Higgs response and pair condensation energy in superfluid nuclei

The pairing correlation in nuclei causes a characteristic excitation, known as the pair vibration, which is populated by the pair transfer reactions. Here we introduce a new method of characterizing the pair vibration by employing an analogy to the Higgs mode, which emerges in infinite superconducting/superfluid systems as a collective vibrational mode associated with the amplitude oscillation of the Cooper pair condensate. The idea is formulated by defining a pair-transfer probe, the Higgs operator, and then describing the linear response and the strength function to this probe. We will show that the pair condensation energy in nuclei can be extracted with use of the strength sum and the static polarizability of the Higgs response. In order to demonstrate and validate the method, we perform for Sn isotopes numerical analysis based the quasi-particle random phase approximation to the Skyrme-Hartree-Fock-Bogoliubov model. We discuss a possibility to apply this new scheme to pair transfer experiment.Comment: 31 pages, 9 figure

Generation of monkey iPS cell-derived cartilage lacking MHC class I molecules on the cell surface

Multiple immune reactions when transplanting cartilage into monkeys. 京都大学プレスリリース. 2021-07-07.Due to the poor capacity for articular cartilage to regenerate, its damage tends to result in progressively degenerating conditions such as osteoarthritis. To repair the damage, the transplantation of allogeneic human induced pluripotent stem cell (iPSC)-derived cartilage is being considered. However, although allogeneic cartilage transplantation is effective, immunological reactions can occur. One hypothetical solution is to delete the expression of MHC class I molecules in order to reduce the immunological reactions. For this purpose, we deleted the β2 microglobulin (B2M) gene in a cynomolgus monkey (crab-eating monkey (Macaca fascicularis)) iPS cells (cyiPSCs) to obtain B2M⁻/⁻ cyiPSCs using the CRISPR/Cas9 system. Western blot analysis confirmed B2M⁻/⁻ cyiPSCs lacked B2M protein, which is necessary for MHC class I molecules to be transported to and expressed on the cell surface by forming multimers with B2M. Flow cytometry analysis revealed no B2M⁻/⁻ cyiPSCs expressed MHC class I molecules on their surface. The transplantation of B2M⁻/⁻ cyiPSCs in immunodeficient mice resulted in teratoma that contained cartilage, indicating that the lack of MHC class I molecules on the cell surface affects neither the pluripotency nor the chondrogenic differentiation capacity of cyiPSCs. By modifying the chondrogenic differentiation protocol for human iPSCs, we succeeded at differentiating B2M⁺/⁺ and B2M⁻/⁻ cyiPSCs toward chondrocytes followed by cartilage formation in vitro, as indicated by histological analysis showing that B2M⁺/⁺ and B2M⁻/⁻ cyiPSC-derived cartilage were positively stained with safranin O and expressed type II collagen. Flow cytometry analysis confirmed that MHC class I molecules were not expressed on the cell surface of B2M⁻/⁻ chondrocytes isolated from B2M⁻/⁻ cyiPSC-derived cartilage. An in vitro mixed lymphocyte reaction assay showed that neither B2M⁺/⁺ nor B2M⁻/⁻ cyiPSC-derived cartilage cells stimulated the proliferation of allogeneic peripheral blood mononuclear cells. On the other hand, osteochondral defects in monkey knee joints that received allogeneic transplantations of cyiPSC-derived cartilage showed an accumulation of leukocytes with more natural killer (NK) cells around B2M⁻/⁻ cyiPSC-derived cartilage than B2M⁺/⁺ cartilage, suggesting complex mechanisms in the immune reaction of allogeneic cartilage transplanted in osteochondral defects in vivo

Generation of Monkey Induced Pluripotent Stem Cell-Derived Cartilage Lacking Major Histocompatibility Complex Class I Molecules on the Cell Surface

Due to the poor capacity for articular cartilage to regenerate, its damage tends to result in progressively degenerating conditions such as osteoarthritis. To repair the damage, the transplantation of allogeneic human induced pluripotent stem cell (iPSC)-derived cartilage is being considered. However, although allogeneic cartilage transplantation is effective, immunological reactions can occur. One hypothetical solution is to delete the expression of major histocompatibility complex (MHC) class I molecules to reduce the immunological reactions. For this purpose, we deleted the β2 microglobulin (B2M) gene in a cynomolgus monkey (crab-eating monkey [Macaca fascicularis]) iPS cells (cyiPSCs) to obtain B2M−/− cyiPSCs using the CRISPR/Cas9 system. Western blot analysis confirmed B2M−/− cyiPSCs lacked B2M protein, which is necessary for MHC class I molecules to be transported to and expressed on the cell surface by forming multimers with B2M. Flow cytometry analysis revealed no B2M−/− cyiPSCs expressed MHC class I molecules on their surface. The transplantation of B2M−/− cyiPSCs in immunodeficient mice resulted in teratoma that contained cartilage, indicating that the lack of MHC class I molecules on the cell surface affects neither the pluripotency nor the chondrogenic differentiation capacity of cyiPSCs. By modifying the chondrogenic differentiation protocol for human iPSCs, we succeeded at differentiating B2M+/+ and B2M−/− cyiPSCs toward chondrocytes followed by cartilage formation in vitro, as indicated by histological analysis showing that B2M+/+ and B2M−/− cyiPSC-derived cartilage were positively stained with safranin O and expressed type II collagen. Flow cytometry analysis confirmed that MHC class I molecules were not expressed on the cell surface of B2M−/− chondrocytes isolated from B2M−/− cyiPSC-derived cartilage. An in vitro mixed lymphocyte reaction assay showed that neither B2M+/+ nor B2M−/− cyiPSC-derived cartilage cells stimulated the proliferation of allogeneic peripheral blood mononuclear cells. On the contrary, osteochondral defects in monkey knee joints that received allogeneic transplantations of cyiPSC-derived cartilage showed an accumulation of leukocytes with more natural killer cells around B2M−/− cyiPSC-derived cartilage than B2M+/+ cartilage, suggesting complex mechanisms in the immune reaction of allogeneic cartilage transplanted in osteochondral defects in vivo.Okutani Y., Abe K., Yamashita A., et al. Generation of Monkey Induced Pluripotent Stem Cell-Derived Cartilage Lacking Major Histocompatibility Complex Class I Molecules on the Cell Surface. Tissue Engineering - Part A 28, 94 (2022); https://doi.org/10.1089/ten.tea.2021.0053

