Dispensabilities of Carbonic Anhydrase in Proteobacteria

Carbonic anhydrase (CA) (E.C. 4.2.1.1) is a ubiquitous enzyme catalysing interconversion between CO2 and bicarbonate. The irregular distribution of the phylogenetically distinct classes of CA in procaryotic genome suggests its complex evolutionary history in procaryotes. Genetic evidence regarding the dispensability of CA under high-CO2 air in some model organisms indicates that CA-deficient microorganisms can persist in the natural environment by choosing high-CO2 niches. In this study, we studied the distribution of CA in the genome of Proteobacteria. While a large majority of the genome-sequenced Proteobacteria retained a CA gene(s), intracellular bacterial genera such as Buchnera and Rickettsia contained CA-defective strains. Comparison between CA-retaining and CA- deficient genomes showed the absence of whole coding sequence in some strains and the presence of frameshifted coding sequence in other strains. The evidence suggests that CA is inactivated and lost in some proteobacteria during the course of evolution based on its dispensability

Dibutyryl cyclic adenosine monophosphate attenuates lung injury caused by cold preservation and ischemia-reperfusion

AbstractObjective: Dibutyryl adenosine 3`,5`cyclic monophosphate (db-cAMP) is a membrane-permeable analog of adenosine 3`,5`cyclic monophosphate (cAMP). We examined the effect of db-cAMP against lung injury caused by cold preservation and ischemia-reperfusion. Methods: Rats were divided into three groups (each n = 6) according to the presence or absence of db-cAMP in the preservative solution and cold ischemia (4° C for 15 hours). In the fresh group, the lung was flushed with the preservative solution and reperfusion was performed immediately. In the control group and the db-cAMP group, the lung was flushed either with the solution or with a combination of the solution plus db-cAMP, respectively, and preserved at 4° C for 15 hours. The lung was reperfused for 60 minutes in an ex vivo rat lung perfusion model. Results: The shunt ratios of the reperfused lung in the db-cAMP group were 4.0% ± 1.6% and 3.4% ± 1.2% 10 and 60 minutes, respectively, after the initiation of reperfusion, being as low as those in the fresh group and significantly lower than those in the control group (p < 0.01). The wet/dry weight ratio of the lung tissue after reperfusion was 5.99 ± 1.50 in the db-cAMP group, which was similar to that in the fresh group (5.45 ± 0.23) and significantly lower than that in the control group (14.20 ± 3.43) (p < 0.01). Electron microscopic examination showed less damage in the pulmonary arterial endothelium in the db-cAMP group. Conclusions: We conclude that db-cAMP attenuates the lung injury by cold preservation and ischemia-reperfusion, at least partly by protection of the vascular endothelium. (J Thorac Cardiovasc Surg 1997;114:635-42

Multiple inflammatory cytokine-productive ThyL-6 cell line established from a patient with thymic carcinoma

Thymic epithelial cells can produce many kinds of cytokines, and interleukin (IL)-6-producing thymic carcinoma cases have been reported. However, a cytokine-producing human thymic tumor cell line has not previously been established. In this paper, we report a novel, multiple inflammatory cytokine-productive cell line that was established from a patient with thymic carcinoma. This cell line, designated ThyL-6, positively expressed epithelial membrane antigen, cytokeratins, vimentin intermediate filament and CD5, although hematological markers were not present in the cells. Cytokine antibody array analysis showed that the cells secreted several cytokines including IL-1α, IL-6, IL-8, RANTES, soluble TNFα-receptor 1, VEGF and CTLA into the culture medium. The addition of ThyL-6-cultured supernatant supported the growth of human myeloma ILKM-3 cells, which require the presence of IL-6 in the culture medium for the maintenance of cell growth, suggesting that the secreted IL-6 from ThyL-6 cells was biologically active. Chromosome analysis demonstrated that ThyL-6 cells had complex karyotype anomalies, including der(16)t(1;16); the latter has been recognized in thymic squamous cell carcinoma and thymic sarcomatoid carcinoma cases, as well as in several other kinds of malignancies. Heterotransplantation of the cells into nude mice showed tumorigenesis with neutrophil infiltration and liquefactive necrosis. These findings suggest that ThyL-6 cells will provide us with a new experimental tool for investigating not only the pathogenesis, biological behavior, chromo-somal analysis and therapeutic reagents of human thymic carcinoma, but also for studying cytokine-chemokine network systems

Baseline Neutrophil-to-Lymphocyte Ratio and Glasgow Prognostic Score are Associated with Clinical Outcome in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma Treated with Nivolumab

Recurrent or metastatic head and neck squamous cell carcinoma (R/MHNSCC) has a poor prognosis. Although nivolumab is approved in Japan for treating R/MHNSCC, the response rate is low. Therefore, identifying pretreatment prognostic factors is necessary. This study assessed the utility of the neutrophil-to-lymphocyte ratio (NLR) and Glasgow Prognostic Score (GPS) as biomarkers of response to nivolumab. We retrospectively collected the data of 56 R/MHNSCC patients treated with nivolumab between May 2017 and December 2019. The Kaplan–Meier method and log-rank test were used to estimate overall survival (OS) and progression-free survival (PFS), and multivariate Cox hazard regression analysis was used to identify independent predictors of survival. Patients with a low pretreatment NLR had prolonged OS, and patients with a low pretreatment GPS had increased OS and PFS. A performance score (PS) of 0-1, development of immune-related adverse events, and GPS of 0-1 were significantly associated with OS in multivariate analysis. In summary, baseline pretreatment NLR and GPS are independently associated with OS in R/MHNSCC patients treated with nivolumab. Administration of nivolumab while maintaining the PS reflects a immune status of the host and leads to a good OS

