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Naoyuki Akashi,1 Tomio Umemoto,1 Hodaka Yamada,2 Takayuki Fujiwara,3 Kei Yamamoto,1 Yousuke Taniguchi,1 Kenichi Sakakura,1 Hiroshi Wada,1 Shin-ichi Momomura,1 Hideo Fujita1 1Division of Cardiovascular Medicine, Jichi Medical University Saitama Medical Center, Saitama, Japan; 2Division of Endocrinology and Metabolism, Jichi Medical University Saitama Medical Center, Saitama, Japan; 3Department of Cardiovascular Medicine, The University of Tokyo Hospital, Tokyo, JapanCorrespondence: Tomio Umemoto, Division of Cardiovascular Medicine, Jichi Medical University Saitama Medical Center, 1-847 Amanuma-cho, Omiya-ku, Saitama, 330-8503, Japan, Tel +81-48-647-2111, Fax +81-48-648-5188, Email to-ume@omiya.jichi.ac.jpPurpose: Dipeptidyl peptidase-4 (DPP-4) inhibitors increase endothelial progenitor cells (EPCs) in peripheral blood circulation. However, the underlying mechanisms and effects on vascular endothelial function remain unclear. We evaluated whether the DPP-4 inhibitor teneligliptin increases circulating EPCs by inhibiting stromal-derived factor-1α (SDF-1α) and improves flow-mediated vascular dilatation (FMD) in type 2 diabetes mellitus patients with acute coronary syndrome (ACS) or its risk factors.Patients and Methods: This single-center, open-label, prospective, randomized controlled trial evaluated 17 patients (hemoglobin A1c ≤ 7.5% and peak creatinine phosphokinase < 2000 IU/mL) with ACS or a history of ACS or multiple cardiovascular risk factors. Metabolic variables of glucose and lipids, circulating EPCs, plasma DPP-4 activity, and SDF-1α levels, and FMD were evaluated at baseline and 28 ± 4 weeks after enrollment. Patients were randomly assigned to either the teneligliptin (n = 8) or control (n = 9) groups.Results: The DPP-4 activity (∆− 509.5 ± 105.7 vs ∆32.8 ± 53.4 μU/mL) and SDF-1α levels (∆− 695.6 ± 443.2 vs ∆11.1 ± 193.7 pg/mL) were significantly decreased after 28 weeks in the teneligliptin group than those in the control group. The number of EPCs showed an increasing trend in the teneligliptin treated group; albeit this did not reach statistical significance. Glucose and lipid levels were not significantly different between the groups before and after 28 weeks. However, FMD was significantly improved in the teneligliptin group when compared to the control group (∆3.8% ± 2.1% vs ∆− 0.3% ± 2.9%, P=0.006).Conclusion: Teneligliptin improved FMD through a mechanism other than increasing the number of circulating EPCs.Keywords: endothelial progenitor cell, teneligliptin, DPP-4 inhibitor, flow-mediated dilation, type 2 diabetes mellitus

With the widespread use of implantable left ventricular assist device (LVAD), right ventricular failure (RVF) has become a serious problem that becomes apparent several weeks or later after LVAD implantation. However, there are no marked preoperative signs of RVF. This is called late-onset RVF and is currently a major problem leading to long-term complications following implantable LVAD use. Pathogenically, this could be the result of left ventricular suction by LVAD that causes the septum shift to the left ventricular side. This causes a change in morphology of the right ventricle, resulting in impaired right ventricular function. Aortic insufficiency and ventricular arrhythmia, which are also important as long-term complications after LVAD implantation, are considered to be closely involved in the onset and progression of RVF. Once late-onset RVF develops, exercise capacity declines and inotrope administration may be required. Late-onset RVF was also reported to be significantly associated with increased mortality. Several predictors of RVF have been proposed such as preoperative left ventricular diastolic dimension64 mm, tricuspid valve annulus diameter ≥41 mm, and so on. However, some reports identified no predictors. The basic treatment strategy for late-onset RVF is to optimize volume status by administering diuretics and ensuring inotrope as needed. β-blockers and antiarrhythmic agents often need to be reduced in terms of dosage or even discontinued because these might reduce right ventricular function. Although their efficacy is unclear, pulmonary vasodilators may be used to reduce right ventricular afterload. It is better to decrease the rotation speed of LVAD to minimize the displacement of the septum; however, this is often difficult because the required flow rate cannot be secured. Progress in the prevention and management of late-onset RVF is required because the number of patients who require longer-term LVAD support will increase with the spread of LVAD use as destination therapy.

