Chromosomal Dynamics at the Shh Locus: Limb Bud-Specific Differential Regulation of Competence and Active Transcription

The expression of Sonic hedgehog (Shh) in mouse limb buds is regulated by a long-range enhancer 1 Mb upstream of the Shh promoter. We used 3D-FISH and chromosome conformation capture assays to track changes at the Shh locus and found that long-range promoter-enhancer interactions are specific to limb bud tissues competent to express Shh. However, the Shh locus loops out from its chromosome territory only in the posterior limb bud (zone of polarizing activity or ZPA), where Shh expression is active. Notably, while Shh mRNA is detected throughout the ZPA, enhancer-promoter interactions and looping out were only observed in small fractions of ZPA cells. In situ detection of nascent Shh transcripts and unstable EGFP reporters revealed that active Shh transcription is likewise only seen in a small fraction of ZPA cells. These results suggest that chromosome conformation dynamics at the Shh locus allow transient pulses of Shh transcription

A framework for personalizing action history viewer

ABSTRACT This paper presents a programmable analysis and visualization framework for action histories, called mPATH framework. In ubiquitous computing environment, it is possible to infer human activities through various sensors and accumulate them. Visualization of such human activities is one of the key issues in terms of memory and sharing our experiences, since it acts as a memory assist when we recall, talk about, and report what we did in the past. However, current approaches for analysis and visualization are designed for a specific use, and therefore can not be applied to diverse use. Our approach provides users with programmability by a visual language environment for analyzing and visualizing the action histories. The framework includes icons representing data sources of action histories, analysis filters, and viewers. By composing them, users can create their own action history viewers. We also demonstrated several applications on the framework. The applications show the flexibility of creating action history viewers on the mPATH framework

Chromosomal Dynamics at the Shh Locus: Limb Bud-Specific Differential Regulation of Competence and Active Transcription

SummaryThe expression of Sonic hedgehog (Shh) in mouse limb buds is regulated by a long-range enhancer 1 Mb upstream of the Shh promoter. We used 3D-FISH and chromosome conformation capture assays to track changes at the Shh locus and found that long-range promoter-enhancer interactions are specific to limb bud tissues competent to express Shh. However, the Shh locus loops out from its chromosome territory only in the posterior limb bud (zone of polarizing activity or ZPA), where Shh expression is active. Notably, while Shh mRNA is detected throughout the ZPA, enhancer-promoter interactions and looping out were only observed in small fractions of ZPA cells. In situ detection of nascent Shh transcripts and unstable EGFP reporters revealed that active Shh transcription is likewise only seen in a small fraction of ZPA cells. These results suggest that chromosome conformation dynamics at the Shh locus allow transient pulses of Shh transcription

Does blended problem-based learning make Asian medical students active learners?:A prospective comparative study

Background: Asian educators have struggled to implement problem-based learning (PBL) because students rarely discuss their work actively and are not sufficiently engaged in self-directed learning. Supplementing PBL with additional e-learning, i.e. 'blended' PBL (bPBL), could stimulate students' learning process. Methods: We investigated the effects of bPBL on tutorial group functioning (discussion, self-efficacy, self-directed learning, active participation, and tutor's perceived authority) and students' level of acceptance of the e-learning elements. We compared PBL and bPBL in a medical university in Japan. In the bPBL condition, the tutor's instructions were replaced with online materials and short quizzes. After the course, a 13-item questionnaire using a 5-point Likert scale was distributed regarding the tutorial group functioning of the tutorial group (influence of discussion, self-efficacy, self-directed learning, active participation, and tutors' authority). The mean scores of subscales were compared with analysis of covariance. Knowledge levels were measured using a pre-test post-test design. A multiple regression analysis was performed to explore the association between e-learning acceptance and the subscales related to PBL. Results: Ninety-six students participated in the study (PBL: n = 24, bPBL: n = 72). Self-efficacy and motivation for learning triggered by group discussions was significantly higher for students in bPBL (p = 0.032 and 0.007, respectively). Knowledge gain in test scores was also significantly better in the bPBL condition (p = 0.026), and self-directed learning related positively to the acceptance of blended learning (p = 0.044). Conclusions: bPBL seemed more effective in promoting active learning and improving knowledge, without affecting tutors' authority. Implementing e-learning into PBL is suggested to be an effective strategy in the Asian context

