Single C−F Bond Activation of the CF3 Group with a Lewis Acid: CF3‐Cyclopropanes as Versatile 4,4‐Difluorohomoallylating Agents

The selective activation of one C−F bond (single activation) of the CF3 group on cyclopropanes was achieved for the first time. When (trifluoromethyl)cyclopropanes were treated with arenes, allylsilanes, silyl enol ethers, or hydrosilanes in the presence of Me2AlCl, fluoride elimination and the subsequent ring opening proceeded to afford 4,4‐difluorohomoallylated products. In the absence of external nucleophiles, an alkyl group of AlR3 was effectively introduced to provide the corresponding 1,1‐difluoroalkenes

Unfolded protein response, activated by OASIS family transcription factors, promotes astrocyte differentiation

OASIS is a member of the CREB/ATF family of transcription factors and modulates cell- or tissue-specific unfolded protein response signalling. Here we show that this modulation has a critical role in the differentiation of neural precursor cells into astrocytes. Cerebral cortices of mice specifically deficient in OASIS (Oasis−/−) contain fewer astrocytes and more neural precursor cells than those of wild-type mice during embryonic development. Furthermore, astrocyte differentiation is delayed in primary cultured Oasis−/− neural precursor cells. The transcription factor Gcm1, which is necessary for astrocyte differentiation in Drosophila, is revealed to be a target of OASIS. Introduction of Gcm1 into Oasis−/− neural precursor cells improves the delayed differentiation of neural precursor cells into astrocytes by accelerating demethylation of the Gfap promoter. Gcm1 expression is temporally controlled by the unfolded protein response through interactions between OASIS family members during astrocyte differentiation. Taken together, our findings demonstrate a novel mechanism by which OASIS and its associated family members are modulated by the unfolded protein response to finely control astrocyte differentiation.This work was partly supported by grants from the Japan Society for the Promotion of Science KAKENHI (#22020030, #22800049), Sumitomo Foundation, Mochida Memorial Foundation for Medical and Pharmaceutical Research, Astellas Foundation for Research on Metabolic Disorders, Takeda Science Foundation, The Pharmacological Research Foundation Tokyo, Daiichi-Sankyo Foundation of Life Science, The Naito Foundation, Senri Life Science Foundation, Hokuto Foundation for Bioscience, and The Japan Prize Foundation

大腸杯細胞の最終分化における小胞体ストレスセンサーOASISの役割

広島大学(Hiroshima University)博士(医学)Doctor of Philosophy in Medical Sciencedoctora

Structural basis for dimer formation of human condensin structural maintenance of chromosome proteins and its implications for single-stranded DNA recognition

Eukaryotic structural maintenance of chromosome proteins (SMC) are major components of cohesin and condensins that regulate chromosome structure and dynamics during cell cycle. We here determine the crystal structure of human condensin SMC hinge heterodimer with ∼30 residues of coiled coils. The structure, in conjunction with the hydrogen exchange mass spectrometry analyses, revealed the structural basis for the specific heterodimer formation of eukaryotic SMC and that the coiled coils from two different hinges protrude in the same direction, providing a unique binding surface conducive for binding to single-stranded DNA. The characteristic hydrogen exchange profiles of peptides constituted regions especially across the hinge-hinge dimerization interface, further suggesting the structural alterations upon single-stranded DNA binding and the presence of a half-opened state of hinge heterodimer. This structural change potentially relates to the DNA loading mechanism of SMC, in which the hinge domain functions as an entrance gate as previously proposed for cohesin. Our results, however, indicated that this is not the case for condensins based on the fact that the coiled coils are still interacting with each other, even when DNA binding induces structural changes in the hinge region, suggesting the functional differences of SMC hinge domain between condensins and cohesin in DNA recognition.Susumu Uchiyama, Kazuki Kawahara, Yuki Hosokawa, Shunsuke Fukakusa, Hiroya Oki, Shota Nakamura, Yukiko Kojima, Masanori Noda, Rie Takino, Yuya Miyahara, Takahiro Maruno, Yuji Kobayashi, Tadayasu Ohkubo, Kiichi Fukui. Structural Basis for Dimer Formation of Human Condensin Structural Maintenance of Chromosome Proteins and Its Implications for Single-stranded DNA Recognition. Journal of Biological Chemistry, Volume 290, Issue 49, 2015, Pages 29461-29477. https://doi.org/10.1074/jbc.M115.670794