Lung transplantation (LT) is the only option for patients with pulmonary arterial hypertension (PAH) refractory to maximal medical therapy. However, some patients referred for LT could survive without LT, and its determinants remain unclear. This study aimed to elucidate prognostic factors of severe PAH at the referral time. We retrospectively analyzed 34 patients referred for LT evaluation. The primary outcome was a composite of death or LT. Over a median follow-up period of 2.56 years, eight patients received LT and eight died. Compared with LT-free survival group, pulmonary arterial systolic pressure (PASP) was higher (p = 0.042), and the ratio of tricuspid annular plane systolic excursion (TAPSE) to PASP (TAPSE/PASP) was lower (p = 0.01) in LT or death group. In receiver operating characteristic analysis, the area under the curve was 0.759 (95% confidence interval 0.589–0.929) for TAPSE/PASP to predict primary outcome, and the optimal cut-off value was 0.30 mm/mmHg (sensitivity 0.875 and specificity 0.667). In a multivariate analysis, TAPSE/PASP was independently associated with death or LT. Kaplan–Meier analysis showed a better LT-free survival in patients with TAPSE/PASP ≧0.30 mm/mmHg than in those with p = 0.001). Low-level TAPSE/PASP could be a poor prognostic factor in PAH patients referred for LT evaluation.

Protein C (PC) is a plasma anticoagulant encoded byPROC; mutation in bothPROCalleles results in neonatal purpura fulminans—a fatal systemic thrombotic disorder. In the present study, we aimed to develop a genome editing treatment to cure congenital PC deficiency. First, we generated an engineered activated PC to insert a self-cleaving peptide sequence between light and heavy chains. The engineered PC could be released in its activated form and significantly prolonged the plasma coagulation time independent of the cofactor activity of protein Sin vitro. The adeno-associated virus (AAV) vector-mediated expression of the engineered PC, but not wild-type PC, prolonged coagulation time owing to the inhibition of activated coagulation factor V in a dose-dependent manner and abolished pathological thrombus formationin vivoin C57BL/6 mice. The insertion ofEGFPsequence conjugated with self-cleaving peptide sequence atAlblocus via neonatalin vivogenome editing using AAV vector resulted in the expression of EGFP in 7% of liver cells, mainly via homology-directed repair, in mice. Finally, we succeeded in improving the survival of PC-deficient mice by expressing the engineered PC via neonatal genome editingin vivo. These results suggest that the expression of the engineered PC via neonatal genome editing is a potential cure for severe congenital PC deficiency.One Sentence SummaryEctopic expression of an engineered protein C via genome editing cures protein C deficiency in mice.

Aquaculture of marine macroalgae (i.e. seaweeds) such as the kelp Undaria pinnatifida is expected to contribute to future food and biomass production. Although macroalgal survival, biomass, and morphology are strongly affected by the density of individual plants in natural environments, little is known about the cultivation density (individuals per 1 m of cultivation rope) of macroalgae required to optimize aquaculture production, commercial profit (sales – labor expenses for processing), and quality as food. The present study examined the effect of increasing the cultivation density of U. pinnatifida from 10 to 200 individuals m-1 on survival rate, biomass production, profit, and morphological features related to quality as food. Survival rate was almost 100% in all treatments, indicating self-thinning did not occur. Biomass production increased with increasing density, suggesting that the maximum density possible is in excess of 200 individuals m-1. However, although profit rose with increasing density from 10 to 120 individuals m-1, it did not rise further if density was further increased. Moreover, some morphological features related to quality increased or decreased with increasing density. On balance, these results suggest that 80-120 individuals m-1 is an appropriate density range to optimize production of this species in terms of both profit and quality as food. However, only 10-30 individuals m-1 was the density best suited to enhance production of the sporophyll form, which is known to be a nutritious food both for humans and sea urchins.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease with obstructed airflow and frequently causes secondary mild-moderate pulmonary hypertension (PH). However, a low proportion (1%-5%) of COPD patients develop severe therapy-resistant PH, and it is crucial to determine whether the patient has another disease capable of causing severe PH, including pulmonary arterial hypertension.Here, we describe a case of a 71-year-old male with COPD complicated by severe PH and right heart failure. He had a history of heavy smoking and developed progressive hypoxemia on exertion. He had severe airflow limitation (forced expiratory volume % in one second, FEV 1.0% = 42.8%) with a markedly reduced diffusing capacity of the lung (predicted diffusion capacity of carbon monoxide, %DLCO = 29%), and high-resolution computed tomography (CT) demonstrated significant lung parenchymal abnormalities such as diffuse interlobular septal thickening, ground-glass opacities, and enlarged mediastinal lymph nodes. He was diagnosed with group 3 PH caused by COPD but resistant to the treatment of COPD, diuretics, and oxygen therapy. Pathohistological analysis of autopsy specimens revealed the coexistence of interstitial fibrosis and partial occlusion of the small intrapulmonary veins, which led to a conclusive diagnosis of pulmonary veno-occlusive disease (PVOD).Because of its rarity and similarity with idiopathic pulmonary arterial hypertension, PVOD is difficult to diagnose antemortem and has a poor prognosis. High-resolution CT findings (septal thickening, ground glass, and enlarged lymph nodes) and severely reduced DLCO should be carefully evaluated for the early detection and treatment of PVOD in COPD patients with severe PH.