Thalidomide Prevents the Progression of Peritoneal Fibrosis in Mice

Thalidomide is clinically recognized as a therapeutic agent for multiple myeloma and has been known to exert anti-angiogenic actions. Recent studies have suggested the involvement of angiogenesis in the progression of peritoneal fibrosis. The present study investigated the effects of thalidomide on the development of peritoneal fibrosis induced by injection of chlorhexidine gluconate (CG) into the mouse peritoneal cavity every other day for 3 weeks. Thalidomide was given orally every day. Peritoneal tissues were dissected out 21 days after CG injection. Expression of CD31 (as a marker of endothelial cells), proliferating cell nuclear antigen (PCNA), vascular endothelial growth factor (VEGF), α-smooth muscle actin (as a marker of myofibroblasts), type III collagen and transforming growth factor (TGF)-β was examined using immunohistochemistry. CG group showed thickening of the submesothelial zone and increased numbers of vessels and myofibroblasts. Large numbers of VEGF-, PCNA-, and TGF-β-positive cells were observed in the submesothelial area. Thalidomide treatment significantly ameliorated submesothelial thickening and angiogenesis, and decreased numbers of PCNA- and VEGF-expressing cells, myofibroblasts, and TGF-β-positive cells. Moreover, thalidomide attenuated peritoneal permeability for creatinine, compared to the CG group. Our results indicate the potential utility of thalidomide for preventing peritoneal fibrosis

Attaining Complete Remission May Confer a Better Outcome after Allogeneic Hematopoietic Stem Cell Transplantation in Adult Patients with Acute B-cell Lymphoblastic Leukemia

Introduction : Treatment outcome of adult patients with acute B-cell lymphoblastic leukemia (ALL) is suboptimal even after an allogeneic hematopoietic stem cell transplantation (allo-HSCT). To maximize the efficacies of this treatment strategy, risk stratification is crucial. Methods : We retrospectively collected clinical data of the adult patients with allo-HSCT for ALL at a single insitiution in Japan between 2003 and 2022. Univariate and multivariate analyses were performed to identify risk factors for overall survival (OS), progression-free survival (PFS) and GVHD-free-and-relapse-free survival (GRFS) at 3 years. Results : A total of 58 patients were included with 34 females and a median age of 39. Sixty-two percent of patients harbored high-risk cytogenetic features or Philadelphia chromosome (Ph). Hematologic complete response (CR) rate was 93 ％ after a first induction, but 75.9 ％ were in CR at allo-HSCT. Blinatumomab was used in 1.7 ％ of patients. A chimeric mRNA had been detected in 4 of 26 patients at allo-HSCT. The 3-year OS, PFS and GRFS were 72.7 ％, 54.7 ％ and 46.2 ％, respectively. Pre-transplantation CR was an independent risk factor. Discussion/Conclusions : Our results imply that a better OS may potentially be achieved by improved pretransplantation CR rate with more frequent application of novel agents.Article信州医学雑誌 71(5) : 257-267, (2023)journal articl

Azacitidine Treatment Following Intensive Chemotherapy with Daunorubicin and Cytarabin for Acute Transformation in Myelodysplastic/Myeloproliferative Neoplasms

Article信州医学雑誌 62(3):167-172(2014)journal articl

The Event Timing Finder for the Central Drift Chamber Level-1 Trigger at the Belle II experiment

The level-1 trigger system of the Belle II experiment is designed to select physics events of interest with almost 100% efficiency for hadronic events. In terms of event timing decision, the level-1 trigger is required to have an accuracy of less than 10 ns. The Central Drift Chamber (CDC) level-1 trigger provides the event timing information as one of the level-1 timing sources. We developed the new algorithm to measure the event timing with an accuracy of about 10 ns based on the CDC hit timing. Two-dimensional charged track reconstruction by Hough transformation was utilized to reduce high background hits. We used a new-developed general-purpose FPGA board (Universal Trigger board 4) for this module for the first time. We report the performance of the new algorithm using e$^+$e$^−$ collision data collected in 2020

Acquired dysfibrinogenemia: monoclonal λ-type IgA binding to fibrinogen caused lower functional plasma fibrinogen level and abnormal clot formation

ArticleInternational journal of hematology. 112(1): 96-104. (2020)journal articl