Contribution of Lung Fibroblast Migration in the Fibrotic Process of Airway Remodeling in Asthma

ABSTRACTBackgroundThe fibrotic process in airway remodeling of asthma may be characterized by an exaggerated deposition of extracellular matrix (ECM) components such as fibronectin and type I, III and IV collagen. In the present study, we established airway remodeling model mice and examined the mechanism of fibrotic change by measuring chemotactic activity of lung fibroblasts and quantifying collagen content in lung tissues.MethodsAirway remodeling model mice were made by ovalbumin (OA) sensitization and inhalation. Bronchoalveolar lavage (BAL) and bronchial biopsy were performed. Cell migration was assessed by the Boyden's chamber technique. The collagen content of lung tissue was measured using ELISA.ResultsThe chemotactic activity in lung fibroblasts toward the mouse BAL fluid (BALF) was significantly increased in OA-inhaled mice. Total soluble collagen content was significantly increased in OA-inhaled mice. We observed markedly increased collagen deposition around the airway wall in OA-inhaled mice, which was not shown in saline-inhaled mice. Furthermore, fibronectin in the BALF of OA-inhaled mice was significantly higher than that in the control mice.ConclusionsThe total soluble collagen content increased during the fibrotic change of airway remodeling in asthma. Furthermore, migration of fibroblasts may play a key role in this remodeling process, and fibronectin and type I and IV collagen seem to be chemotactic factors for the fibroblasts

Mammutprojekt Verkehrswende und aktuelle verkehrspolitische Fragen

Der Verkehrssektor muss seinen Beitrag zum Klimaschutz leisten. So wichtig der Umstieg auf elektrische Antriebe auf der Basis Erneuerbarer Energien auch ist: es geht nicht ohne einen Wandel des Verkehrsverhaltens und eine weitgehende Veränderung des Rechtsrahmens. Danach sieht es derzeit nicht aus, daher ist es nötig, die überfälligen Veränderungen probeweise und örtlich sowie zeitlich begrenzt zu versuchen

How should cardiac xenotransplantation be initiated in Japan?

The version of record of this article, first published in Surgery Today, is available online at Publisher’s website: https://doi.org/10.1007/s00595-024-02861-7.The world's first clinical cardiac xenotransplantation, using a genetically engineered pig heart with 10 gene modifications, prolonged the life of a 57-year-old man with no other life-saving options, by 60 days. It is foreseeable that xenotransplantation will be introduced in clinical practice in the United States. However, little clinical or regulatory progress has been made in the field of xenotransplantation in Japan in recent years. Japan seems to be heading toward a "device lag", and the over-importation of medical devices and technology in the medical field is becoming problematic. In this review, we discuss the concept of pig-heart xenotransplantation, including the pathobiological aspects related to immune rejection, coagulation dysregulation, and detrimental heart overgrowth, as well as genetic modification strategies in pigs to prevent or minimize these problems. Moreover, we summarize the necessity for and current status of xenotransplantation worldwide, and future prospects in Japan, with the aim of initiating xenotransplantation in Japan using genetically modified pigs without a global delay. It is imperative that this study prompts the initiation of preclinical xenotransplantation research using non-human primates and leads to clinical studies

The foremost and greatest barrier to end-stage heart failure treatment: the impact of caregiver shortage