Sexual reproduction is widespread in eukaryotes; however, only asexual reproduction has been observed in unicellular red algae, including

Sexual reproduction is widespread in eukaryotes; however, only asexual reproduction has been observed in unicellular red algae, including Galdieria , which branched early in Archaeplastida. Galdieria possesses a small genome; it is polyextremophile, grows either photoautotrophically, mixotrophically, or heterotrophically, and is being developed as an industrial source of vitamins and pigments because of its high biomass productivity. Here, we show that Galdieria exhibits a sexual life cycle, alternating between cell-walled diploid and cell wall–less haploid, and that both phases can proliferate asexually. The haploid can move over surfaces and undergo self-diploidization or generate heterozygous diploids through mating. Further, we prepared the whole genome and a comparative transcriptome dataset between the diploid and haploid and developed genetic tools for the stable gene expression, gene disruption, and selectable marker recycling system using the cell wall–less haploid. The BELL/KNOX and MADS-box transcription factors, which function in haploid-to-diploid transition and development in plants, are specifically expressed in the haploid and diploid, respectively, and are involved in the haploid-to-diploid transition in Galdieria , providing information on the missing link of the sexual life cycle evolution in Archaeplastida. Four actin genes are differently involved in motility of the haploid and cytokinesis in the diploid, both of which are myosin independent and likely reflect ancestral roles of actin. We have also generated photosynthesis-deficient mutants, such as blue-colored cells, which were depleted in chlorophyll and carotenoids, for industrial pigment production. These features of Galdieria facilitate the understanding of the evolution of algae and plants and the industrial use of microalgae.

Several eukaryotic cell lineages proliferate by multiple fission cell cycles, during which cells grow to manyfold of their original size, then undergo several rounds of cell division without intervening growth. A previous study on volvocine green algae, including both unicellular and multicellular (colonial) species, showed a correlation between the minimum number of successive cell divisions without intervening cellular growth, and the threshold cell size for commitment to the first round of successive cell divisions: two times the average newly born daughter cell volume for unicellular Chlamydomonas reinhardtii, four times for four-celled Tetrabaena socialis, in which each cell in the colony produces a daughter colony by two successive cell divisions, and eight times for the eight-celled Gonium pectorale, in which each cell produces a daughter colony by three successive cell divisions. To assess whether this phenomenon is also applicable to other lineages, we have characterized cyanidialean red algae, namely, Cyanidioschyzon merolae, which proliferates by binary fission, as well as Cyanidium caldarium and Galdieria sulphuraria, which form up to four and 32 daughter cells (autospores), respectively, in a mother cell before hatching out. The result shows that there is also a correlation between the number of successive cell divisions and the threshold cell size for cell division or the first round of the successive cell divisions. In both C. merolae and C. caldarium, the cell size checkpoint for cell division(s) exists in the G1-phase, as previously shown in volvocine green algae. When C. merolae cells were arrested in the G1-phase and abnormally enlarged by conditional depletion of CDKA, the cells underwent two or more successive cell divisions without intervening cellular growth after recovery of CDKA, similarly to C. caldarium and G. sulphuraria. These results suggest that the threshold size for cell division is a major factor in determining the number of successive cell divisions and that evolutionary changes in the mechanism of cell size monitoring resulted in a variation of multiple fission cell cycle in eukaryotic algae.

Free-living filamentous thalli derived from an Analipus japonicus erect thallus were established in laboratory culture. The filamentous thalli were composed of slender filaments and densely pigmented oval or sub-oval cell masses. Temperature (5–20 °C) and irradiance (25–200 μmol photons m−2 s−1) effects on formation and growth of the thalli from three explant groups (isolated filaments, small cell masses, and large cell masses) were investigated for 15 days. These explants survived over the examined range. The isolated filaments had a high ability to form the thalli, and the isolated and new filaments formed filaments and cell masses. Meanwhile, the isolated and new cell masses formed only filaments, and their ability to grow and form the thalli decreased as they grew in size. Optimum culture conditions for formation and growth of the thalli from the isolated filaments, and the two cell mass growths were 15–20 °C and 100–200 μmol photons m−2 s−1. To produce erect thalli, the filamentous thalli were cultured on seedling threads for 6 weeks at 15 °C, 60 μmol photons m−2 s−1 and 20 cm s−1 water flow velocity. Erect axis density increased with increasing coverage of the filamentous thalli, and their cell masses (primordia of erect thallus holdfast) with mean area of about 140 × 103 μm2 began to produce erect axes. After 4 months of field cultivation, they grew into full-grown erect thalli of about 20 cm long. These findings show that the free-living filamentous thalli were applicable for stable seedling production of A. japonicus to be used in aquaculture.

To achieve efficient multi-port model order reduction, a multi-port Cauer ladder network (CLN) method is formulated that directly yields resistance and inductance matrices that constitute the network elements in the matrix Cauer form. The eddy-current field driven by multiple power sources is accurately reconstructed using a small number of network elements. The matrix Cauer form achieves faster convergence of the transfer function than a single-port CLN method and almost the same convergence as a block Padé via Lanczos (PVL) method.

