S. and Y.Y.).S