Atomic-scale flattening of SiC surfaces by electroless chemical etching in HF solution with Pt catalyst

The authors present a method for flattening SiC surfaces with Pt as a catalyst in HF solution. The mechanism for flattening SiC surfaces is discussed. The flattened 4H-SiC (0001) surface is composed of alternating wide and narrow terraces with single-bilayer-height steps, which are induced by the rate difference of the catalytic reactions between adjacent terraces. Scanning tunneling microscopy images reveal a 1×1 phase on the terraces. The 1×1 phase is composed of coexisting of F- and OH-terminated Si atoms, which originate from the polarization of the underlying Si-C bonds. © 2007 American Institute of Physics.Kenta Arima, Hideyuki Hara, et al. "Atomic-scale flattening of SiC surfaces by electroless chemical etching in HF solution with Pt catalyst", Appl. Phys. Lett. 90(20), 202106 (2007) https://doi.org/10.1063/1.2739084

X-ray magnetic circular dichroism and photoemission study of the diluted ferromagnetic semiconductor Zn1−x_{1-x}Crx_xTe

We have performed x-ray magnetic circular dichroism (XMCD) and valence-band photoemission studies of the diluted ferromagnetic semiconductor Zn$_{1-x}$Cr$_x$Te. XMCD signals due to ferromagnetism were observed at the Cr 2p absorption edge. Comparison with atomic multiplet calculations suggests that the magnetically active component of the Cr ion was divalent under the tetrahedral crystal field with tetragonal distortion along the crystalline a-, b-, and c-axes. In the valence-band spectra, spectral weight near the Fermi level was strongly suppressed, suggesting the importance of Jahn-Teller effect and the strong Coulomb interaction between the Cr 3d electrons

Isogenic pairs of induced-pluripotent stem-derived endothelial cells identify DYRK1A/PPARG/EGR1 pathway is responsible for Down syndrome-associated pulmonary hypertension

Down syndrome (DS) is the most prevalent chromosomal disorder associated with a higher incidence of pulmonary arterial hypertension (PAH). The dysfunction of vascular endothelial cells (ECs) is known to cause pulmonary arterial remodeling in PAH, although the physiological characteristics of ECs harboring trisomy 21 (T21) are still unknown. In this study, we analyzed the human vascular ECs by utilizing the isogenic pairs of T21-induced pluripotent stem cells (iPSCs) and corrected disomy 21 (cDi21)-iPSCs. In T21-iPSC-derived ECs, apoptosis and mitochondrial reactive oxygen species (mROS) were significantly increased, and angiogenesis and oxygen consumption rate (OCR) were significantly impaired as compared with cDi21-iPSC-derived ECs. The RNA-sequencing identified that EGR1 on chromosome 5 was significantly upregulated in T21-ECs. Both EGR1 suppression by siRNA and pharmacological inhibitor could recover the apoptosis, mROS, angiogenesis, and OCR in T21-ECs. Alternately, the study also revealed that DYRK1A was responsible to increase EGR1 expression via PPARG suppression, and that chemical inhibition of DYRK1A could restore the apoptosis, mROS, angiogenesis, and OCR in T21-ECs. Finally, we demonstrated that EGR1 was significantly upregulated in the pulmonary arterial ECs from lung specimens of a patient with DS and PAH. In conclusion, DYRK1A/PPARG/EGR1 pathway could play a central role for the pulmonary EC functions and thus be associated with the pathogenesis of PAH in DS.Suginobe Hidehiro, Ishida Hidekazu, Ishii Yoichiro, et al. Isogenic pairs of induced-pluripotent stem-derived endothelial cells identify DYRK1A/PPARG/EGR1 pathway is responsible for Down syndrome-associated pulmonary hypertension. Human Molecular Genetics 163, 1163 (2023); https://doi.org/10.1093/hmg/ddad162