The cost and/or cost-effectiveness for inpatient management according to the gender of attending physicians remain to be elucidated.Hospitalization costs were extracted from the Diagnosis Procedure Combination (DPC) -based payment system. Using a dataset of 7,457 hospitalized patients with cardiovascular diseases in our hospital from 2012 to 2018, we compared the actual cost of inpatient management by female cardiologists with that by male cardiologists. Next, we estimated the cost-effectiveness of inpatient management according to the gender of the attending cardiologist. The cost of initial hospitalization per patient was similar between the patients treated by a female or male middle-grade cardiologist ($17,527 ± 14,158, versus $17,358 ± 15,183, P = 0.69). As an analysis on cost-effectiveness, the incremental cost of hospitalization managed by male middle-grade cardiologists was $67 per patient as compared with female middle-grade cardiologists. Concordantly, evaluation of the incremental cost-effectiveness ratio per quality-adjusted life year gained showed that the inpatient management by female cardiologists was dominant over that by male cardiologists.Inpatient management by female cardiologists was more cost-effective as compared with that by male cardiologists. Physician gender might have a considerable effect on medical economics.

The unicellular alga Cyanidioschyzon merolae has a simple cellular structure; each cell has one nucleus, one mitochondrion, one chloroplast and one peroxisome. This simplicity offers unique advantages for investigating organellar proliferation and the cell cycle. Here, we describe CZON-cutter, an engineered clustered, regularly interspaced, short palindromic repeats (CRISPR)/CRISPR-associated nuclease 9 (Cas9) system for simultaneous genome editing and organellar visualization. We engineered a C. merolae strain expressing a nuclear-localized Cas9–Venus nuclease for targeted editing of any locus defined by a single-guide RNA (sgRNA). We then successfully edited the algal genome and visualized the mitochondrion and peroxisome in transformants using fluorescent protein reporters with different excitation wavelengths. Fluorescent protein labeling of organelles in living transformants allows us to validate phenotypes associated with organellar proliferation and the cell cycle, even when the edited gene is essential. Combined with the exceptional biological features of C. merolae, CZON-cutter will be instrumental for investigating cellular and organellar division in a high-throughput manner. This article has an associated First Person interview with the first author of the paper.

Variant types and sites in a single gene could influence the age of onset, severity, and pattern of affected organs of the genetic disease, such as in Marfan syndrome (MFS)-causing FBN1, and understanding the genotype-phenotype relationship could aid in determining the treatment strategy. In contrast, completely distinct system and/or organ diseases induced by 1 gene mutation have been rarely reported. Transforming growth factor-β (TGF-β) type I receptor-encoding TGFBR1 is such a gene, causing Loeys-Dietz syndrome (LDS) closely related to MFS, and also multiple self-healing squamous epithelioma (MSSE) without clinical overlap. The detailed mechanisms underlying this effect, however, remain elusive. We recently reported the significance of 2 distinct intronic variants (c.973+1G>A and c.806-2A>C) of TGFBR1, which were both predicted to mediate in-frame exon 5 skipping but caused LDS and MSSE, respectively. On ex vivo minigene splicing assay analysis we demonstrated that 2 different cryptic splice sites were activated, and in-frame and out-of-frame transcripts were produced in LDS and MSSE, respectively, supporting the previously proposed but not yet approved mechanism that loss-of-function and haploinsufficiency-causing variants in serine/threonine kinase domains induce LDS and MSSE, respectively. In this review, we briefly summarize the recent findings and unresolved problems for the pathogenesis of LDS, including the TGF-β signaling paradox: most variants have been verified or predicted to be loss of function in vitro, but these variants enhanced TGF-β signaling in vivo.

The Cauer ladder network (CLN) method provides an efficient representation of eddy-current fields. This paper proposes a reformulation of the CLN method that considers expansion points using the magnetic/current vector potential. To cover a wide range of frequencies, the expansion point may be changed at a later stage of the network. Only a few stages of the ladder network are required for the eddy-current field to be reconstructed accurately around the target frequency using the expansion points.

This study is a prospective evaluation of the effectiveness of cardiac rehabilitation (CR) in terms of clinical outcomes for small abdominal aortic aneurysms (AAA) that were previously reported in a retrospective cohort study. We conducted a prospective non-randomized trial on patients with small AAA (N = 40; mean age 75.0 ± 6.6 years). Patients were enrolled into one of two groups, rehabilitation (CR) or non-rehabilitation (non-CR) group. Only CR group participated in a supervised-CR program including bicycle ergometer for 150 days. The AAA expansion rate and the risk of AAA repair were compared between two groups. We also researched the relationship between AAA expansion rate and body composition, blood IL-6 and TGFβ1 levels. The CR (N = 15) and non-CR groups (N = 25) were comparable in terms their baseline data. The CR group had a significantly smaller change in the maximal AAA size (− 1.3 ± 2.4 mm/years) compared to the non-CR group (2.0 ± 3.6 mm/years) (p

