853 research outputs found

    Kummer-type congruences for multi-poly-Bernoulli numbers

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    The multi-poly-Bernoulli numbers are generalizations of the Bernoulli numbers. In this paper, we will prove Kummer-type congruences for multi-poly-Bernoulli numbers via pp-adic distributions.Comment: 11 page

    非アルキメデス的関数解析とその応用

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    Tohoku University山崎隆雄課

    Human iPSC-derived renal collecting duct organoid model cystogenesis in ADPKD

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    腎集合管オルガノイドを用いた多発性嚢胞腎モデルの作製 iPS創薬により治療薬候補を発見、治験開始へ. 京都大学プレスリリース. 2023-12-01.Developing more advanced renal organoids to model polycystic kidney disease. 京都大学プレスリリース. 2023-12-01.In autosomal dominant polycystic kidney disease (ADPKD), renal cyst lesions predominantly arise from collecting ducts (CDs). However, relevant CD cyst models using human cells are lacking. Although previous reports have generated in vitro renal tubule cyst models from human induced pluripotent stem cells (hiPSCs), therapeutic drug candidates for ADPKD have not been identified. Here, by establishing expansion cultures of hiPSC-derived ureteric bud tip cells, an embryonic precursor that gives rise to CDs, we succeed in advancing the developmental stage of CD organoids and show that all CD organoids derived from PKD1−/− hiPSCs spontaneously develop multiple cysts, clarifying the initiation mechanisms of cystogenesis. Moreover, we identify retinoic acid receptor (RAR) agonists as candidate drugs that suppress in vitro cystogenesis and confirm the therapeutic effects on an ADPKD mouse model in vivo. Therefore, our in vitro CD cyst model contributes to understanding disease mechanisms and drug discovery for ADPKD

    Trans-omics Impact of Thymoproteasome in Cortical Thymic Epithelial Cells

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    The thymic function to produce self-protective and self-tolerant T cells is chiefly mediated by cortical thymic epithelial cells (cTECs) and medullary TECs (mTECs). Recent studies including single-cell transcriptomic analyses have highlighted a rich diversity in functional mTEC subpopulations. Because of their limited cellularity, however, the biochemical characterization of TECs, including the proteomic profiling of cTECs and mTECs, has remained unestablished. Utilizing genetically modified mice that carry enlarged but functional thymuses, here we show a combination of proteomic and transcriptomic profiles for cTECs and mTECs, which identified signature molecules that characterize a developmental and functional contrast between cTECs and mTECs. Our results reveal a highly specific impact of the thymoproteasome on proteasome subunit composition in cTECs and provide an integrated trans-omics platform for further exploration of thymus biology

    Individual hematopoietic stem cells in human bone marrow of patients with aplastic anemia or myelodysplastic syndrome stably give rise to limited cell lineages

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    Mutation of the phosphatidylinositol N-acetylglucosaminyltransferase subunit A (PIG-A) gene in hematopoietic stem cells (HSCs) results in the loss of glycosylphosphatidylinositol- anchored proteins (GPI-APs) on HSCs, but minimally affects their development, and thus can be used as a clonal maker of HSCs. We analyzed GPI-APs expression on six major lineage cells in a total of 574 patients with bone marrow (BM) failure in which microenvironment itself is thought to be unaffected, including aplastic anemia (AA) or myelodysplastic syndrome (MDS). GPI-APs-deficient (GPIAPs-) cells were detected in 250 patients. Whereas the GPIAPs- cells were seen in all six lineages in a majority of patients who had higher proportion ([dbmtequ]3%) of GPIAPs- cells, they were detected in only limited lineages in 92.9% of cases in the lower proportion (<3%) group. In all 250 cases, the same lineages of GPI-APs- cells were detected even after 6-18-month intervals, indicating that the GPIAPs- cells reflect hematopoiesis maintained by a self-renewing HSC in most of cases. The frequency of clones with limited lineages seen in mild cases of AA was similar to that in severe cases, and clones with limited lineages were seen even in two health volunteer cases. These results strongly suggest most individual HSCs produce only restricted lineages even in a steady state. While this restriction could reflect heterogeneity in the developmental potential of HSCs, we propose an alternative model in which the BM microenvironment is mosaic in supporting commitment of progenitors toward distinct lineages. Our computer simulation based on this model successfully recapitulated the observed clinical data. © AlphaMed Press

    Electrochemical integration of graphene with light absorbing copper-based thin films

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    We present an electrochemical route for the integration of graphene with light sensitive copper-based alloys used in optoelectronic applications. Graphene grown using chemical vapor deposition (CVD) transferred to glass is found to be a robust substrate on which photoconductive Cu_{x}S films of 1-2 um thickness can be deposited. The effect of growth parameters on the morphology and photoconductivity of Cu_{x}S films is presented. Current-voltage characterization and photoconductivity decay experiments are performed with graphene as one contact and silver epoxy as the other
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