Publications by authors named "Takubo K"

Telomeres in most somatic cells shorten with each cell division, and critically short telomeres lead to cellular dysfunction, cell cycle arrest, and senescence. Thus, telomere shortening is an important hallmark of human cellular senescence. Quantitative fluorescence in situ hybridization (Q-FISH) using formalin-fixed paraffin-embedded (FFPE) tissue sections allows the estimation of telomere lengths in individual cells in histological sections.

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There are currently no standard methods for diagnosing cardiac diseases in dolphins. These diseases may consequently be overlooked and go undiagnosed. The presence and severity of cardiac diseases in humans can be determined using blood tests.

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Article Synopsis
  • Aging affects stem cells, leading to decreased function and impacting tissue health, but hematopoietic stem cells (HSCs) develop a resilience that helps them survive.* -
  • Old HSCs shift their metabolism by activating the pentose phosphate pathway, allowing them to resist oxidative stress and operate independently of glycolysis.* -
  • The study reveals that old HSCs enhance energy production through mitochondrial changes, aided by increased levels of a specific factor (SDHAF1), improving their survival during stress and addressing age-related blood cell formation issues.*
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Inhibitory natural killer (NK) cell receptors recognize MHC class I (MHC-I) in on target cells and suppress cytotoxicity. Some NK cell receptors recognize MHC-I in , but the role of this interaction is uncertain. Ly49Q, an atypical Ly49 receptor expressed in non-NK cells, binds MHC-I in and mediates chemotaxis of neutrophils and type I interferon production by plasmacytoid dendritic cells.

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Metabolic pathways are plastic and rapidly change in response to stress or perturbation. Current metabolic profiling techniques require lysis of many cells, complicating the tracking of metabolic changes over time after stress in rare cells such as hematopoietic stem cells (HSCs). Here, we aimed to identify the key metabolic enzymes that define differences in glycolytic metabolism between steady-state and stress conditions in murine HSCs and elucidate their regulatory mechanisms.

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Erythropoiesis in the adult bone marrow relies on mitochondrial membrane transporters to facilitate heme and hemoglobin production. Erythrocytes in the bone marrow are produced although the differentiation of erythroid progenitor cells that originate from hematopoietic stem cells (HSCs). Whether and how mitochondria transporters potentiate HSCs and affect their differentiation toward erythroid lineage remains unclear.

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Clinicopathological and molecular studies have demonstrated that dysplasia is a precancerous and/or neoplastic lesion with malignant potential. Further, it is subclassified into two grades: high-grade and low-grade dysplasia. High-grade dysplasia is a clinically significant lesion requiring resection or ablation.

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Imeglimin is a recently developed anti-diabetic drug that could concurrently promote insulin secretion and insulin sensitivity, while its mechanisms of action are not fully understood. Here we show that imeglimin administration could protect mice from high fat diet-induced weight gain with enhanced energy expenditure and attenuated whitening of brown adipose tissue. Imeglimin administration led to significant alteration of gut microbiota, which included an increase of Akkermansia genus, with attenuation of obesity-associated gut pathologies.

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Bone marrow endothelial cells (BMECs) play a key role in bone formation and haematopoiesis. Although recent studies uncovered the cellular taxonomy of stromal compartments in the bone marrow (BM), the complexity of BMECs is not fully characterized. In the present study, using single-cell RNA sequencing, we defined a spatial heterogeneity of BMECs and identified a capillary subtype, termed type S (secondary ossification) endothelial cells (ECs), exclusively existing in the epiphysis.

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Hematopoietic stem and progenitor cells in mammals primarily reside in the bone marrow after birth. There, the cellular dynamics and subsequent fate of those cells are regulated by the adjacent microenvironment, known as the niche, to sustain lifelong blood cell production. To analyze and study physiological hematopoiesis and various hematopoietic disorders, it is essential to deeply understand how the niche regulates hematopoiesis and how niche dysregulation occurs.

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Cold agglutinin disease, one of the serological classifications of immune-mediated hemolytic anemia, is caused by the production of autoantibodies that react with erythrocytes at low temperatures. A captive bottlenose dolphin presented with regenerative and hemolytic anemia. Anticoagulated whole blood was agglutinated at room temperature (approximately 18°C), with reversal of agglutination on warming to 37°C, indicating the presence of cold agglutinin.

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Background: The number of patients with prolonged critical illness (PCI) has been increasing in many countries, and the adrenal gland plays an important role in maintaining homeostasis during PCI. Chronic disease burden is reportedly associated with shorter telomere lengths in human tissues. Telomere shortening in human somatic cells is largely dependent on cell divisions, and critically short telomeres lead to cellular dysfunction and aging.