Here, we report the development of a novel photoactive biomolecular nanoarchitecture based on the genetically engineered extremophilic photosystem I (PSI) biophotocatalyst interfaced with a single layer graphene via pyrene-nitrilotriacetic acid self-assembled monolayer (SAM). For the oriented and stable immobilization of the PSI biophotocatalyst, an His6-tag was genetically engineered at the N-terminus of the stromal PsaD subunit of PSI, allowing for the preferential binding of this photoactive complex with its reducing side towards the graphene monolayer. This approach yielded a novel robust and ordered nanoarchitecture designed to generate an efficient direct electron transfer pathway between graphene, the metal redox center in the organic SAM and the photo-oxidized PSI biocatalyst. The nanosystem yielded an overall current output of 16.5 µA·cm−2 for the nickel- and 17.3 µA·cm−2 for the cobalt-based nanoassemblies, and was stable for at least 1 h of continuous standard illumination. The novel green nanosystem described in this work carries the high potential for future applications due to its robustness, highly ordered and simple architecture characterized by the high biophotocatalyst loading as well as simplicity of manufacturing.

Percutaneous coronary intervention (PCI) is sometimes considered as an alternative therapeutic strategy to surgical revascularization in patients with coronary artery disease (CAD) and reduced left ventricular ejection fraction (LVEF). However, the types or conditions of patients that receive the clinical benefit of left ventricular reverse remodelling (LVRR) remain unknown. The purpose of this study was to investigate the determinants of LVRR following PCI in CAD patients with reduced LVEF. From 4394 consecutive patients who underwent PCI, a total of 286 patients with reduced LV systolic function (LVEF

Several eukaryotic cell lineages proliferate by multiple fission cell cycles, during which cells grow to manyfold of their original size, then undergo several rounds of cell division without intervening growth. A previous study on volvocine green algae, including both unicellular and multicellular (colonial) species, showed a correlation between the minimum number of successive cell divisions without intervening cellular growth, and the threshold cell size for commitment to the first round of successive cell divisions: two times the average newly born daughter cell volume for unicellular Chlamydomonas reinhardtii, four times for four-celled Tetrabaena socialis, in which each cell in the colony produces a daughter colony by two successive cell divisions, and eight times for the eight-celled Gonium pectorale, in which each cell produces a daughter colony by three successive cell divisions. To assess whether this phenomenon is also applicable to other lineages, we have characterized cyanidialean red algae, namely, Cyanidioschyzon merolae, which proliferates by binary fission, as well as Cyanidium caldarium and Galdieria sulphuraria, which form up to four and 32 daughter cells (autospores), respectively, in a mother cell before hatching out. The result shows that there is also a correlation between the number of successive cell divisions and the threshold cell size for cell division or the first round of the successive cell divisions. In both C. merolae and C. caldarium, the cell size checkpoint for cell division(s) exists in the G1-phase, as previously shown in volvocine green algae. When C. merolae cells were arrested in the G1-phase and abnormally enlarged by conditional depletion of CDKA, the cells underwent two or more successive cell divisions without intervening cellular growth after recovery of CDKA, similarly to C. caldarium and G. sulphuraria. These results suggest that the threshold size for cell division is a major factor in determining the number of successive cell divisions and that evolutionary changes in the mechanism of cell size monitoring resulted in a variation of multiple fission cell cycle in eukaryotic algae.

Background Pulmonary hypertension (PH) is characterized by increased pulmonary vascular resistance and right heart failure with progressive narrowing or occlusion of the pulmonary artery. However, the assessment of vascular remodeling is mostly limited to averaged increases in wall thickening, and even the role of vascular endothelial growth factor (VEGF), remains incompletely understood; Although abundantly expressed VEGF is expected to elicit angio-obliteration and the knockout of hypoxia inducible factor (HIF) prevents PH in mice, VEGF inhibitor Sugen exacerbates hypoxia (Hx)-induced PH model, which is referred to as VEGF paradox. Purpose To analyze three-dimensional (3D) spatiotemporal changes of pulmonary microstructure and function, which reflect the disease activity and lead to resolve the paradox. Methods and results We developed a novel 3D visualization system of microstructural networks in whole mouse organ with single-cell resolution, using combined tissue clearing technique called CUBIC and multiphoton excitation microscope. The system enabled the simultaneous 3D evaluation of microvascular structure, invaded macrophages and fibrosis with effective penetration of several mm (whole organ). Three-dimensional observations of PH mice models including Hx, Sugen/Hx, and human-like Alk1+/− hereditary PH models, revealed that not only inward (negative) microvessel remodeling with stenosis, but also marked elongation of microvascular ECs, was evident except Sugen/Hx model at the early phase, which had not been detected by 2D histological sections. Comparable transcriptome analysis revealed that PGC1α, which regulates HIF-independent VEGF expression and angiogenesis, plays an important role in the characteristic response for mitochondrial and microvascular maintenance. PGC1α was up-regulated in the early phage in Hx and Alk1+/− PH models with microvascular angiogenetic change, whereas Sugen/Hx-model did not increase PGC1α expression and did not show microvascular remodeling. Furthermore pulmonary ECs-specific PGC1α-deficient mice exacerbated Hx-PH model with decreased VEGF expression and microvessel density, and administration of Baicalin, a flavonoid enhancing PGC1α expression, ameliorated Hx-PH model with increased VEGF expression. Conclusions The 3D visualization system disclosed an unexpected change of angiogenic microvascular structure in the early phage of PH, which is regulated by EC PGC1α. Microvascular angiogenesis which is induced by up-regulation in PGC1α -VEGF pathway is a crucial factor for compensation of PH in the early phase, which provides a potential novel therapeutic target for PH. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): JSJP

