28 research outputs found
Functional B-1 progenitor cells are present in the hematopoietic stem cell-deficient embryo and depend on Cbfβ for their development
The fetal liver is a major hematopoietic site containing progenitor cells that give rise to nearly all blood cells, including B-1 cells. Because the fetal liver is not a de novo site of hematopoietic stem cell (HSC) or progenitor-cell emergence, it must be seeded by yolk sac (YS)-derived erythromyeloid progenitors at embryonic day (E) 8.5-E10 and aorta-gonado-mesonephros (AGM)-derived HSCs at E10.5-E11.5. Although the B-1 progenitor cell pool in the fetal liver is considered to be of HSC origin, we have previously proposed that YS-derived B-1 progenitors may also contribute to this pool. Until now, it has been impossible to determine whether HSC-independent B-1 progenitor cells exist in the fetal liver. Here, we demonstrate the presence of transplantable fetal-liver B-1 and marginal zone B progenitor cells in genetically engineered HSC-deficient embryos. HSC-deficient YS and AGM tissues produce B-1 progenitors in vitro and thus may serve as sites of origin for the B-1 progenitors that seed the fetal liver. Furthermore, we have found that core-binding factor beta (Cbfβ) expression is required for fetal-liver B-1 progenitor cell maturation and expansion. Our data provide, to our knowledge, the first evidence for the presence of B-1 progenitor cells in the fetal liver that arise independently of HSCs and implicate Cbfβ as a critical molecule in the development of this lineage
Direct 2D-to-3D transformation of pen drawings
Pen drawing is a method that allows simple, inexpensive, and intuitive two-dimensional (2D) fabrication. To integrate such advantages of pen drawing in fabricating 3D objects, we developed a 3D fabrication technology that can directly transform pen-drawn 2D precursors into 3D geometries. 2D-to-3D transformation of pen drawings is facilitated by surface tension-driven capillary peeling and floating of dried ink film when the drawing is dipped into an aqueous monomer solution. Selective control of the floating and anchoring parts of a 2D precursor allowed the 2D drawing to transform into the designed 3D structure. The transformed 3D geometry can then be fixed by structural reinforcement using surface-initiated polymerization. By transforming simple pen-drawn 2D structures into complex 3D structures, our approach enables freestyle rapid prototyping via pen drawing, as well as mass production of 3D objects via roll-to-roll processing
Functional analysis of murine CD43 shedding : a role for the CD43 cytoplasmic tail in nuclear signalling
CD43, a representative of the leukocyte mucin family proteins, is a transmembrane protein highly expressed on most lymphohemopoietic cells and is believed to play a role in the regulation of leukocyte activation and/or migration. CD43 was shown to be proteolytically shed from human cells and high concentrations of soluble CD43 have been found in human plasma. The biological significance of CD43 shedding however remains enigmatic.
To study the functional significance of CD43 shedding, we initiated our study by investigating whether CD43 shedding also occurs in the murine system and confirmed using flow cytometry, Western blot and ELISA techniques that murine CD43 is cleaved from the cell surface as is observed in the human system. To examine the biological significance of CD43 shedding, we designed and constructed non-sheddable forms of murine CD43. Ectopic expression of non-sheddable CD43 molecules in primary CD43 deficient bone marrow cells showed that these CD43 mutants have serious negative impacts on cell viability, revealing CD43 shedding as an essential process and implying that the CD43 mutants interfered with intracellular signaling processes. Our data support the hypothesis that CD43 ectodomain shedding is a requirement for release of the cytoplasmic domain and its translocation to the nucleus. In support of our hypothesis, we confirmed that the CD43 cytoplasmic domain is localized in the nucleus and is modified by SUMO (small ubiquitin-like modifier) peptides. In an attempt to determine the functional significance of CD43 nuclear translocation and SUMO modification, we examined nuclei from hemopoietic cells more closely and observed that the CD43 cytoplasmic tail is localized in a subnuclear structure called promyelocytic nuclear bodies, which control many nuclear functions including apoptosis. Consistent with this observation we find that leukocytes from CD43 deficient mice have an increased apoptotic response upon growth factor withdrawal. We conclude that nuclear translocation of the CD43 cytoplasmic tail serves to control the apoptotic response in leukocytes and that CD43 functions as an anti-apoptotic molecule.Medicine, Faculty ofMedicine, Department ofExperimental Medicine, Division ofGraduat
Runx-mediated regulation of CCL5 via antagonizing two enhancers influences immune cell function and anti-tumor immunity.
