Trans-omics Impact of Thymoproteasome in Cortical Thymic Epithelial Cells

The thymic function to produce self-protective and self-tolerant T cells is chiefly mediated by cortical thymic epithelial cells (cTECs) and medullary TECs (mTECs). Recent studies including single-cell transcriptomic analyses have highlighted a rich diversity in functional mTEC subpopulations. Because of their limited cellularity, however, the biochemical characterization of TECs, including the proteomic profiling of cTECs and mTECs, has remained unestablished. Utilizing genetically modified mice that carry enlarged but functional thymuses, here we show a combination of proteomic and transcriptomic profiles for cTECs and mTECs, which identified signature molecules that characterize a developmental and functional contrast between cTECs and mTECs. Our results reveal a highly specific impact of the thymoproteasome on proteasome subunit composition in cTECs and provide an integrated trans-omics platform for further exploration of thymus biology

Comparison of Mid-term Angiographic and Clinical Outcomes Following Zotarolimus-eluting Stent and Paclitaxel-eluting Stent Implantation Based on Lesion Complexity

First-generation drug-eluting stents (DESs) have reduced angiographic and clinical restenosis rates compared to bare-metal stents (BMSs). Zotarolimus-eluting stents (ZESs) are second-generation drug-eluting stents: however, the clinical efficacy of ZES implantation is unclear because late loss associated with ZESs is reportedly higher than that observed for other DESs. The aim of this study was to evaluate the clinical efficacy of ZESs compared to paclitaxel-eluting stents (PESs). We retrospectively evaluated the angiographic and clinical outcomes of 431 lesions in 342 patients treated with PESs and 153 lesions in 121 patients treated with ZESs in our hospital between May 2007 and December 2010. Follow-up angiographic examinations were performed eight months post-treatment and clinical outcomes were assessed one year after the procedure. Quantitative coronary angiographic analyses showed that late loss was significantly higher for ZESs than PESs (0.82 ± 0.73 mm vs 0.47 ± 0.68 mm; P = 0.003). However, there was no significant difference in target lesion revascularization (TLR) between the two groups (ZES: 15 lesions, 9.8% vs PES: 25 lesions, 5.8%; P = 0.092). When comparing stents according to the American College of Cardiology/American Heart Association (ACC/AHA) lesion type, the TLR rate in the ZES group was significantly lower than in the PES group (0% vs 7.0%; P = 0.038) for Type A/B1 lesions, but the TLR rate for type B2/C lesions in the ZES group was significantly higher than in the PES group (15.8% vs 5.3%; P = 0.009). Multivariate logistic regression analysis showed that dialysis (OR: 35.54; 95% CI: 3.15-400.67; P = 0.039) and pre-minimal lumen diameter (OR: 0.036; 95% CI: 0.002-0.541; P = 0.016) were independent predictors of TLR in ZES-treated lesions. However, no factors predicted TLR in PES-treated lesions. Our study demonstrated excellent outcomes with ZESs for simple lesions, but it is necessary to carefully implant ZESs in complex lesions, such as ACC/AHA type B2/C lesions

Risk Factors for Restenosis after Percutaneous Coronary Intervention with Sirolimus- and Paclitaxel-eluting Stents

To identify risk factors for restenosis after percutaneous coronary intervention with sirolimus (SES)- or paclitaxel (PES)-eluting stents. The clinical outcomes of 894 patients treated with either SES (n = 462) or PES (n = 432) between January 2005 and January 2010 were evaluated. Multivariate logistic regression analysis showed that long ( > 20mm)(odds ratio [OR], 1.87; 95% confidence interval [CI], 1.07-3.33; P = 0.03) or bent (angle > 45°) lesions (OR, 2.57; 95% CI, 1.47- 4.49; P < 0.01) were independent risk factors for restenosis with SES, and that hemodialysis (OR, 7.61; 95% CI, 2.78- 20.85; P < 0.01) and long (OR, 2.63; 95% CI, 1.18-5.84; P = 0.02) or bent lesions (OR, 3.47; 95% CI, 1.65-7.27;P < 0.01) were independent risk factors for target lesion revascularization (TLR) with SES. In contrast, no independent risk factors for restenosis and TLR were found for lesions treated with PES. The rate of TLR was significantly higher in patients on hemodialysis or in those with long lesions in the SES group (hemodialysis, 30.4% vs. 11.1%, P = 0.02; long lesions, 13.2% vs. 4.4%, P < 0.01; for SES vs. PES, respectively). Rates of restenosis and TLR were significantly higher in patients with bent lesions in the SES group (restenosis, 30.8% vs. 15.6%, P < 0.01; TLR, 20.0% vs. 5.8%, P < 0.01; for SES and PES, respectively). Most clinical studies have described better angiographic results for SES compared to PES. However, PES might result in better clinical outcomes than SES for patients on hemodialysis or for those with long or bent lesions

