Probing Higgs self-coupling of a classically scale invariant model in e+e−→Zhhe^+e^- \to Zhh: Evaluation at physical point

A classically scale invariant extension of the standard model predicts large anomalous Higgs self-interactions. We compute missing contributions in previous studies for probing the Higgs triple coupling of a minimal model using the process $e^+e^- \to Zhh$. Employing a proper order counting, we compute the total and differential cross sections at the leading order, which incorporate the one-loop corrections between zero external momenta and their physical values. Discovery/exclusion potential of a future $e^+e^-$ collider for this model is estimated. We also find a unique feature in the momentum dependence of the Higgs triple vertex for this class of models.Comment: 14 pages, 7 figures; Version to appear in Phys. Lett.

Single-Cell Transcriptome Analysis Dissects the Replicating Process of Pancreatic Beta Cells in Partial Pancreatectomy Model

膵臓ベータ細胞の増殖プロセスを時系列解析 --糖尿病の新規治療開発に期待--. 京都大学プレスリリース. 2020-12-24.Heterogeneity of gene expression and rarity of replication hamper molecular analysis of β-cell mass restoration in adult pancreas. Here, we show transcriptional dynamics in β-cell replication process by single-cell RNA sequencing of murine pancreas with or without partial pancreatectomy. We observed heterogeneity of Ins1-expressing β-cells and identified the one cluster as replicating β-cells with high expression of cell proliferation markers Pcna and Mki67. We also recapitulated cell cycle transition accompanied with switching expression of cyclins and E2F transcription factors. Both transient activation of endoplasmic reticulum stress responders like Atf6 and Hspa5 and elevated expression of tumor suppressors like Trp53, Rb1, and Brca1 and DNA damage responders like Atm, Atr, Rad51, Chek1, and Chek2 during the transition to replication associated fine balance of cell cycle progression and protection from DNA damage. Taken together, these results provide a high-resolution map depicting a sophisticated genetic circuit for replication of the β-cells

Characterisation of Ppy-lineage cells clarifies the functional heterogeneity of pancreatic beta cells in mice

Aims/hypothesis Pancreatic polypeptide (PP) cells, which secrete PP (encoded by the Ppy gene), are a minor population of pancreatic endocrine cells. Although it has been reported that the loss of beta cell identity might be associated with beta-to-PP cell-fate conversion, at present, little is known regarding the characteristics of Ppy-lineage cells. Methods We used Ppy-Cre driver mice and a PP-specific monoclonal antibody to investigate the association between Ppy-lineage cells and beta cells. The molecular profiles of endocrine cells were investigated by single-cell transcriptome analysis and the glucose responsiveness of beta cells was assessed by Ca2+ imaging. Diabetic conditions were experimentally induced in mice by either streptozotocin or diphtheria toxin. Results Ppy-lineage cells were found to contribute to the four major types of endocrine cells, including beta cells. Ppy-lineage beta cells are a minor subpopulation, accounting for 12–15% of total beta cells, and are mostly (81.2%) localised at the islet periphery. Unbiased single-cell analysis with a Ppy-lineage tracer demonstrated that beta cells are composed of seven clusters, which are categorised into two groups (i.e. Ppy-lineage and non-Ppy-lineage beta cells). These subpopulations of beta cells demonstrated distinct characteristics regarding their functionality and gene expression profiles. Ppy-lineage beta cells had a reduced glucose-stimulated Ca2+ signalling response and were increased in number in experimental diabetes models. Conclusions/interpretation Our results indicate that an unexpected degree of beta cell heterogeneity is defined by Ppy gene activation, providing valuable insight into the homeostatic regulation of pancreatic islets and future therapeutic strategies against diabetes

Identification of oxidative stress-regulated genes in rat aortic smooth muscle cells by suppression subtractive hybridization

AbstractA suppression subtractive hybridization technique was used to identify reactive oxygen species (ROS)-regulated genes in rat vascular smooth muscle cells. Three genes out of 89 clones, identified as fibronectin, p105 coactivator and ECA39, showed increased expression after treatment with H2O2. The mRNA expressions of these three genes were induced in a time- and dose-dependent manner, independent of protein kinase C activation. Immunohistochemical staining showed that the p105 coactivator expression was markedly induced in the neointima of balloon-injured rat carotid arteries. These results suggest that ROS may play an important role in the development of atherosclerosis by regulating the gene expressions we identified in this study

Prevalence of Amiodarone-Induced Thyrotoxicosis and Associated Risk Factors in Japanese Patients