Safety and Complications of Medical Thoracoscopy

Objectives. To highlight the possible complications of medical thoracoscopy (MT) and how to avoid them. Methods. A retrospective and prospective analysis of 127 patients undergoing MT in Nagoya Medical Center (NMC) and Toyota Kosei Hospital. The data about complications was obtained from the patients, notes on the computer system, and radiographs. Results. The median age was 71.0 (range, 33.0–92.0) years and 101 (79.5%) were males. The median time with chest drain after procedure was 7.0 (range, 0.0–47.0) days and cases with talc poudrage were 30 (23.6%). Malignant histology was reported in 69 (54.3%), including primary lung cancer in 35 (27.5), mesothelioma in 18 (14.2), and metastasis in 16 (12.6). 58 (45.7%) revealed benign pleural diseases and TB was diagnosed in 15 (11.8%). 21 (16.5%) patients suffered from complications including lung laceration in 3 (2.4%), fever in 5 (3.9%) (due to hospital acquired infection (HAI) in 2, talc poudrage in 2, and malignancy in 1), HAI in 2 (1.6%), prolonged air-leak in 14 (11.0%), and subcutaneous emphysema in 1 (0.8%). Conclusions. MT is generally a safe procedure. Lung laceration is the most serious complication and should be managed well. HAI is of low risk and can be controlled by medical treatment

Safety and Complications of Medical Thoracoscopy

Objectives. To highlight the possible complications of medical thoracoscopy (MT) and how to avoid them. Methods. A retrospective and prospective analysis of 127 patients undergoing MT in Nagoya Medical Center (NMC) and Toyota Kosei Hospital. The data about complications was obtained from the patients, notes on the computer system, and radiographs. Results. The median age was 71.0 (range, 33.0–92.0) years and 101 (79.5%) were males. The median time with chest drain after procedure was 7.0 (range, 0.0–47.0) days and cases with talc poudrage were 30 (23.6%). Malignant histology was reported in 69 (54.3%), including primary lung cancer in 35 (27.5), mesothelioma in 18 (14.2), and metastasis in 16 (12.6). 58 (45.7%) revealed benign pleural diseases and TB was diagnosed in 15 (11.8%). 21 (16.5%) patients suffered from complications including lung laceration in 3 (2.4%), fever in 5 (3.9%) (due to hospital acquired infection (HAI) in 2, talc poudrage in 2, and malignancy in 1), HAI in 2 (1.6%), prolonged air-leak in 14 (11.0%), and subcutaneous emphysema in 1 (0.8%). Conclusions. MT is generally a safe procedure. Lung laceration is the most serious complication and should be managed well. HAI is of low risk and can be controlled by medical treatment

Clinical Study Safety and Complications of Medical Thoracoscopy

Objectives. To highlight the possible complications of medical thoracoscopy (MT) and how to avoid them. Methods. A retrospective and prospective analysis of 127 patients undergoing MT in Nagoya Medical Center (NMC) and Toyota Kosei Hospital. The data about complications was obtained from the patients, notes on the computer system, and radiographs. Results. The median age was 71.0 (range, 33.0-92.0) years and 101 (79.5%) were males. The median time with chest drain after procedure was 7.0 (range, 0.0-47.0) days and cases with talc poudrage were 30 (23.6%). Malignant histology was reported in 69 (54.3%), including primary lung cancer in 35 (27.5), mesothelioma in 18 (14.2), and metastasis in 16 (12.6). 58 (45.7%) revealed benign pleural diseases and TB was diagnosed in 15 (11.8%). 21 (16.5%) patients suffered from complications including lung laceration in 3 (2.4%), fever in 5 (3.9%) (due to hospital acquired infection (HAI) in 2, talc poudrage in 2, and malignancy in 1), HAI in 2 (1.6%), prolonged air-leak in 14 (11.0%), and subcutaneous emphysema in 1 (0.8%). Conclusions. MT is generally a safe procedure. Lung laceration is the most serious complication and should be managed well. HAI is of low risk and can be controlled by medical treatment