108 research outputs found

    Committed neuronal precursors confer astrocytic potential on residual neural precursor cells

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    During midgestation, mammalian neural precursor cells (NPCs) differentiate only into neurons. Generation of astrocytes is prevented at this stage, because astrocyte-specific gene promoters are methylated. How the subsequent switch from suppression to expression of astrocytic genes occurs is unknown. We show in this study that Notch ligands are expressed on committed neuronal precursors and young neurons in mid-gestational telencephalon, and that neighboring Notch-activated NPCs acquire the potential to become astrocytes. Activation of the Notch signaling pathway in midgestational NPCs induces expression of the transcription factor nuclear factor I, which binds to astrocytic gene promoters, resulting in demethylation of astrocyte-specific genes. These findings provide a mechanistic explanation for why neurons come first: committed neuronal precursors and young neurons potentiate remaining NPCs to differentiate into the next cell lineage, astrocytes

    Nuclear factor I/A coordinates the timing of oligodendrocyte differentiation/maturation via Olig1 promoter methylation

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    Transcription factors (TFs) and epigenetic modifications function cooperatively to regulate various biological processes such as cell proliferation, differentiation, maturation, and metabolism. TF binding to regulatory regions of target genes controls their transcriptional activity through alteration of the epigenetic status around the binding regions, leading to transcription network formation regulating cell fates. Although nuclear factor I/A (Nfia) is a well-known TF that induces demethylation of astrocytic genes to confer astrocytic differentiation potential on neural stem/precursor cells (NS/PCs), the epigenetic role of NFIA in oligodendrocytic lineage progression remains unclear. Here, we show that oligodendrocyte differentiation/maturation is delayed in the brains of Nfia-knockout (KO) mice, and that NFIA-regulated DNA demethylation in NS/PCs plays an important role in determining the timing of their differentiation. We further demonstrate that the promoter activity of the oligodendrocyte transcription factor 1 (Olig1) gene, involved in oligodendrocyte differentiation/maturation, is suppressed by DNA methylation, which is in turn regulated by Nfia expression. Our results suggest that NFIA controls the timing of oligodendrocytic differentiation/maturation via demethylation of cell-type-specific gene promoters

    Development of a Vertex Finding Algorithm using Recurrent Neural Network

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    Deep learning is a rapidly-evolving technology with possibility to significantly improve physics reach of collider experiments. In this study we developed a novel algorithm of vertex finding for future lepton colliders such as the International Linear Collider. We deploy two networks; one is simple fully-connected layers to look for vertex seeds from track pairs, and the other is a customized Recurrent Neural Network with an attention mechanism and an encoder-decoder structure to associate tracks to the vertex seeds. The performance of the vertex finder is compared with the standard ILC reconstruction algorithm.Comment: 8 pages, 8 figures, preliminary version currently under review by IL

    Factors related to renal cortical atrophy development after glucocorticoid therapy in IgG4-related kidney disease: a retrospective multicenter study.

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    Background: In immunoglobulin G4-related kidney disease (IgG4-RKD), focal or diffuse renal cortical atrophy is often observed in the clinical course after glucocorticoid therapy. This study aimed to clarify the factors related to renal atrophy after glucocorticoid therapy in IgG4-RKD. Methods: We retrospectively evaluated clinical features including laboratory data and computed tomography (CT) findings before and after glucocorticoid therapy in 23 patients diagnosed with IgG4-RKD, all of whom were followed up for more than 24 months. Results: Seventeen patients were men, and six were women (average age 62.0 years). Average follow-up period was 54.9 months. The average estimated glomerular filtration rate (eGFR) at diagnosis was 81.7 mL/min/1.73 m2. All patients had had multiple low-density lesions on contrast-enhanced CT before glucocorticoid therapy, and showed disappearance or reduction of these lesions after it. Pre-treatment eGFR and serum IgE level in 11 patients in whom renal cortical atrophy developed 24 months after the start of glucocorticoid therapy were significantly different from those in 12 patients in whom no obvious atrophy was found at that time (68.9 ± 30.1 vs 93.5 ± 14.1 mL/min/1.73 m2, P = 0.036, and 587 ± 254 vs 284 ± 263 IU/mL, P = 0.008, respectively). Pre-treatment eGFR and serum IgE level were also significant risk factors for renal atrophy development 24 months after the start of therapy with an odds ratio of 0.520 (per 10 mL/min/1.73 m2, 95% confidence interval (CI) 0.273-0.993, P = 0.048) and 1.090 (per 10 IU/mL, 95% CI: 1.013-1.174, P = 0.022), respectively, in age-adjusted, sex-adjusted, serum IgG4 level-adjusted logistic regression analysis. Receiver operating characteristic curve analysis showed that eGFR of less than 71.0 mL/min/1.73 m2 and serum IgE of more than 436.5 IU/mL were the most appropriate cutoffs and yielded sensitivity of 63.6% and specificity of 100%, and sensitivity of 90.9% and specificity of 75.0%, respectively, in predicting renal atrophy development. Conclusions: This study suggests that pre-treatment renal insufficiency and serum IgE elevation predict renal atrophy development after glucocorticoid therapy in IgG4-RKD. © 2016 The Author(s)