Amiodarone is a widely used agent for life-threatening arrhythmias. Although amiodarone-induced thyrotoxicosis (AIT) is a major adverse effect that can cause recurrence of arrhythmias and exacerbation of heart failure, risk factors for AIT among amiodarone-treated Japanese patients have not been elucidated. Here, we investigated the prevalence and predictive factors for AIT. The study subjects were 225 patients treated with amiodarone between 2008 and 2012, who were euthyroid before amiodarone therapy. All patients with AIT were diagnosed by measurement of thyroid hormones and ultrasonography. Among the 225 subjects, 13 patients (5.8%) developed AIT and all the patients were classified as Type 2 AIT. Baseline features of patients with AIT were not different from those who did not develop AIT, except for age (AIT, 55.1 ± 13.8, non-AIT, 68.1 ± 12.0 years, P<0.001). Multivariate analyses using the Cox proportional hazard model identified age as the sole determinant of AIT (hazard ratio: 0.927, 95% confidence interval: 0.891–0.964). Receiver operating characteristic curve analysis identified age of 63.5 years as the cutoff value for AIT with sensitivity of 70.3% and specificity of 69.2%. In summary, this study showed that the prevalence of AIT is 5.8% in Japanese patients treated with amiodarone and that young age is a risk factor for AIT

COVID-19 vaccine effectiveness against severe COVID-19 requiring oxygen therapy, invasive mechanical ventilation, and death in Japan: A multicenter case-control study (MOTIVATE study).

INTRODUCTION: Since the SARS-CoV-2 Omicron variant became dominant, assessing COVID-19 vaccine effectiveness (VE) against severe disease using hospitalization as an outcome became more challenging due to incidental infections via admission screening and variable admission criteria, resulting in a wide range of estimates. To address this, the World Health Organization (WHO) guidance recommends the use of outcomes that are more specific to severe pneumonia such as oxygen use and mechanical ventilation. METHODS: A case-control study was conducted in 24 hospitals in Japan for the Delta-dominant period (August-November 2021; "Delta") and early Omicron (BA.1/BA.2)-dominant period (January-June 2022; "Omicron"). Detailed chart review/interviews were conducted in January-May 2023. VE was measured using various outcomes including disease requiring oxygen therapy, disease requiring invasive mechanical ventilation (IMV), death, outcome restricting to "true" severe COVID-19 (where oxygen requirement is due to COVID-19 rather than another condition(s)), and progression from oxygen use to IMV or death among COVID-19 patients. RESULTS: The analysis included 2125 individuals with respiratory failure (1608 cases [75.7%]; 99.2% of vaccinees received mRNA vaccines). During Delta, 2 doses provided high protection for up to 6 months (oxygen requirement: 95.2% [95% CI:88.7-98.0%] [restricted to "true" severe COVID-19: 95.5% {89.3-98.1%}]; IMV: 99.6% [97.3-99.9%]; fatal: 98.6% [92.3-99.7%]). During Omicron, 3 doses provided high protection for up to 6 months (oxygen requirement: 85.5% [68.8-93.3%] ["true" severe COVID-19: 88.1% {73.6-94.7%}]; IMV: 97.9% [85.9-99.7%]; fatal: 99.6% [95.2-99.97]). There was a trend towards higher VE for more severe and specific outcomes. CONCLUSION: Multiple outcomes pointed towards high protection of 2 doses during Delta and 3 doses during Omicron. These results demonstrate the importance of using severe and specific outcomes to accurately measure VE against severe COVID-19, as recommended in WHO guidance in settings of intense transmission as seen during Omicron

Combined Instruction in Each Subject Area in Education for Intellectual Disabilities Handling of Content and Evaluation of Learning in Each Subject Area Consideration of Measures Focusing on

知的障害のある児童生徒に対する教育を行う特別支援学校で実施されてきた，各教科等を合わせた指導において各教科等の内容の取扱いや学習評価に着目した方策の検討を行うため，合わせた指導の編成について調査を行った。また，筆者が所属する特別支援学校の教員の授業づくり等に関するアンケートの結果からは，具体的に指導内容を設定することの必要性を理解していても，合わせた指導のねらいを明確化することやねらいに沿った単元を計画することが難しいために，実際の授業では，具体的に指導内容を設定して指導をすることに難しさがあることが明らかになった。調査した合わせた指導の編成や所属校の教員の課題やニーズを踏まえて，対象児童生徒の主に取り扱う各教科の設定や主に展開される教科の評価を行うことができる「授業構想シート」と児童生徒一人一人の各教科等の指導内容の確認をすることができる「指導内容確認表」の作成を行った。In order to create a strategy focusing on the handling of the content of each subject and the evaluation of combined instruction in each subject area of specialneeds schools that provide education for students with intellectual disabilities, a survey of the organization of combined instruction in each subject area was conducted. Based on the organization of the combined instruction in each subject area and the issues and needs of the teachers in their schools, we prepared a lesson concept sheet that enables the setting of each subject to be mainly handled by the target students and the evaluation of the subjects to be mainly developed, and a confirmation chart of the content of instruction that enables the confirmation of the content of each subject and other instruction for each student