Boron Arylations of Subporphyrins with Aryl Zinc Reagents

Boron arylations of B‐(methoxo)triphenylsubporphyrin have been developed with a combined use of ArZnI⋅LiCl and trimethylsilyl chloride. Aryl zinc reagents bearing bromo, cyano, amide, and ester groups can be employed for the B‐arylation reaction to provide the corresponding B‐arylated subporphyrins in moderate yields. Postmodifications of B‐arylated subporphyrins have been demonstrated without loss of the B−C bond. These modifications include conversion of the cyano group into a benzoyl group with PhMgBr, hydrolysis of the ester group to give B‐(4‐carboxyphenyl)subporphyrin, and Pd‐catalyzed Suzuki–Miyaura coupling of the 4‐bromophenyl group to give a 1,4‐phenylene‐bridged subporphyrin–ZnII porphyrin hybrid that displays intramolecular excitation energy transfer from the subporphyrin to the porphyrin. The newly synthesized B‐arylated subporphyrins have been fully characterized by NMR, UV/Vis absorption and fluorescence spectroscopies, mass spectrometry, electrochemical measurements, and X‐ray diffraction analysis.Bonding B to C: Boron arylations of B‐(methoxo)triphenylsubporphyrin have been developed with a combined use of ArZnI⋅LiCl and trimethylsilyl chloride (TMSCl; see scheme), which allow the synthesis of B‐aryl subporphyrins bearing bromo, cyano, amide, and ester groups. Postmodifications of the B‐aryl subporphyrins have been demonstrated without loss of the B−C bond. Newly synthesized B‐arylated subporphyrins have been fully characterized.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137618/1/chem201504719.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137618/2/chem201504719-sup-0001-misc_information.pd

Measurement of AGN dust extinction based on the near-infrared flux variability of WISE data

We present the measurement of the line-of-sight extinction of the dusty torus for a large number of obscured active galactic nuclei (AGNs) based on the reddening of the colour of the variable flux component in near-infrared (NIR) wavelengths. We collected long-term monitoring data by $\textit{Wide-field Infrared Survey Explorer (WISE)}$ for 513 local AGNs catalogued by the $\mathit{Swift/}$BAT AGN Spectroscopic Survey (BASS) and found that the multi-epoch NIR flux data in two different bands (WISE $W1$ and $W2$) are tightly correlated for more than 90% of the targets. The flux variation gradient (FVG) in the $W1$ and $W2$ bands was derived by applying linear regression analysis, and we reported that those for unobscured AGNs fall in a relatively narrow range, whereas those for obscured AGNs are distributed in a redder and broader range. The AGN's line-of-sight dust extinction ($A_V$) is calculated using the amount of the reddening in the FVG and is compared with the neutral hydrogen column density ($N_{\rm{}H}$) of the BASS catalogue. We found that the $N_{\rm{}H}/A_V$ ratios of obscured AGNs are greater than those of the Galactic diffuse interstellar medium (ISM) and are distributed with a large scatter by at most two orders of magnitude. Furthermore, we found that the lower envelope of the $N_{\rm{}H}/A_V$ of obscured AGNs is comparable to the Galactic diffuse ISM. These properties of the $N_{\rm{}H}/A_V$ can be explained by increase in the $N_{\rm{}H}$ attributed to the dust-free gas clouds covering the line of sight in the broad-line region.Comment: 11 pages, 7 figures, published in MNRA

Effect of transition metal oxide cocatalyst on the photocatalytic activity of Ag loaded CaTiO₃ for CO₂ reduction with water and water splitting