Clinical Outcomes and Genetic Analyses of Restrictive Cardiomyopathy in Children

BACKGROUND: Restrictive cardiomyopathy in children is rare and outcomes are very poor. However, little information is available concerning genotype-outcome correlations. METHODS: We analyzed the clinical characteristics and genetic testing, including whole exome sequencing, of 28 pediatric restrictive cardiomyopathy patients who were diagnosed from 1998 to 2021 at Osaka University Hospital in Japan. RESULTS: The median age at diagnosis (interquartile range) was 6 (2.25-8.5) years. Eighteen patients received heart transplantations and 5 patients were on the waiting list. One patient died while waiting for transplantation. Pathologic or likely-pathogenic variants were identified in 14 of the 28 (50%) patients, including heterozygous TNNI3 missense variants in 8 patients. TNNT2, MYL2, and FLNC missense variants were also identified. No significant differences in clinical manifestations and hemodynamic parameters between positive and negative pathogenic variants were detected. However, 2- and 5-year survival rates were significantly lower in patients with pathogenic variants (50% and 22%) compared with survival in patients without pathogenic variants (62% and 54%; P=0.0496, log-rank test). No significant differences were detected in the ratio of patients diagnosed at nationwide school heart disease screening program between positive and negative pathogenic variants. Patients diagnosed by school screening showed better transplant-free survival compared with patients diagnosed by heart failure symptoms (P=0.0027 in log-rank test). CONCLUSIONS: In this study, 50% of pediatric restrictive cardiomyopathy patients had pathogenic or likely-pathogenic gene variants, and TNNI3 missense variants were the most frequent. Patients with pathogenic variants showed significantly lower transplant-free survival compared with patients without pathogenic variants.Ishida H., Narita J., Ishii R., et al. Clinical Outcomes and Genetic Analyses of Restrictive Cardiomyopathy in Children. Circulation: Genomic and Precision Medicine 16, 382 (2023); https://doi.org/10.1161/CIRCGEN.122.004054

Pathogenic Roles of Cardiac Fibroblasts in Pediatric Dilated Cardiomyopathy

BACKGROUND: Dilated cardiomyopathy (DCM) is a major cause of heart failure in children. Despite intensive genetic analyses, pathogenic gene variants have not been identified in most patients with DCM, which suggests that cardiomyocytes are not solely responsible for DCM. Cardiac fibroblasts (CFs) are the most abundant cell type in the heart. They have several roles in maintaining cardiac function; however, the pathological role of CFs in DCM remains unknown. METHODS AND RESULTS: Four primary cultured CF cell lines were established from pediatric patients with DCM and compared with 3 CF lines from healthy controls. There were no significant differences in cellular proliferation, adhesion, migration, ap-optosis, or myofibroblast activation between DCM CFs compared with healthy CFs. Atomic force microscopy revealed that cellular stiffness, fluidity, and viscosity were not significantly changed in DCM CFs. However, when DCM CFs were cocultured with healthy cardiomyocytes, they deteriorated the contractile and diastolic functions of cardiomyocytes. RNA sequencing revealed markedly different comprehensive gene expression profiles in DCM CFs compared with healthy CFs. Several hu-moral factors and the extracellular matrix were significantly upregulated or downregulated in DCM CFs. The pathway analysis revealed that extracellular matrix receptor interactions, focal adhesion signaling, Hippo signaling, and transforming growth factor-β signaling pathways were significantly affected in DCM CFs. In contrast, single-cell RNA sequencing revealed that there was no specific subpopulation in the DCM CFs that contributed to the alterations in gene expression. CONCLUSIONS: Although cellular physiological behavior was not altered in DCM CFs, they deteriorated the contractile and diastolic functions of healthy cardiomyocytes through humoral factors and direct cell–cell contact.Tsuru H., Yoshihara C., Suginobe H., et al. Pathogenic Roles of Cardiac Fibroblasts in Pediatric Dilated Cardiomyopathy. Journal of the American Heart Association 12, e029676 (2023); https://doi.org/10.1161/JAHA.123.029676

DIDS, a chemical compound that inhibits RAD51-mediated homologous pairing and strand exchange

RAD51, an essential eukaryotic DNA recombinase, promotes homologous pairing and strand exchange during homologous recombination and the recombinational repair of double strand breaks. Mutations that up- or down-regulate RAD51 gene expression have been identified in several tumors, suggesting that inappropriate expression of the RAD51 activity may cause tumorigenesis. To identify chemical compounds that affect the RAD51 activity, in the present study, we performed the RAD51-mediated strand exchange assay in the presence of 185 chemical compounds. We found that 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS) efficiently inhibited the RAD51-mediated strand exchange. DIDS also inhibited the RAD51-mediated homologous pairing in the absence of RPA. A surface plasmon resonance analysis revealed that DIDS directly binds to RAD51. A gel mobility shift assay showed that DIDS significantly inhibited the DNA-binding activity of RAD51. Therefore, DIDS may bind near the DNA binding site(s) of RAD51 and compete with DNA for RAD51 binding