Development of a glue-free bimorph mirror for use in vacuum chambers

PZT (lead zirconate titanate)-glued bimorph deformable mirrors are widely used in hard X-ray regimes; however, they have not yet been used in soft X-ray regimes because they are less compatible for usage under high vacuum. In this study, we developed a glue-free bimorph deformable mirror, in which silver nano-particles were employed to bond PZT actuators to mirror substrates. Under an appropriate bonding condition, the bonding layer was confirmed to be uniform and the mirror's bending characteristics were demonstrated to be sufficiently stable; its gas emission rate was also shown to be acceptable. Piezo responses before and after additional heating at 200 °C showed the thermal stability of its bonding and bending properties.Yoshio Ichii, Hiromi Okada, Hiroki Nakamori, Akihiko Ueda, Hiroyuki Yamaguchi, Satoshi Matsuyama, and Kazuto Yamauchi, "Development of a glue-free bimorph mirror for use in vacuum chambers", Review of Scientific Instruments 90, 021702 (2019), https://doi.org/10.1063/1.5066105

Physiological and Pathological Mitochondrial Clearance Is Related to Pectoralis Major Muscle Pathogenesis in Broilers With Wooden Breast Syndrome

Wooden breast syndrome (WB) constitutes an emerging myopathy in the pectoralis major muscle (PM) of broiler chickens, characterized by myofiber hypertrophy and degeneration along with severe fibrosis. WB pathogenesis has been considered to involve hypoxia induced by rapid growth of the PM. In this study, we focused on mitochondrial morphology and dynamics in the myofibers, as these organelles are sensitive to damage by hypoxia, and examined the effects on WB pathogenesis. Specifically, the PMs of a flock of 35 broilers at 50 days of age were evaluated. First, the severity of disease in each bird was determined by measuring histopathological indices including the fibrotic area (FA) in the muscle and circularity of myofibers (CM). These values were 29.4 ± 9.6% and 0.70 ± 0.042, respectively, showing variety among the flock. Myofiber vacuolization was observed in all birds including numerous small- or large-rimmed vacuoles, with the former consisting of ultrastructurally autophagosome-like vacuoles engulfing degenerated mitochondria. The large-rimmed vacuoles frequently occurred in the PMs with more severe FA and CM, indicating a relationship between altered autophagy/mitophagy and WB severity. Next, the expression levels of hypoxia-adaptive and mitochondrial dynamics-related genes were analyzed, and their correlations with the histopathological indices were examined. The histopathological indices were negatively correlated with the expression of vascular endothelial growth factor A (VEGFA), indicating that less angiogenesis owing to weakened hypoxia-inducible factor signaling induces more severe WB pathology. In addition, the observed negative correlation with mitochondrial dynamics-related genes implied that WB pathology deteriorates concomitant with reduced mitochondrial dynamics. Furthermore, the expression of mitochondrial dynamics-related genes showed strong positive correlation with that of VEGFA and autophagy-/mitophagy-related genes. These results revealed that the PMs of broilers possess the mechanism of physiological clearance of mitochondria damaged by the hypoxia resulting from the continuous mitochondrial dynamics and autophagy/mitophagy accompanying rapid PM growth. In turn, the altered mitochondrial clearance induced by chronic hypoxia and the accumulation of damaged mitochondria likely underly the severe pathological features of WB.ArticleFrontiers in Pharmacology.11:579(2020)journal articl

Creating Classes for Developing the Concept of Functions : A System of Learning Activities for Drawing out Four Qualities Tied to Nurturing the Concept of Functions

本研究は，数・量・図形的要素を見出し，どのような関係があるのかを考え，そこにきまりを発見していく力を育成するために以下の研究を進めた。昨年度は，函数観念の育成につながる授業の中で引き出したい４つの姿である，①事象の中に数・量・図形的要素を見つけようとする姿，②どのような関係かを考えていこうとする姿，③関係の中にある法則を見つけようとする姿，④事象を関係で見ていこうとする姿を発達段階ごとに設定し，その４つの姿を引き出すことを目的とした学習活動を仕組む授業実践を積み重ねた。さらに，本年度は，「関数の考えの指導」の関数の考えの背景となる「物事を動的に見ようとする態度」に焦点をあて，４つの姿を引き出すこととする。それらの取り組みを小学校と中学校で統一して取り組むことで「中一ギャップ」や算数・数学への円滑な移行ができると考えた。その結果，単元の事前と事後，昨年と今年とでは４つの姿をについて，どの項目についても肯定的な回答であった。また，教師が意図的に関数の考えを授業の中で取り扱っていくことが，子どもに「関数の観念」を育んでいく上で効果的であり，小・中学校で統一した指導も可能であることが分かった。This study was conducted, as a means of nurturing the ability to discover set facts when seeking out numerical, volumetric, and graphical elements in pondering relationships. Last year, four of figure you want a drawer in the class, which leads to the development of the function concept has been pulled out. This year, the focus was placed on “attitudes for seeing things dynamically”, as a precursor to thinking about functions, and the instruction thereof. It was felt that unifying these efforts in elementary and junior high schools would relieve the “first-year gap”. The result of these efforts was a positive response to all four qualities in both years, before and after the teaching units. In addition, teachers’ deliberate treatment of the idea of functions in classrooms was effective in engendering the “concept of functions” in children, showing that it is possible to have a unified way of teaching in elementary and junior high schools