Significance of Coronary Artery Calcium Score in the Target Lesion Evaluated by Multi-detector Computed Tomography for Selecting Treatment of Rotational Atherectomy in Patients with Coronary Artery Disease

We investigated whether coronary artery calcium score (CAC) in the target lesion on the multidetector computed tomography angiography (CTA) predicts the addition of the Rotational atherectomy (Rota) during percutaneous coronary intervention (PCI). Lesion CAC on CTA were evaluated with quantitative coronary analysis (QCA) on coronary angiography for predicting the Rota treatment in 114 consecutive patients (165 target lesions) with first PCI (68 ± 9 years old, females: 17.6%). Rota was added in 8 patients (11 lesions). The lesion length and diameter stenosis on QCA, and lesion length and lesion CAC on CTA were the primary factors associated with the addition of Rota. Using the cut-off value based on receiver operating characteristic analysis, the sensitivity and specificity for predicting the Rota based on QCA was 72.7% in 8 of 11 lesions (vessels) with Rota and the specificity was 74% in 114 of 154 without Rota in the lesion length of ≥ 23mm (χ2=10.9, p=0.001), and 54.5% in 6 of 11 lesions with Rota and the specificity was 79.2% in 122 of 154 without Rota in the diameter stenosis of ≥ 83% (χ2=6.6, p=0.01). Those based on CTA were 90.9% in 10 of 11 lesions with Rota and 77.3% in 119 of 154 without Rota in the lesion length of ≥ 34mm (χ2=24.1, p<0.001), and 90.9% in 10 of 11 with Rota and 88.3% in 136 of 154 without Rota in the lesions with CAC ≥453 (χ2=45.7, p<0.001). Lesion CAC on CTA is most predictive of addition of Rota during PCI

ダイガク ボランティア カンレン ソシキ ニヨル ガクセイ ボランティア カツドウ ノ ジッサイ

東日本大震災から現在に至るまでのこの期間（研究期間[2016－2017年]）、この震災について大学教員が大学生にどのように語ってきたのか、また大学の教学システムは学生にどのような影響を与えてきたのか、十分に検討されてきたとは言えない状況であった。本研究では、ボランティアに関する大学教育のあり方を大学組織の立場から検討することを目的とし、震災ボランティアに学生を派遣している各大学のボランティアステーション・スタッフへの調査をもとに、その活動の実態把握を行った。結果、ボランティア関連組織を設立していた大学においては、学生にとってのボランティアの有用性が意識されており、自治体との連携や大学間連携が進みつつある現状が明らかとなったが、学内の体制整備、移動費など費用の工面、学生ボランティアの安全確保、被災地域となった場合のボランティアコーディネート能力の向上などが課題として認識されていた

Characterization of the Testis-specific Proteasome Subunit α4s in Mammals

Frontal view of the High Altar, with painting by Guglielmo Cortese, Crucifixion of St. Andrew (1668), depicting the martyrdom of the saint; Sant' Andrea al Quirinale was a project for the Jesuits funded by Prince Camillo Pamphili. It is oval in plan, with the entrance and the altar facing one another on the short axis. Framed by massive pairs of dusty-pink marble columns, with an eccentric inward-curving pediment, the altar aedicule is the focal point of the interior. Source: Grove Art Online; http://www.groveart.com/ (accessed 11/20/2007

Rpn10-Mediated Degradation of Ubiquitinated Proteins Is Essential for Mouse Development▿

Rpn10 is a subunit of the 26S proteasome that recognizes polyubiquitinated proteins. The importance of Rpn10 in ubiquitin-mediated proteolysis is debatable, since a deficiency of Rpn10 causes different phenotypes in different organisms. To date, the role of mammalian Rpn10 has not been examined genetically. Moreover, vertebrates have five splice variants of Rpn10 whose expressions are developmentally regulated, but their biological significance is not understood. To address these issues, we generated three kinds of Rpn10 mutant mice. Rpn10 knockout resulted in early-embryonic lethality, demonstrating the essential role of Rpn10 in mouse development. Rpn10a knock-in mice, which exclusively expressed the constitutive type of Rpn10 and did not express vertebrate-specific variants, grew normally, indicating that Rpn10 diversity is not essential for conventional development. Mice expressing the N-terminal portion of Rpn10, which contained a von Willebrand factor A (VWA) domain but lacked ubiquitin-interacting motifs (Rpn10ΔUIM), also exhibited embryonic lethality, suggesting the important contribution of UIM domains to viability, but survived longer than Rpn10-null mice, consistent with a “facilitator” function of the VWA domain. Biochemical analysis of the Rpn10ΔUIM liver showed specific impairment of degradation of ubiquitinated proteins. Our results demonstrate that Rpn10-mediated degradation of ubiquitinated proteins, catalyzed by UIMs, is indispensable for mammalian life