    Skin Tube Reconstruction for Esophageal Defects due to Postoperative Complications: Applying a skin flap in esophageal resection and reconstruction

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    Numerous improvements and advances in operational methods and techniques have occurred in the area of reconstruction for esophageal cancer. Patients with thoracic esophageal cancer who have previously had a gastrectomy usually undergo reconstruction using the colon and small intestine. The incidence of organ necrosis is not necessarily low after reconstruction with those organs. Generally, the main types of skin flaps and musculocutaneous flaps used for cervical and other esophageal reconstructions are deltopectoral (DP) flaps, pedicled musculocutaneous latissimus dorsi flaps and free anteriolateral thigh flaps. This kind of reconstruction is low invasive, relatively simple, and also causes very few fatal post-operative complications. Therefore, it is considered to be an effective reconstruction choice for the following types of patients: poor risk patients, patients whose gastrointestinal (GI) tract cannot be used for their reconstruction for some reason, and patients having a second reconstruction due to complications caused by organ necrosis after their first GI tract reconstruction

    A Case of Cholesterol Crystal Embolization with Hemorrhagic Intestinal Ulcer

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    Cholesterol crystal embolization (CCE) is a rare systemic embolism caused by formation of cholesterol crystals from atherosclerotic plaques. CCE usually occurs during vascular manipulation such as vascular surgery or endovascular catheter manipulation, or due to anticoagulation or thrombolytic therapy. We report a rare case of localized intestinal ulcer with active hemorrhage caused by spontaneous CCE. An 83-year-old man with a history of hypertension and diabetes was treated with a percutaneous coronary intervention (PCI) for myocardial infarction. Melena occurred eight days after PCI. An abdominal computed tomography revealed small intestinal ulcer, extravasation of the gastrointestinal tract and bleeding in the abdominal cavity. The patient was diagnosed as bleeding from the small intestinal ulcer, so an emergency laparotomy was performed. Partial resection of the small intestine was performed. A histopathological examination indicated that small intestine obstruction was caused by CCE. A histopathological examination indicated that small intestinal obstruction was caused by CCE. Therefore, in cases of intestinal obstruction after vascular manipulation, CCE should also be considered

    Evaluation of intra-ductal cancer spread using contrast superb micro-vascular imaging (SMI) : a case report

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    Currently, breast conserving surgery has been adopted to treat more than half of all breast cancer patients in Japan. When performing breast-conserving surgery, an appropriate margin needs to be determined for radical cure. The resection volume influences the esthetic outcome, but a cancer-positive resection stump is also important risk factor of local recurrence. Additionally, the degree of cancer progression influences the surgical method, so understanding the appropriate resection margin is necessary for the surgeons. We report here on a 50- year old patient whose intra-ductal cancer progression was shown, as predicted, by contrast SMI (superb micro-vascular imaging). A one-cm size tumor mass was palpable with a clear boundary. B-mode ultrasound confirmed the presence of a breast duct towards the nipple from the tumor mass. Using contrast SMI, an accelerated blood flow was detected around the duct, which suggested intra-ductal progression. The pathological results also showed intra-ductal progression to the nipple from the tumor. Around the progression area, a meandering vessel was found and the vessel was able to be visualized by contrast SMI
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