Various dual cocatalysts consisting of Ag and transition metal oxide (TMOx) were loaded on a CaTiO₃ (CTO) photocatalyst by different loading methods and examined for the photocatalytic CO₂ reduction with water as an electron donor. Compared to the results provided with the single Ag cocatalyst, the dual cocatalyst loaded CTO photocatalyst exhibited a similar or less CO evolution rate and higher H₂ production, meaning that these photocatalyst showed photocatalytic activity for both CO₂ reduction and water splitting. Dual cocatalysts of Ag and TMOx loaded by a photodeposition gave higher CO production rate than those loaded by an impregnation method. The CTO photocatalysts with a single TMOx cocatalyst showed higher activities in both H₂ evolution and O₂ evolution test than the bare CTO and dual cocatalyst loaded CTO photocatalysts, indicating that the photocatalytic activity for water splitting is suppressed by the Ag cocatalyst but improved by the TMOx

22q11欠失症候群モデルマウスの神経発達障害には、マイクロRNAが介在するCxcr4/Cxcl12シグナリングの欠損が寄与する

22q11 deletion syndrome (22q11DS) frequently accompanies psychiatric conditions, some of which are classified as schizophrenia and bipolar disorder in the current diagnostic categorization. However, it remains elusive how the chromosomal microdeletion leads to the mental manifestation at the mechanistic level. Here we show that a 22q11DS mouse model with a deletion of 18 orthologous genes of human 22q11 (Df1/+ mice) has deficits in migration of cortical interneurons and hippocampal dentate precursor cells. Furthermore, Df1/+ mice show functional defects in Chemokine receptor 4/Chemokine ligand 12 (Cxcr4/Cxcl12; Sdf1) signaling, which reportedly underlie interneuron migration. Notably, the defects in interneuron progenitors are rescued by ectopic expression of Dgcr8, one of the genes in 22q11 microdeletion. Furthermore, heterozygous knockout mice for Dgcr8 show similar neurodevelopmental abnormalities as Df1/+ mice. Thus, Dgcr8-mediated regulation of microRNA is likely to underlie Cxcr4/Cxcl12 signaling and associated neurodevelopmental defects. Finally, we observe that expression of CXCL12 is decreased in olfactory neurons from sporadic cases with schizophrenia compared with normal controls. Given the increased risk of 22q11DS in schizophrenia that frequently shows interneuron abnormalities, the overall study suggests that CXCR4/CXCL12 signaling may represent a common downstream mediator in the pathophysiology of schizophrenia and related mental conditions.博士（医学）・乙1331号・平成26年3月17

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

A novel fully covered metal stent for unresectable malignant distal biliary obstruction: results of a multicenter prospective study

Background/Aims Endoscopic self-expandable metal stent (SEMS) placement is currently the standard technique for treating unresectable malignant distal biliary obstructions (MDBO). Therefore, covered SEMS with longer stent patency and fewer migrations are required. This study aimed to assess the clinical performance of a novel, fully covered SEMS for unresectable MDBO. Methods This was a multicenter single-arm prospective study. The primary outcome was a non-obstruction rate at 6 months. The secondary outcomes were overall survival (OS), recurrent biliary obstruction (RBO), time to RBO (TRBO), technical and clinical success, and adverse events. Results A total of 73 patients were enrolled in this study. The non-obstruction rate at 6 months was 61%. The median OS and TRBO were 233 and 216 days, respectively. The technical and clinical success rates were 100% and 97%, respectively. Furthermore, the rate of occurrence of RBO and adverse events was 49% and 21%, respectively. The length of bile duct stenosis (<2.2 cm) was the only significant risk factor for stent migration. Conclusions The non-obstruction rate of a novel fully covered SEMS for MDBO is comparable to that reported earlier but shorter than expected. Short bile duct stenosis is a significant risk factor for stent migration

脂肪組織由来間葉系細胞はアミノ配糖体から有毛細胞を保護する

京都大学0048新制・課程博士博士(医学)甲第16735号医博第3683号新制||医||992(附属図書館)29410京都大学大学院医学研究科医学専攻(主査)教授 前川 平, 教授 吉村 長久, 教授 開 祐司学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDA

EI-2346, a Novel Interleukin-1.BETA.Converting Enzyme Inhibitor Produced by Streptomyces sp. E-2346: II. Structure Elucidation

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