138 research outputs found

    Localization of cyclophilin A and cyclophilin C mRNA in murine kidney using RT-PCR

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    Localization of cyclophilin A and cyclophilin C mRNA in murine kidney using RT-PCR. Cyclosporin A (CsA), which is widely used as an immunosuppressant, has a nephrotoxic side effect. The mechanism of this nephrotoxicity is not well understood; however, recent studies suggest that cyclophilin (cyp) is responsible for mediating the immunosuppressive action of CsA through the interaction with the Ca2+ - and calmodulin-dependent phosphatase, calcineurin. While cyp A mRNA is expressed ubiquitously, cyp C mRNA has been shown to be topically expressed, including in the kidney. We examined: (1) distribution of cyp A and cyp C mRNA in microdissected murine nephron segments, using a combination of reverse transcription and polymerase chain reaction (RT-PCR) techniques, and (2) the effect of CsA administration on cyp C mRNA expression in proximal convoluted tubule. Among the nephron segments examined, large signals for cyp C PCR product were detected in proximal convoluted tubule and proximal straight tubule. Our data showed that the distribution of cyp C mRNA was uneven, and it mainly existed in segments that are relatively sensitive to CsA toxicity. In contrast, cyp A mRNA was found to be distributed almost equally along the nephron segments examined. By CsA administration, the signal for cyp C mRNA PCR product was increased. These results suggest that cyp C may play some role in the renal tubular disorder observed in CsA nephrotoxicity

    Novel function of HATs and HDACs in homologous recombination through acetylation of human RAD52 at double-strand break sites

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    The p300 and CBP histone acetyltransferases are recruited to DNA double-strand break (DSB) sites where they induce histone acetylation, thereby influencing the chromatin structure and DNA repair process. Whether p300/CBP at DSB sites also acetylate non-histone proteins, and how their acetylation affects DSB repair, remain unknown. Here we show that p300/CBP acetylate RAD52, a human homologous recombination (HR) DNA repair protein, at DSB sites. Using in vitro acetylated RAD52, we identified 13 potential acetylation sites in RAD52 by a mass spectrometry analysis. An immunofluorescence microscopy analysis revealed that RAD52 acetylation at DSBs sites is counteracted by SIRT2- and SIRT3-mediated deacetylation, and that non-acetylated RAD52 initially accumulates at DSB sites, but dissociates prematurely from them. In the absence of RAD52 acetylation, RAD51, which plays a central role in HR, also dissociates prematurely from DSB sites, and hence HR is impaired. Furthermore, inhibition of ataxia telangiectasia mutated (ATM) protein by siRNA or inhibitor treatment demonstrated that the acetylation of RAD52 at DSB sites is dependent on the ATM protein kinase activity, through the formation of RAD52, p300/CBP, SIRT2, and SIRT3 foci at DSB sites. Our findings clarify the importance of RAD52 acetylation in HR and its underlying mechanism

    Association between self-reported walking speed and calcaneal stiffness index in postmenopausal Japanese women

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    Background: Osteoporosis and related fractures, a worldwide public health issue of growing concern, is characterized by compromised bone strength and an increased risk of fracture. Here we show an association between self-reported walking speed and bone mass among community-dwelling postmenopausal Japanese women aged 50 years and older. Design; cross-sectional study: Setting and Participants; The survey population included 1008 postmenopausal women 50?92 years of age residing in rural communities. Methods: Self-reported walking speed was ascertained by asking the participants: “Is your walking speed faster than others of the same age and sex?” to which participants responded “yes (faster)” or “no (moderate/slower).” Calcaneal stiffness index was measured. Results: Women with a faster self-reported walking speed were younger and had a lower BMI, higher stiffness index, and higher grip strength than women with a slower walking speed. Multiple linear regression analysis adjusted for age, BMI, grip strength, comorbidity, current smoking, and alcohol drinking status showed a significant association between faster self-reported walking speed and higher calcaneal stiffness index (p < 0.001). Conclusions: Our findings suggest that questionnaires of walking speed may be useful for predicting bone mass and that a fast self-reported walking may benefit bone health in postmenopausal women

    ジュニア期スポーツにおけるサプリメント摂取の現状とその影響

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    近年、多種類のサプリメントが簡単に入手できる時代となり、子どもたちも自由に気軽に購入できる状況におかれている。また、スポーツ界ではアンチ・ドーピング活動が盛んとなっているが、サプリメント摂取はアスリートにとってドーピング的意味合いを持つことを忘れてはならない。そこで、我々は、まず子どものサプリメントの摂取状況を文献的に考察し、次いで全国の日本スポーツ少年団に登録する子どもを対象としたサプリメント等に関するアンケート調査を実施した結果を踏まえて、子どもたちのサプリメント摂取やドーピングに関する今後の課題を検討した。その結果、サプリメント摂取はスポーツに対する効果だけでなく、ドーピング問題も含めた教育をジュニア期から行い、専門家による早急な対応の必要性が明らかとなった

    Entanglement generation by communication using squeezed states

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    In order to improve the error probability of generating entanglement by communication for quantum computation, we propose the use of squeezed light. When generating entanglement between two atoms by communication, the error probability can be reduced by increasing the distance between quantum states of probe light in phase space. The phase rotation of light depends on the atom-photon coupling strength and the light amplitude, which are limited in practice. A large error probability has been expected for coherent probe light. If we assume typical values of light amplitude and phase rotation, alpha = 100 and theta = 0.01, the error probability is estimated to be P-coh((min)) = 0.14 and P-coh((hom)) = 0.23 for minimum error discrimination and homodyne measurements. The error probability can be reduced to P-squ((min)) = 1.73 x 10(-8) and P-squ((hom)) = 4.09 x 10(-5) using squeezed coherent light, where the same values of the mean photon number and the phase rotation angle are assumed for the coherent light probe. These values satisfy the requirements for scalable quantum computation
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