Pulmonary valve stenosis (PVS) accounts for approximately 10% of all congenital heart defects. Echocardiography and right heart catheterization are the gold standards for diagnosis of PVS and for assessing disease severity and responsiveness to treatment.Recently, cardiac magnetic resonance imaging (cMRI) has been established as an important tool to comprehensively evaluate cardiac structure and function; however, research into the usefulness of cMRI for PVS management is limited. Here, we describe a case of a 59-year-old female with isolated, severe PVS who was successfully treated with balloon pulmonary valvuloplasty (BPV) followed by sequential cMRI at 1 and 12 months. Exertional dyspnea and elevated plasma BNP concentration were observed 1 month after BPV; however, echocardiographic findings did not indicate recurrent stenosis or increased pulmonary valve regurgitation but an increase in mitral E/e'. cMRI demonstrated improved systolic forward flow and RV function with enlargement of LV volume, and the rapid increase in LV preload might be associated with the transient deterioration in symptoms and BNP level, which both gradually improved within 3 months after BPV. cMRI further depicted that a reduced RV mass index and increased RV cardiac output were achieved gradually during the follow-up period.In conclusion, cMRI in combination with echocardiography was sufficiently informative to follow-up this PVS patient both before and after BPV. cMRI is easily reproducible in adult patients; therefore, cMRI should be recommended for long-term follow-up in adult PVS patients.

Microalgae possess high potential for producing pigments, antioxidants, and lipophilic compounds for industrial applications. However, their open pond cultures are often contaminated by other undesirable organisms, including their predators. In addition, the cost of using freshwater is relatively high, which limits the location and scale of cultivation compared with using seawater. It was previously shown that Cyanidium caldarium and Galdieria sulphuraria, but not Cyanidioschyzon merolae grew in media containing NaCl at a concentration equivalent to seawater. We found that the preculture of C. merolae in the presence of a moderate NaCl concentration enabled the cells to grow in the seawater-based medium. The cultivation of cyanidialean red algae in the seawater-based medium did not require additional pH buffering chemicals. In addition, the combination of seawater and acidic conditions reduced the risk of contamination by other organisms in the nonsterile open culture of C. merolae more efficiently than the acidic condition alone.

Background: DPP-4 inhibitors have been reported to have beneficial effects on endothelial function as sitagliptin increases circulating endothelial progenitor cells (EPCs) via inhibition of plasma stromal derived factor-1 alpha (SDF-1α). However, its mechanisms are unclear. We evaluated whether DPP-4 inhibitor teneligliptin increases the number of circulating EPCs through inhibition of SDF-1α metabolism and improves flow mediated vascular dilatation (FMD) in type 2 diabetes mellitus (T2DM) patients with acute coronary syndrome (ACS) or its risk factors. Methods: This study was a prospective, single-center, open-label, randomized controlled trial. A total of 16 patients with present or past history of ACS or multiple cardiovascular risk factors were enrolled, and who take any medicine for diabetes, whose HbA1c > 7.5% and/or peak CPK > 2000 IU/ml, were excluded. Variable of glucose and lipids, the number of EPCs, activity levels of DPP-4 and SDF-1α and FMD were evaluated at baseline and at 28±4 weeks after enrollment in all patients. They were randomly assigned into 2 groups either 20mg per day teneligliptin or control. Finally, 8 patients were included in teneligliptin group and 8 in control. All data were analyzed by paired t-test, and p < 0.05 was considered statistically significant. Results: DPP-4 activity (∆-509.5±105.7 vs. ∆32.8±53.4 μU/ml) and SDF-1α levels (∆-695.6±443.2 vs. ∆11.1±193.7 pg/ml) were significantly decreased after 28 weeks in teneligliptin group compared to control, respectively. Number of EPCs, and variables of glucose and lipids were not significantly different between two groups before and after 28 weeks. However, FMD was significantly improved in the teneligliptin group compared to control (∆3.8±2.1 vs. ∆-0.3±2.9%, p = 0.006) after 28 weeks treatment. Conclusion: These results indicate that teneligliptin improves FMD by different mechanisms from the increase of blood EPC number via SDF-1α. Disclosure N. Akashi: None. T. Umemoto: None. Y. Hodaka: None. T. Fujiwara: None. K. Yamamoto: None. Y. Taniguchi: None. K. Sakakura: None. H. Wada: None. S. Momomura: None. H. Fujita: None.

