MPP6 stimulates both RRP6 and DIS3 to degrade a specified subset of MTR4-sensitive substrates in the human nucleus

ヒト細胞内でRNA分解時に働く因子の役割を解明 --細胞内におけるRNA分解機構の全容解明に期待--. 京都大学プレスリリース. 2022-08-05.Recent in vitro reconstitution analyses have proven that the physical interaction between the exosome core and MTR4 helicase, which promotes the exosome activity, is maintained by either MPP6 or RRP6. However, knowledge regarding the function of MPP6 with respect to in vivo exosome activity remains scarce. Here, we demonstrate a facilitative function of MPP6 that composes a specific part of MTR4-dependent substrate decay by the human exosome. Using RNA polymerase II-transcribed poly(A)⁺ substrate accumulation as an indicator of a perturbed exosome, we found functional redundancy between RRP6 and MPP6 in the decay of these poly(A)⁺ transcripts. MTR4 binding to the exosome core via MPP6 was essential for MPP6 to exert its redundancy with RRP6. However, at least for the decay of our identified exosome substrates, MTR4 recruitment by MPP6 was not functionally equivalent to recruitment by RRP6. Genome-wide classification of substrates based on their sensitivity to each exosome component revealed that MPP6 deals with a specific range of substrates and highlights the importance of MTR4 for their decay. Considering recent findings of competitive binding to the exosome between auxiliary complexes, our results suggest that the MPP6-incorporated MTR4-exosome complex is one of the multiple alternative complexes rather than the prevailing one

Copper-Catalyzed Asymmetric Sulfonylative Desymmetrization of Glycerol

Glycerol is the main side product in the biodiesel manufacturing process, and the development of glycerol valorization methods would indirectly contribute the sustainable biodiesel production and decarbonization. Transformation of glycerol to optically active C3 units would be one of the attractive routes for glycerol valorization. We herein present the asymmetric sulfonylative desymmetrization of glycerol by using a CuCN/(R,R)-PhBOX catalyst system to provide an optically active monosulfonylated glycerol in high efficiency. A high degree of enantioselectivity was achieved with a commercially available chiral ligand and an inexpensive carbonate base. The optically active monosulfonylated glycerol was successfully transformed into a C3 unit attached with differentially protected three hydroxy moieties. In addition, the synthetic utility of the present reaction was also demonstrated by the transformation of the monosulfonylated glycerol into an optically active synthetic ceramide, sphingolipid E

Recent Results from LHD Experiment with Emphasis on Relation to Theory from Experimentalist’s View

he Large Helical Device (LHD) has been extending an operational regime of net-current free plasmas towardsthe fusion relevant condition with taking advantage of a net current-free heliotron concept and employing a superconducting coil system. Heating capability has exceeded 10 MW and the central ion and electron temperatureshave reached 7 and 10 keV, respectively. The maximum value of β and pulse length have been extended to 3.2% and 150 s, respectively. Many encouraging physical findings have been obtained. Topics from recent experiments, which should be emphasized from the aspect of theoretical approaches, are reviewed. Those are (1) Prominent features in the inward shifted configuration, i.e., mitigation of an ideal interchange mode in the configuration with magnetic hill, and confinement improvement due to suppression of both anomalous and neoclassical transport, (2) Demonstration ofbifurcation of radial electric field and associated formation of an internal transport barrier, and (3) Dynamics of magnetic islands and clarification of the role of separatrix

New criteria for multiple chemical sensitivity based on the Quick Environmental Exposure and Sensitivity Inventory developed in response to rapid changes in ongoing chemical exposures among Japanese.

