Iridium-catalyzed α-selective deuteration of alcohols

新規重水素化触媒反応を開発 --医薬品への直接重水素導入を達成--. 京都大学プレスリリース. 2022-07-21.The development of chemoselective C(sp³)-H deuteration is of particular interest in synthetic chemistry. We herein report the α-selective, iridium(III)-bipyridonate-catalyzed hydrogen(H)/deuterium(D) isotope exchange of alcohols using deuterium oxide (D₂O) as the primary deuterium source. This method enables the direct, chemoselective deuteration of primary and secondary alcohols under basic or neutral conditions without being affected by coordinative functional groups such as imidazole and tetrazole. Successful substrates for deuterium labelling include the pharmaceuticals losartan potassium, rapidosept, guaifenesin, and diprophylline. The deuterated losartan potassium shows higher stability towards the metabolism by CYP2C9 than the protiated analogue. Kinetic and DFT studies indicate that the direct deuteration proceeds through dehydrogenation of alcohol to the carbonyl intermediate, conversion of [Ir[III]–H] to [Ir[III]−D] with D₂O, and deuteration of the carbonyl intermediate to give the α-deuterated product

The origin of infra-slow oscillations of oxygenated hemoglobin observed in functional near-infrared spectroscopy

There is increasing interest in the intrinsic activity of the resting brain, especially the activity slower than 0.1Hz (i.e., low-frequency oscillations, or LFOs). To investigate the origin of LFOs observed in functional near-infrared spectroscopy (fNIRS), we recorded multichannel fNIRS and electroencephalography (EEG) from the frontal cortex of 11 healthy young volunteers in the resting state. Electrocardiography (ECG), electro-oculography and respiration were also measured. Synchronous oscillations of oxy-hemoglobin (oxy-Hb) around 1.0Hz were detected in all fNIRS channels, and their frequency was consistent with a peak frequency of ECG, suggesting the changes of cerebral blood flow due to heart beats. In addition, oxy-Hb oscillations around 0.1Hz (i.e., LFOs) appeared in the fNIRS. The channels where LFOs appeared differed among the subjects, and the LFOs appeared or disappeared even in the same fNIRS channels. The appearance of LFOs in fNIRS channels was significantly higher when the LFOs appeared on the EEG in the adjacent EEG electrodes compared to when LFOs did not appear on EEG. The amplitude and coherence (synchronicity) of the LFOs were increased by changing the subjects' position from dorsal to the sitting position in both fNIRS and EEG, and the coherence in particular was increased in the homologous fNIRS channels on the bilateral hemispheres. These results suggest that LFOs of oxy-Hb couple with resting-state EEG activity

The Expression Level of HIV-1 Vif Is Optimized by Nucleotide Changes in the Genomic SA1D2prox Region during the Viral Adaptation Process

HIV-1 Vif plays an essential role in viral replication by antagonizing anti-viral cellular restriction factors, a family of APOBEC3 proteins. We have previously shown that naturally-occurring single-nucleotide mutations in the SA1D2prox region, which surrounds the splicing acceptor 1 and splicing donor 2 sites of the HIV-1 genome, dramatically alter the Vif expression level, resulting in variants with low or excessive Vif expression. In this study, we investigated how these HIV-1 variants with poor replication ability adapt and evolve under the pressure of APOBEC3 proteins. Adapted clones obtained through adaptation experiments exhibited an altered replication ability and Vif expression level compared to each parental clone. While various mutations were present throughout the viral genome, all replication-competent adapted clones with altered Vif expression levels were found to bear them within SA1D2prox, without exception. Indeed, the mutations identified within SA1D2prox were responsible for changes in the Vif expression levels and altered the splicing pattern. Moreover, for samples collected from HIV-1-infected patients, we showed that the nucleotide sequences of SA1D2prox can be chronologically changed and concomitantly affect the Vif expression levels. Taken together, these results demonstrated the importance of the SA1D2prox nucleotide sequence for modulating the Vif expression level during HIV-1 replication and adaptation