The version of record of this article, first published in Journal of Artificial Organs, is available online at Publisher’s website: https://doi.org/0.1007/s10047-024-01463-x.We examined the number of patients abandoning cardiac replacement therapy due to the inability to secure a designated caregiver. At Osaka University Hospital Heart Center, when we receive a consultation for a patient with severe heart failure from another hospital, a heart failure team makes a visit to the referring hospital as soon as possible. We retrospectively analyzed this hospital-visit database. We received 199 severe heart failure consultations from 2016–2023. Issues identified during hospital visits included age ≥ 65 years (8%), inability to confirm the patient’s intention (8.5%), and explicit refusal of therapy (2.5%). Medical problems included multiple organ failure (18.1%), obesity (13.1%), diabetes (9.5%), malignancy (5.5%), chronic dialysis (1.0%), and other systemic diseases (12.6%). Adherence problems included poor medication compliance (3.5%), history of heavy drinking (2.5%), and smoking (2.0%). Social problems included inadequate family support in 16.1% of patients. Of the 199 patients, 95 (48.0%) proceeded to a heart transplant and LVAD indication review meeting at Osaka University Hospital. The remaining 104 patients (52.0%) did not proceed to the meeting. Reasons included improvement of heart failure with conservative treatment in 37 cases (35.6%), death before discussion in 21 cases (20.2%), medical contraindications in 18 cases (18.3%), lack of caregivers in 18 cases (18.3%; 9.5% of 199 cases), and patient refusal in 5 cases (4.8%). Approximately 10% of patients consulted at Osaka University Hospital Heart Center for severe heart failure abandoned cardiac replacement therapy due to the lack of caregivers

Soft-templated synthesis of mesoporous nickel oxide using poly(styrene-block-acrylic acid-block-ethylene glycol) block copolymers

In this work, we report the soft-templated preparation of mesoporous nickel oxide using an asymmetric poly(styrene-block-acrylic acid-block-ethylene glycol) (PS-b-PAA-b-PEG) triblock copolymer. This block copolymer forms a micelle consisting of a PS core, a PAA shell and a PEG corona in aqueous solutions, which can serve as a soft template. Specifically, the PS block forms the core of the micelles on the basis of its lower solubility in water. The anionic PAA block interacts with the cationic Ni ions present in the solution to generate the shell. The PEG block forms the corona of the micelles and stabilizes the micelles by preventing secondary aggregation through steric repulsion between the PEG chains. In terms of textural characteristics, the as-synthesized mesoporous NiO exhibits a large average pore size of 35 nm with large specific surface area and pore volume of 97.0 m g and 0.411 cm g, respectively. It is expected that the proposed soft-templated strategy can be expanded to other metal oxides/sulfides in the future for potential applications in gas sensors, catalysis, energy storage and conversion, optoelectronics, and biomedical applications

Functional characterization of the regulators of calcineurin in Candida glabrata

The serine-threonine-specific protein phosphatase calcineurin is a key mediator of various stress responses in fungi. Herein, we characterized functions of the endogenous regulators of calcineurin (RCNs), Rcn1 and Rcn2, in the pathogenic fungus Candida glabrata. Rcn1 exerted both inhibitory and stimulatory effects on calcineurin signaling, but Rcn2 displayed only inhibitory activity. Phenotypic analyses of C. glabrata strains lacking either RCNs, calcineurin, or both revealed that calcineurin requires Rcn1, but not Rcn2, for antifungal tolerance in C. glabrata

建学の精神の徹底を図る初年次教育の実践と課題 ―ホスピタリティ概論の分析から―

本研究は、2017年度から始まった本学の初年次教育を定着させるとともに、新入生が大学での教育を理解し、建学の精神に代表される理念やディプロマポリシーを自分のものとして捉え、その実現に向けた主体的な学修の基盤を構築するという初年次教育の目標の達成を図ることにある。このためには、彼らの特性をとらえるとともに、彼らが初年次教育をどのように捉え、理解したかを把握しなければならない。そこで初年次教育の科目の一つとして開設された「ホスピタリティ概論」を活用して、全受講生を対象とした2つの調査を3年間実施した。1つ目の調査は入学当初の学生像をとらえ授業展開に生かすために学生の特徴を把握するものであり、第1回目の授業で実施された。2つ目の調査は授業内容の理解度を評価するものであり、第10回目に実施された。これらの回答を年度と学科毎に集計、分析した。その結果、次のことが明らかになった。①オープンキャンパスへの参加や進学希望状況などの本学入学に至る経緯が学科によって異なること、そして、入学当初には心身に不安を抱いている学生が、どの学科にも相当数存在すること。3年間の調査によって各学科の学生の特色が明らかになり、学科毎の適切な学修支援方策の作成に向けた示唆が得られたこと。②この講義を受けて、建学の精神であるホスピタリティの獲得に大学が力を入れており、その実現が求められていると多くの学生が認識していること、及び、本科目の重点目標である多様性の理解力の育成につながる他学科の学生とのコミュニケーションの機会に意義を見出していること等から、授業の目標達成に向けた順調な歩みが見られること。これらの結果及び他の科目の報告から、初年次教育が定着しつつあること、そして、その目標達成に向けた歩みが順調であると判断した。ただ、更なる充実のための課題も浮かび上がっている