ナンセイショトウ ノ ジセイショクブツシゲン ノ ユウヨウセイ ト トクサンカ ノ カノウセイ : イエジマ ニ オケル マーナ ワメイ : ハマカブラ ノ セイブントクセイ ト ヒョウカ

本研究は,南西諸島のような物理的・環境的条件の限定された地域における在来的な自生植物資源の有用性に関する研究である。沖縄県伊江村(伊江島)では,アブラナ科のハマカブラBrassica campestris L.を,マーナと称し,島の人々はかねてから利用してきた。この植物は日本全国で確認されているが,沖縄県においては自生地が限られ,またこれを日常的に食しているのは伊江島だけといわれている。雑草であるがゆえに,この植物の生産に取り組んでいる農家は,2戸に過ぎない。われわれはこのマーナに関する一般的特性に関する聞き取り調査をおこない,さらに栄養分析をおこなった。その結果,特にマーナのポリフェノール含有量は比較的高い数値で,一般的な野菜の10倍程度であった。日常的に利用されながら雑草的な扱いにとどまっているが,成分的には機能性に加え,栄養学的な面でも優れていることが示され,今後食用化が進められるべき素材であることが示唆された。伊江島では製糖工場が閉鎖され,農家の高齢化も伴って耕作放棄が目立ちつつある中で,ラッカセイ,トウガン,花卉につぐ,マーナの特産化が模索されるべきであろう。The purpose of this study is to suggest utilizing volunteer plant resources in the region such as the southwest islands, where growth is limited by physical and environmental conditions. Brassica campestris L. also known in dialect as "maana", is a kind of weed found all over Japan. In particular, people of Ie-island in the Okinawa Prefecture use them frequently. It is treated as a "weed", but there are two farmers who produce it on economic base. We researched the general growing conditions and nutritional value of Brassica campestris L.. To determine the effective use of Brassica campestris L., we studied its chemical components and nutritive values. In particular, Brassica campestris L. contains a large amount of dietary fiber. Mineral content, particularly iron, and vitamin content such as beta carotene and vitamin C were high in comparison with other vegetables. Furthermore, polyphenol content was comparatively high. Thus, its chemical component was similar to that of a green vegetable. We suggest changing Brassica campestris L.\u27s status as a "mere weed" and further capitalizing on the utilization of these volunteer plant resources. To promote maana as a special product, we should first recognize the utilization of volunteer plant resources at first, secondly analyze the habits of such volunteer plant, and develop the agricultural technology for a farming system

Single-Cell Expression Profiling Reveals a Dynamic State of Cardiac Precursor Cells in the Early Mouse Embryo

In the early vertebrate embryo, cardiac progenitor/precursor cells (CPs) give rise to cardiac structures. Better understanding their biological character is critical to understand the heart development and to apply CPs for the clinical arena. However, our knowledge remains incomplete. With the use of single-cell expression profiling, we have now revealed rapid and dynamic changes in gene expression profiles of the embryonic CPs during the early phase after their segregation from the cardiac mesoderm. Progressively, the nascent mesodermal gene Mesp1 terminated, and Nkx2-5+/Tbx5+ population rapidly replaced the Tbx5low+ population as the expression of the cardiac genes Tbx5 and Nkx2-5 increased. At the Early Headfold stage, Tbx5-expressing CPs gradually showed a unique molecular signature with signs of cardiomyocyte differentiation. Lineage-tracing revealed a developmentally distinct characteristic of this population. They underwent progressive differentiation only towards the cardiomyocyte lineage corresponding to the first heart field rather than being maintained as a progenitor pool. More importantly, Tbx5 likely plays an important role in a transcriptional network to regulate the distinct character of the FHF via a positive feedback loop to activate the robust expression of Tbx5 in CPs. These data expands our knowledge on the behavior of CPs during the early phase of cardiac development, subsequently providing a platform for further study