[Purpose] The purpose of this study was to compare the range of motion (ROM) during supine-to-sitting position (StSP) movement between healthy young and elderly participants to understand age-related tendencies, which is beneficial for the assessment and treatment of frail elderly. [Participants and Methods] The participants were 14 healthy young males (age, 19-24 years) and 16 healthy elderly individuals (8 males and 8 females; age, 65-74 years). Rising movement was performed 5 times freely at a comfortable speed. [Results] The joint angles during StSP movements in right shoulder abduction, extension of both shoulder joints, right elbow flexion, trunk extension, and adduction of both hip joints were significantly larger, whereas neck flexion, trunk flexion, and left hip joint abduction were significantly smaller in the healthy elderly participants than in the healthy young participants. All joint movements were earlier in the elderly participants than in the healthy young participants. [Conclusion] The results of this study suggest that focusing on how to use both upper limbs is important, in addition to the neck and trunk, when evaluating StSP movement. Similarly, to encourage independence during StSP movement, the elbow extensors must be strengthened.

Metabolism, cell cycle stages, and related transcriptomes in eukaryotic algae change with the diel cycle of light availability. In the unicellular red alga Cyanidioschyzon merolae, the S and M phases occur at night. To examine how diel transcriptomic changes in metabolic pathways are related to the cell cycle and to identify all genes for which mRNA levels change depending on the cell cycle, we examined diel transcriptomic changes in C. merolae In addition, we compared transcriptomic changes between the wild type and transgenic lines, in which the cell cycle was uncoupled from the diel cycle by the depletion of either cyclin-dependent kinase A or retinoblastoma-related protein. Of 4,775 nucleus-encoded genes, the mRNA levels of 1,979 genes exhibited diel transcriptomic changes in the wild type. Of these, the periodic expression patterns of 454 genes were abolished in the transgenic lines, suggesting that the expression of these genes is dependent on cell cycle progression. The periodic expression patterns of most metabolic genes, except those involved in starch degradation and de novo deoxyribonucleotide triphosphate synthesis, were not affected in the transgenic lines, indicating that the cell cycle and transcriptomic changes in most metabolic pathways are independent of the diel cycle. Approximately 40% of the cell-cycle-dependent genes were of unknown function, and approximately 19% of these genes of unknown function are shared with the green alga Chlamydomonas reinhardtii The data set presented in this study will facilitate further studies on the cell cycle and its relationship with metabolism in eukaryotic algae.

This study investigated the effectiveness and safety of interval training during in-hospital treatment of patients with advanced heart failure. Twenty-four consecutive patients with advanced symptomatic heart failure who were referred for cardiac transplant evaluation were recruited. After performing aerobic exercise for approximate intensity, high-intensity interval training (HIIT) was performed. The protocol consisted of 3 or 4 sessions of 1-min high-intensity exercise aimed at 80% of peak VO

This article demonstrates a kinetic approach to partially overlapping multistep chemical reactions in solid-gas systems as exemplified by the thermal decomposition of granular sodium perborate tetrahydrate. This reaction proceeds via successive thermal dehydration and decomposition occurring at different temperatures to form sodium metaborate. Each reaction process comprises several kinetic steps originating from different physicochemical and physico-geometric phenomena. The partially overlapping multistep processes were characterized using available thermoanalytical techniques and microscopic observations. Conventional isoconversional kinetic analysis and empirical mathematical deconvolution were applied to each reaction process as preliminary kinetic approaches to extracting provable kinetic information. Then, each reaction process was analyzed kinetically based on a cumulative kinetic equation, i.e., kinetic deconvolution analysis. The results of the kinetic deconvolution analysis were further examined by comparison with other kinetic information for the specific kinetic steps obtained from different thermoanalytical measurements. From the results of this comprehensive kinetic approach, the kinetic features of the thermal dehydration and decomposition processes were revealed by identifying their contributing physicochemical and physico-geometric phenomena and evaluating their influences on the overall multistep processes.

Supramolecular adhesives (SAs) have attracted great interest as a promising adhesion methodology in many fields. Although various SAs employing well-established non-covalent motifs have been reported to date, examples with marked binding strengths >2 MPa are still limited to SAs based on specific high-energy non-covalent interactions, e.g. hydrogen bonds, ionic bonds, host–guest interactions, and metal–ligand complexations. Reported herein is a new class of SAs based on multiple CH/π interactions. We designed the SAs with multiple-naphthalene-ring-functionalised polyacrylamide as a π donor and a polyolefin consisting of alkyl groups as a π acceptor. The macroscopic supramolecular assemblies achieved binding strengths in the range 2.1–2.6 MPa, comparable to those of SAs based on high-energy non-covalent interactions. Moreover, the adhesive exhibited long-term (i.e. 30 days) stability in wet and humid environments. Finally, we demonstrated potential application of our adhesive as an industrial adhesive. Our SAs will overturn the preconception that adhesion strength driven by low-energy non-covalent interactions is low, and they hold potential for a range of useful applications in chemistry, materials science, and relevant industrial manufacturing.

