To understand how CD8 expression is regulated during the transition process from CD4+8+ (CD4 and CD8 double positive, DP) to CD4-8+ (CD8 single positive, CD8SP) cells in the thymus, the involvement of Runx proteins in the alteration of chromatin configuration was investigated. Using the chromatin immunoprecipitation assay, we first demonstrated that Runx proteins bind to the stage-specific CD8 enhancer, as well as the CD4 silencer, in CD8SP thymocytes. Among Runx family members, Runx3 expression was initiated in DP thymocytes receiving a positive selection signal and increased in concert with differentiation to the CD8SP stage. Furthermore, reactivation of the CD8 gene, as well as CD4 silencing, was suppressed in positively selected thymocytes of Runx dominant-negative transgenic mice. These results suggest that Runx proteins, especially Runx3, are involved in lineage specification of CD8 T cells and provide important information for understanding the mechanism for the mutually exclusive expression of coreceptors in mature thymocytes.

Background and Aims: Peroral endoscopic myotomy (POEM) is an available treatment modalities for achalasia. The reported efficacy of POEM in the only prospective multicenter study was 82%; however, a retrospective multicenter study in Japan reported a higher efficacy rate of 95%. The aim of this study was to prospectively verify treatment outcomes after POEM at multiple facilities in Japan. Methods: This was a prospective single-arm trial of POEM for achalasia at 8 facilities in Japan between April 2016 and March 2018 to evaluate its safety and efficacy. Patients were re-evaluated at 3 months and up to 1 year after POEM. Results: Among the 233 patients with achalasia who underwent POEM, procedure-related adverse events occurred in 24 patients (10.3%), none of whom required surgical intervention. In the 207 patients satisfying the inclusion criteria, the efficacy rate of POEM, defined by an Eckardt score 3 at 1 year, was 97.4% (95% CI, 95.3%-99.7%). The Eckardt score decreased significantly from 6.6 AE 2.0 preoperatively to 1.1 AE 1.1, 1 year after POEM. Postoperative reflux esophagitis, severe reflux esophagitis, and symptomatic GERD were reported in 54.2%, 5.6%, and 14.7%, respectively, and proton pump inhibitors were administered in 21.1%. Conclusions: Our prospective multicenter study in Japan showed greater efficacy of POEM for achalasia compared with the results of a previous prospective multicenter study. POEM is safe and highly effective for at least 1 year.

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The variation of velocity and volume transport of the Tsugaru Warm Current (TWC) is investigated based on the data of continuous and cross‐sectional current monitoring in the Tsugaru Strait. During November 1999–March 2000, the structure of the velocity transection across the strait was almost stable in which the TWC occupied the central part of the strait, while the returning flows existed in the northern and southern part of the strait, and the velocity of these flows decreases with time. The volume transport of the TWC varies from 2.1 to 1.1 Sv, with the mean value of 1.5 Sv, following the variation of the TWC. The temporal variation of the volume transport shows a linear correlation with that of the sea level difference between the Japan Sea and the Pacific Ocean. The contribution of the sea level difference to the volume transport is estimated to be roughly 70%.

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