The Roles of RUNX Proteins in Lymphocyte Function and Anti-Tumor Immunity
The Runt-related transcription factor (RUNX) family of proteins are crucial for many developmental and immuno-physiological processes. Their importance in cellular and tissue development has been repeatedly demonstrated as they are often found mutated and implicated in tumorigenesis. Most importantly, RUNX have now emerged as critical regulators of lymphocyte function against pathogenic infections and tumorigenic cells, the latter has now revolutionized our current understandings as to how RUNX proteins contribute to control tumor pathogenicity. These multifunctional roles of RUNX in mammalian immune responses and tissue homeostasis have led us to appreciate their value in controlling anti-tumor immune responses. Here, we summarize and discuss the role of RUNX in regulating the development and function of lymphocytes responding to foreign and tumorigenic threats and highlight their key roles in anti-tumor immunity
Réception du Salon de 1874 et de la première exposition des impressionnistes à Paris en 1874: Exploration d'un corpus de comptes-rendus des expositions
International audienceA l'occasion du 150e anniversaire du mouvement impressionniste en 2024, notre communication propose une approche numérique appliquée à l'étude de la critique de l'art en 1874 à Paris, à travers l'étude de deux expositions majeures : le Salon et l'exposition des peintres impressionnistes. Notre démarche commence par l'établissement d'un corpus inédit en XML-TEI, suivi de la création d'un sous-corpus focalisé sur quatre critiques parmi les plus importants, afin de mener une analyse détaillée de certains artistes. Notre analyse est effectuée à travers l'exploration des opinions positives et négatives envers ces artistes et leurs œuvres, en s'appuyant sur des techniques de fouille de textes et d'annotation automatique des sentiments. À moyen terme, nous envisageons une exploration raffinée de catégories sémantiques, croisée avec une analyse thématique approfondie du corpus
Réception du Salon de 1874 et de la première exposition des impressionnistes à Paris en 1874: Exploration d'un corpus de comptes-rendus des expositions
International audienceA l'occasion du 150e anniversaire du mouvement impressionniste en 2024, notre communication propose une approche numérique appliquée à l'étude de la critique de l'art en 1874 à Paris, à travers l'étude de deux expositions majeures : le Salon et l'exposition des peintres impressionnistes. Notre démarche commence par l'établissement d'un corpus inédit en XML-TEI, suivi de la création d'un sous-corpus focalisé sur quatre critiques parmi les plus importants, afin de mener une analyse détaillée de certains artistes. Notre analyse est effectuée à travers l'exploration des opinions positives et négatives envers ces artistes et leurs œuvres, en s'appuyant sur des techniques de fouille de textes et d'annotation automatique des sentiments. À moyen terme, nous envisageons une exploration raffinée de catégories sémantiques, croisée avec une analyse thématique approfondie du corpus
Réception du Salon de 1874 et de la première exposition des impressionnistes à Paris en 1874: Exploration d'un corpus de comptes-rendus des expositions
International audienceA l'occasion du 150e anniversaire du mouvement impressionniste en 2024, notre communication propose une approche numérique appliquée à l'étude de la critique de l'art en 1874 à Paris, à travers l'étude de deux expositions majeures : le Salon et l'exposition des peintres impressionnistes. Notre démarche commence par l'établissement d'un corpus inédit en XML-TEI, suivi de la création d'un sous-corpus focalisé sur quatre critiques parmi les plus importants, afin de mener une analyse détaillée de certains artistes. Notre analyse est effectuée à travers l'exploration des opinions positives et négatives envers ces artistes et leurs œuvres, en s'appuyant sur des techniques de fouille de textes et d'annotation automatique des sentiments. À moyen terme, nous envisageons une exploration raffinée de catégories sémantiques, croisée avec une analyse thématique approfondie du corpus
Impact of particulate microplastics generated from polyethylene terephthalate on gut pathology and immune microenvironments
Summary: Environmental microplastics have emerged as a critical issue in maintaining the planetary ecosystem. In this study, we generated particulate microplastics from polyethylene terephthalate (PM-PET) and investigated their impact in the gut by using mouse models and implementing histological examinations, as well as multi-omics analysis for colonic immune cells and microbiota. As a result, histological approaches showed that chronic and physiological low dose exposure of PM-PET did not affect intestinal pathology and mucin barriers, respectively. Moreover, immunohistochemical analysis demonstrated that the numbers of T cells, B cells, macrophages, and granulocytes were not affected by the exposure to PM-PET. However, RNA-seq analysis revealed that PM-PET had a substantial impact on the transcriptome in gut immune cells and their metabolisms, while 16s rRNA metagenomic analysis showed that the composition of microbiota was modestly affected. These results suggest an unexpected role played by the PM-PET in affecting gut immune homeostasis without detectable inflammation
Prediction of Concrete Fragments Amount and Travel Distance under Impact Loading Using Deep Neural Network and Gradient Boosting Method
In the present study, the amount of fragments generated and their travel distances due to vehicle collision with concrete median barrier (CMB) was analyzed and predicted. In this regard, machine learning was applied to the results of numerical analysis, which were developed by comparing with field test. The numerical model was developed using smoothed particle hydrodynamics (SPH). SPH is a mesh-free method that can be used to predict the amount of fragments and their travel distances from concrete structures under impact loading. In addition, deep neural network (DNN) and gradient boosting machine (GBM) were also employed as machine learning methods. In this study, the results of DNN, GBM, and numerical analysis were then compared with the conducted field test. Such comparisons revealed that numerical analysis generated lower error than both DNN and GBM. When prediction results of both the amount of fragments and their travel distances were considered, the result of DNN showed smaller errors than that of GBM. Therefore, in studies where machine learning is used to predict the amount of fragments and their travel distances, careful selection of an appropriate method from the various available machine learning methods such as DNN, GBM, and random forest is absolutely important