The glycosylphosphatidylinositol-linked aspartyl protease Yps1 is transcriptionally regulated by the calcineurin-Crz1 and Slt2 MAPK pathways in Candida glabrata.

In the pathogenic fungus Candida glabrata, the YPS1 gene, which encodes a glycosylphosphatidylinositol-linked aspartyl protease, is required for cell wall integrity and virulence. Although the expression of YPS1 has been studied in Saccharomyces cerevisiae, the transcriptional regulation of this gene in C. glabrata is not well understood. Here, we report that C. glabrata Yps1 is required for cell growth at elevated temperatures, and that the heat-induced expression of YPS1 is regulated predominantly by the calcineurin-Crz1 pathway and partially by the Slt2 MAPK pathway. Although a total of 11 YPS genes are present in the C. glabrata genome, the loss of transcriptional induction in a calcineurin mutant was observed only for YPS1. The results of a YPS1 promoter-lacZ reporter assay using a series of constructs with mutated promoter elements indicated that the transcription factor Crz1 binds to multiple sites in the promoter region of YPS1. To date, as none of the putative Crz1 targets in C. glabrata have been characterized using a Δcrz1 mutant, monitoring the expression of YPS1 represents an effective method for measuring the activity of the calcineurin-Crz1 signaling pathway in this fungus

VERTECS: 6U CubeSat Mission to Study Star-Formation History by Observation of Visible Extragalactic Background Light

We describe an astronomical 6U CubeSat mission VERTECS (Visible Extragalactic background RadiaTion Exploration by CubeSat). The scientific purpose of VERTECS is to reveal star-formation history of the universe by observation of the extragalactic background light (EBL) in visible wavelengths. Earlier observations by sounding rockets and infrared astronomical satellites have shown that the near-infrared EBL is several times brighter than the integrated light of known galaxies. As candidates for the excess light, first-generation stars in the early universe or low-redshift intra-halo light have been proposed, but it has not been concluded. Since these objects are expected to show different emission spectra in visible wavelengths, precise visible observation is important to reveal the origin of excess light. Since detection sensitivity of the EBL is determined by the product of telescope aperture and field of view, a small wide-field telescope system enables the EBL observation with high sensitivity. In VERTECS mission, we develop a 6U CubeSat equipped with a 3U size telescope optimized for observation of visible EBL. The telescope is composed of lens optics and a CMOS sensor of 3k times 3k array format, which is designed to observe the sky in four photometric bands in 400-800nm. The satellite bus is composed of on-board computer (OBC), electric power system (EPS), communication (COM), attitude determination and control system (ACDS), and thermal structure. Design of OBC and EPS is based on heritage of CubeSats developed at Kyushu Institute of Technology, but deployable solar array wings is added to EPS to supply sufficient power to the VERTECS subsystems. In COM system, S-band is used for command uplink and X-band is used for high-speed downlink of large-size images captured by the telescope. Since the EBL measurement need discrimination of the background light from discrete foreground stars, VERTECS requires 10 arcseconds pointing stability (1 sigma) over 1 minute exposure. In 2022, VERTECS was selected for JAXA-Small Satellite Rush Program (JAXA-SMASH Program), a new program that encourages universities, private companies and JAXA to collaborate to realize small satellite missions utilizing commercial small launch opportunities, and to diversify transportation services in Japan. We have been working on functionality and interface teast using Bread Board Model (BBM), and enviroonmental tests by using the satellite structure thermal model. Launch of the satellite is planned in FY2025. We aim at developing the satellite and obtaining scientific results much more quickly than recent large astronomical-satellite missions