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Article Synopsis
  • - The study investigates the role of MBTD1, a protein important in hematopoietic stem cells (HSCs), showing it is vital for maintaining HSC quantity and functionality, particularly in fetal development.
  • - Researchers created conditional knockout mice to explore MBTD1's influence on adult HSCs, finding that its absence led to increased HSC numbers but caused defects in stress response and cell cycle regulation.
  • - The findings suggest that MBTD1 helps maintain the quiescence of HSCs by interacting with the FOXO3a protein; restoring FOXO3a in deficient HSCs corrected the observed abnormalities, establishing MBTD1 as key in regulating HSC pool size and health.
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  • Most adult hematopoietic stem cells (HSCs) stay in a quiescent state, and while glycolysis has a payoff phase crucial for HSC function, the role of its preparatory phase is not well understood.
  • This study explores the necessity of both glycolytic phases using key genes Gpi1 and Gapdh; findings reveal that while quiescent HSCs can maintain function despite defects, proliferative HSCs struggle significantly without the payoff phase.
  • The research indicates that quiescent HSCs compensate for glycolytic deficiencies through oxidative phosphorylation (OXPHOS), while proliferative HSCs use the nonoxidative pentose phosphate pathway (PPP) to offset issues in the prepar
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Preculture is indispensable for achieving highly efficient non-homologous end joining (NHEJ)-based genome editing. Here, we present a protocol for optimizing genome editing conditions for murine hematopoietic stem cells (HSCs) and evaluating their function following NHEJ-based genome editing. We describe steps for sgRNA preparation, cell sorting, preculture, and electroporation.

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Garré's osteomyelitis, first described by Carl Garré in 1893, is a type of chronic osteomyelitis accompanied by hyperplastic periostitis. This condition affects relatively young patients and occurs in the fibula, femur, and other long bones as chronic non-purulent sclerosing osteomyelitis. Further, reactive periosteal bone formation develops due to chronic irritation or infection.

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Background: The histology of the cardiac mucosa at the esophagogastric junction (EGJ) at birth is still a controversy. We conducted a histopathological study of the EGJ to clarify the morphology, and to determine the presence or absence of cardiac mucosa at birth.

Subjects: We examined 43 Japanese neonates and infants that are born prematurely or at full term.

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Soft tissue sarcomas (STSs) are a heterogeneous group of tumors that originate from mesenchymal cells. p53 is frequently mutated in human STS. In this study, we found that the loss of p53 in mesenchymal stem cells (MSCs) mainly causes adult undifferentiated soft tissue sarcoma (USTS).

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Autism spectrum disorder (ASD) is caused by combined genetic and environmental factors. Genetic heritability in ASD is estimated as 60-90%, and genetic investigations have revealed many monogenic factors. We analyzed 405 patients with ASD using family-based exome sequencing to detect disease-causing single-nucleotide variants (SNVs), small insertions and deletions (indels), and copy number variations (CNVs) for molecular diagnoses.

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An epitaxial film of YbFeO, a candidate for oxide electronic ferroelectrics, was fabricated on yttrium-stabilized zirconia (YSZ) substrate by magnetron sputtering technique. For the film, second harmonic generation (SHG), and a terahertz radiation signal were observed at room temperature, confirming a polar structure of the film. The azimuth angle dependence of SHG shows four leaves-like profiles and is almost identical to that in a bulk single crystal.

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Oxidative stress (OS) results in many disorders, of which degenerative musculoskeletal conditions are no exception. However, the interaction between OS and ligamentum flavum (LF) hypertrophy in lumbar spinal canal stenosis is not clearly understood. The first research question was whether OS was involved in LF hypertrophy, and the second was whether the antioxidant N-acetylcysteine (NAC) was effective on LF hypertrophy.

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Article Synopsis
  • The study introduces a new platform to investigate hematopoietic stem cell (HSC) quiescence using a combination of special culture conditions and a CRISPR-Cas9 genome editing system tailored for HSCs.
  • It was found that pre-culturing HSCs boosts editing efficiency by aiding the transport of essential components into the cell nucleus.
  • The research indicates that HSCs maintain their traits and remain quiescent better in low-cytokine, low-oxygen environments than in proliferative conditions, even after being edited genetically.
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Cellular senescence caused by oncogenic stimuli is associated with the development of various age-related pathologies through the senescence-associated secretory phenotype (SASP). SASP is mediated by the activation of cytoplasmic nucleic acid sensors. However, the molecular mechanism underlying the accumulation of nucleotide ligands in senescent cells is unclear.

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