Background & objectivesThe Quick Environmental Exposure and Sensitivity Inventory (QEESI) developed by Miller and Prihoda in the USA is used as a questionnaire for patients with multiple chemical sensitivity (MCS) in >10 countries. We developed a Japanese version of QEESI, assessed its reliability and validity, and defined original cut-off values for screening Japanese patients with MCS in 2003. Our recent study revealed that opportunities for exposure to various chemicals had increased for people in Japan, while subjective symptoms of MCS in patients had increased in severity. In this study, we considered new cut-off values that combined QEESI subscale scores based on the current situation in Japan.MethodsThe questionnaire used was a Japanese version of QEESI. The survey was conducted from 2012 to 2015. Participants were 111 patients with MCS (mean age: 46 ± 20, 81% female) initially diagnosed by physicians, and 444 age- and gender-matched controls not diagnosed with MCS by doctors. The discriminatory validity of QEESI scores of patients and controls were evaluated by logistic regression and receiver operating characteristic analyses when considering interactions of the Masking Index (ongoing chemical exposure). New combined cut-off values were then set.ResultsNew combined cut-off values (meeting conditions of Chemical Intolerances ≥ 30, Symptom Severity ≥ 13, and Life Impacts ≥ 17) showed high sensitivity (82.0%) and specificity (94.4%). Using new criteria when considering ongoing chemical exposure, study participants were categorized as: Very suggestive, Somewhat suggestive, Problematic, and Not suggestive. Participants classified as Very suggestive included 25 (5.6%) controls.ConclusionsWe have set new criteria with combined cut-off values based on current Japanese conditions. Such new criteria can be used for screening and as a diagnostic aid for Japanese patients with MCS and suggest approximately 6% of the Japanese general population may be classified as "Very suggestive people with MCS"

Comparison of environmental intolerances and symptoms between patients with multiple chemical sensitivity, subjects with self-reported electromagnetic hypersensitivity, patients with bronchial asthma, and the general population

Abstract Background Environmental hypersensitivity/intolerance is considered closely related to allergic diseases. To understand these conditions, the environmental intolerances and symptoms of patients with multiple chemical sensitivity (MCS), subjects with self-reported electromagnetic hypersensitivity (EHS), patients with bronchial asthma (BA), and the general population were compared using universal questionnaires. Methods A survey was conducted from 2012 to 2015. The subjects were categorized in four groups: 111 patients with physician-diagnosed MCS, 119 subjects with self-reported EHS, patients with 98 physician-diagnosed BA, and 619 controls from general population. The Quick Environmental Exposure and Sensitivity Inventory and EHS questionnaire were used. The differences between the questionnaire scores among the four groups were tested using logistic regression analyses adjusted for age and gender as covariates. Results The MCS and EHS groups had significantly high scores of intolerances to multiple environmental factors, life impact, and multiple symptoms than the BA and control groups. Although the differences between most of these scores of the MCS and EHS groups were not significant, the electromagnetic hypersensitivity reaction was significantly higher in the EHS group than in the MCS group. In addition, the scores for intolerances to chemicals and other compounds, life impact, and several symptoms of the BA group were significantly higher than those of the control group. Conclusions This study clarified the similarities and differences of the environmental intolerances and symptoms between the four groups

Clinical significance of ALKBH4 expression in non-small cell lung cancer

BACKGROUND: Gene methylation is deeply involved in epigenetics and affects both the development and maintenance of homeostasis and carcinogenesis. ALKBH4 is a member of the AlkB homolog (ALKBH) family that controls demethylation of DNA and RNA. METHODS: This study enrolled 160 patients with non-small cell lung cancer (NSCLC) who underwent complete resection. The expression of ALKBH4 in cancer tissue was evaluated by immunohistochemistry. The correlation among the expression of ALKBH4, clinicopathological factors, and prognostic outcome was evaluated. RESULTS: In the NSCLC clinical samples, the expression of ALKBH4 was identified not only in cell membranes but also in the cytoplasm of cancer cells. In 140 of 160 cases, ALKBH4 was more highly expressed in the cancerous tissue than in the surrounding normal tissue. The proportion of cancer cells expressing ALKBH4 was higher in adenocarcinoma than in other histological types. In addition, the expression intensity of ALKBH4 in each cancer cell was also stronger in adenocarcinoma than in squamous cell carcinoma. The expression of ALKBH4 was not associated with clinicopathological factors, except for histological type. In adenocarcinoma, the recurrence-free survival (RFS) and overall survival (OS) rates were significantly lower in the ALKBH4-positive group than in the ALKBH4-negative group (P=0.008, 0.031, respectively). A multivariate logistic regression analysis indicated that the ALKBH4 expression was an independent prognostic factor for RFS (P=0.003) and OS (P=0.013). The expression of ALKBH4 was observed in all four patients with adenocarcinoma in situ. CONCLUSIONS: The ALKBH4 expression may be a useful predictor of the postoperative outcomes of lung adenocarcinoma (LUAD) patients