Mitochondria, which evolved from a free-living bacterial ancestor, contain their own genomes and genetic systems and are produced from preexisting mitochondria by binary division. The mitochondrion-dividing (MD) ring is the main skeletal structure of the mitochondrial division machinery. However, the assembly mechanism and molecular identity of the MD ring are unknown. Multi-omics analysis of isolated mitochondrial division machinery from the unicellular alga Cyanidioschyzon merolae revealed an uncharacterized glycosyltransferase, MITOCHONDRION-DIVIDING RING1 (MDR1), which is specifically expressed during mitochondrial division and forms a single ring at the mitochondrial division site. Nanoscale imaging using immunoelectron microscopy and componential analysis demonstrated that MDR1 is involved in MD ring formation and that the MD ring filaments are composed of glycosylated MDR1 and polymeric glucose nanofilaments. Down-regulation of MDR1 strongly interrupted mitochondrial division and obstructed MD ring assembly. Taken together, our results suggest that MDR1 mediates the synthesis of polyglucan nanofilaments that assemble to form the MD ring. Given that a homolog of MDR1 performs similar functions in chloroplast division, the establishment of MDR1 family proteins appears to have been a singular, crucial event for the emergence of endosymbiotic organelles.

In many eukaryotes, cytokinesis proceeds in two successive steps: first, ingression of the cleavage furrow and second, abscission of the intercellular bridge. In animal cells, the actomyosin contractile ring is involved in the first step, while the endosomal sorting complex required for transport (ESCRT), which participates in various membrane fusion/fission events, mediates the second step. Intriguingly, in archaea, ESCRT is involved in cytokinesis, raising the hypothesis that the function of ESCRT in eukaryotic cytokinesis descended from the archaeal ancestor. In eukaryotes other than in animals, the roles of ESCRT in cytokinesis are poorly understood. To explore the primordial core mechanisms for eukaryotic cytokinesis, we investigated ESCRT functions in the unicellular red alga Cyanidioschyzon merolae that diverged early in eukaryotic evolution. C. merolae provides an excellent experimental system. The cell has a simple organelle composition. The genome (16.5 Mb, 5335 genes) has been completely sequenced, transformation methods are established, and the cell cycle is synchronized by a light and dark cycle. Similar to animal and fungal cells, C. merolae cells divide by furrowing at the division site followed by abscission of the intercellular bridge. However, they lack an actomyosin contractile ring. The proteins that comprise ESCRT-I–IV, the four subcomplexes of ESCRT, are partially conserved in C. merolae. Immunofluorescence of native or tagged proteins localized the homologs of the five ESCRT-III components [charged multivesicular body protein (CHMP) 1, 2, and 4–6], apoptosis-linked gene-2-interacting protein X (ALIX), the ESCRT-III adapter, and the main ESCRT-IV player vacuolar protein sorting (VPS) 4, to the intercellular bridge. In addition, ALIX was enriched around the cleavage furrow early in cytokinesis. When the ESCRT function was perturbed by expressing dominant-negative VPS4, cells with an elongated intercellular bridge accumulated—a phenotype resulting from abscission failure. Our results show that ESCRT mediates cytokinetic abscission in C. merolae. The fact that ESCRT plays a role in cytokinesis in archaea, animals, and early diverged alga C. merolae supports the hypothesis that the function of ESCRT in cytokinesis descended from archaea to a common ancestor of eukaryotes.

It is expected that the criteria would propose the inspection system for detecting the power line of unusual condition such as the damage or the aged deterioration. In this paper, we propose the method for classification of powerline surface using CNN. We have been developing the inspection mobile robot that is automated moving device with mounted camera. As things stand at the moment, we try to realize the support for visual inspection by operator from remote location before the machine inspection. Therefore, we propose a system for the operator to visual inspections efficiently. We are supposed to propose the classification method for the defect of power line surface. In this paper, we propose the method of the detection for the snow resistant ring experimentally.

BACKGROUND The effect of the sex ratio of the team of the attending doctors on clinical outcomes remains unknown.Methods and Results:This retrospective cohort study included 9,544 patients admitted between 2012 and 2018 for cardiovascular diseases. They were treated by teams of 3 attending doctors comprising a trainee doctor, middle-grade cardiologist who played the main role in the clinical management, and upper-grade cardiologist who was responsible for the management. We explored whether the sex of the attending doctors influenced the risk of emergency readmission within 30 days after discharge. The primary hospitalization periods were similar for male and female middle-grade cardiologists. The risk of emergency readmission of patients hospitalized with cardiovascular diseases was significantly higher for patients treated by male middle-grade cardiologists than in those treated by female middle-grade cardiologists (odds ratio: 2.09, P