The Effects of Volcanic Disaster on the Prevalence and Severity of Bronchial Asthma

Objectives: To evaluate the impact of volcanic disaster on bronchial asthma, the prevalence and the extent of deterioration of asthma were studied among primary school children aged 6 to 11 years who experienced the volcanic eruption of Mt. Unzen Fugen, Nagasaki, Japan. Methods: Questionnaire data were collected from the parents or guardians of primary school children. Asthma was classified into four categories: diagnosed asthma, current asthma, remitted asthma, and deteriorated asthma, and the prevalence of each category was compared according to sex and grade. We also analyzed the relation between asthma and past illness and family history including experience of volcanic disaster. Results: Multiple logistic regression analysis showed that past illnesses of allergic diseases, such as allergic rhinitis, dermatitis and conjunctivitis were associated with either current asthma or deteriorated asthma. On the effects of volcanic disaster, a change of family member after volcanic disaster was significantly associated with deteriorated asthma (odds ratio=3.20, 95% confidence interval=1.79-5.70). Location of school seemed to somewhat influence the prevalence of deteriorated asthma, which might relate to the distance from the volcanic crater. Conclusion: Our findings suggest that not only gases and ash but also changes in psychosocial conditions by refuge or related anxiety may influence the prevalence of asthma among primary school children

Clinical significance of soluble CADM1 as a novel marker for adult T-cell leukemia/lymphoma

Adult T-cell leukemia/leukemia (ATLL) is an aggressive peripheral T-cell malignancy, caused by infection with the human T-cell leukemia virus type 1 (HTLV-1). We have recently shown that cell adhesion molecule 1 (CADM1), a member of the immunoglobulin superfamily, is specifically and consistently overexpressed in ATLL cells, and functions as a novel cell surface marker. In this study, we first show that a soluble form of CADM1 (sCADM1) is secreted from ATLL cells by mainly alternative splicing. After developing the Alpha linked immunosorbent assay (AlphaLISA) for sCADM1, we showed that plasma sCADM1 concentrations gradually increased during disease progression from indolent to aggressive ATLL. Although other known biomarkers of tumor burden such as soluble interleukin-2 receptor α (sIL-2Rα) also increased with sCADM1 during ATLL progression, multivariate statistical analysis of biomarkers revealed that only plasma sCADM1 was selected as a specific biomarker for aggressive ATLL, suggesting that plasma sCADM1 may be a potential risk factor for aggressive ATLL. In addition, plasma sCADM1 is a useful marker for monitoring response to chemotherapy as well as for predicting relapse of ATLL. Furthermore, the change in sCADM1 concentration between indolent and aggressive type ATLL was more prominent than the change in the percentage of CD4+CADM1+ ATLL cells. As plasma sCADM1 values fell within normal ranges in HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients with higher levels of serum sIL-2Rα, a measurement of sCADM1 may become a useful tool to discriminate between ATLL and other inflammatory diseases, including HAM/TSP

リアルタイムMRI動画日本語調音運動データベースの設計

National Institute for Japanese Language and LinguisticsNational Institute for Japanese Language and LinguisticsWaseda UniversityNational Institute for Japanese Language and LinguisticsATR-PromotionsATR-PromotionsChiba Institute of TechnologyKonan UniversityTakushoku UniversityNational Institute for Japanese Language and LinguisticsNational Institute for Japanese Language and LinguisticsWaseda UniversityWaseda UniversityPicolab会議名: 言語資源活用ワークショップ2020, 開催地: オンライン, 会期: 2020年9月8日−9日, 主催: 国立国語研究所 コーパス開発センターわれわれは、日本語に関する調音音声学的研究の新しいインフラ提供をめざして、調音運動データベースの構築を進めてきている。声道全体の形状変化を毎秒14 ないし25 フレームのリアルタイムMRI 動画として記録したデータが、現時点で東京方言16 名、近畿方言5名分収録済である。1 名あたりの発話量は25〜30 分である。データには個々の発話の開始時刻と終了時刻のタグが付与されており、他に発話内容と話者に関するメタデータを検索に利用できる