High glucose-induced apoptosis in human coronary artery endothelial cells involves up-regulation of death receptors

<p>Abstract</p> <p>Background</p> <p>High glucose can induce apoptosis in vascular endothelial cells, which may contribute to the development of vascular complications in diabetes. We evaluated the role of the death receptor pathway of apoptotic signaling in high glucose-induced apoptosis in human coronary artery endothelial cells (HCAECs).</p> <p>Methods</p> <p>HCAECs were treated with media containing 5.6, 11.1, and 16.7 mM of glucose for 24 h in the presence or absence of tumor necrosis factor (TNF)-α. For detection of apoptosis, DNA fragmentation assay was used. HCAEC expression of death receptors were analyzed by the PCR and flow cytometry methods. Also, using immunohistochemical techniques, coronary expression of death receptors was assessed in streptozotocin-nicotinamide-induced type 2 diabetic mice.</p> <p>Results</p> <p>Exposure of HCAECs to high glucose resulted in a significant increase in TNF-R1 and Fas expression, compared with normal glucose. High glucose increased TNF-α production by HCAECs and exogenous TNF-α up-regulated TNF-R1 and Fas expression in HCAECs. High glucose-induced up-regulation of TNF-R1 and Fas expression was undetectable in the presence of TNF-α. Treatment with TNF-R1 neutralizing peptides significantly inhibited high glucose-induced endothelial cell apoptosis. Type 2 diabetic mice displayed appreciable expression of TNF-R1 and Fas in coronary vessels.</p> <p>Conclusions</p> <p>In association with increased TNF-α levels, the death receptors, TNF-R1 and Fas, are up-regulated in HCAECs under high glucose conditions, which could in turn play a role in high glucose-induced endothelial cell apoptosis.</p

Engraftment of allogeneic iPS cell-derived cartilage organoid in a primate model of articular cartilage defect

Induced pluripotent stem cells (iPSCs) are a promising resource for allogeneic cartilage transplantation to treat articular cartilage defects that do not heal spontaneously and often progress to debilitating conditions, such as osteoarthritis. However, to the best of our knowledge, allogeneic cartilage transplantation into primate models has never been assessed. Here, we show that allogeneic iPSC-derived cartilage organoids survive and integrate as well as are remodeled as articular cartilage in a primate model of chondral defects in the knee joints. Histological analysis revealed that allogeneic iPSC-derived cartilage organoids in chondral defects elicited no immune reaction and directly contributed to tissue repair for at least four months. iPSC-derived cartilage organoids integrated with the host native articular cartilage and prevented degeneration of the surrounding cartilage. Single-cell RNA-sequence analysis indicated that iPSC-derived cartilage organoids differentiated after transplantation, acquiring expression of PRG4 crucial for joint lubrication. Pathway analysis suggested the involvement of SIK3 inactivation. Our study outcomes suggest that allogeneic transplantation of iPSC-derived cartilage organoids may be clinically applicable for the treatment of patients with chondral defects of the articular cartilage; however further assessment of functional recovery long term after load bearing injuries is required

Engraftment of allogeneic iPS cell-derived cartilage organoid in a primate model of articular cartilage defect

Induced pluripotent stem cells (iPSCs) are a promising resource for allogeneic cartilage transplantation to treat articular cartilage defects that do not heal spontaneously and often progress to debilitating conditions, such as osteoarthritis. However, to the best of our knowledge, allogeneic cartilage transplantation into primate models has never been assessed. Here, we show that allogeneic iPSC-derived cartilage organoids survive and integrate as well as are remodeled as articular cartilage in a primate model of chondral defects in the knee joints. Histological analysis revealed that allogeneic iPSC-derived cartilage organoids in chondral defects elicited no immune reaction and directly contributed to tissue repair for at least four months. iPSC-derived cartilage organoids integrated with the host native articular cartilage and prevented degeneration of the surrounding cartilage. Single-cell RNA-sequence analysis indicated that iPSC-derived cartilage organoids differentiated after transplantation, acquiring expression of PRG4 crucial for joint lubrication. Pathway analysis suggested the involvement of SIK3 inactivation. Our study outcomes suggest that allogeneic transplantation of iPSC-derived cartilage organoids may be clinically applicable for the treatment of patients with chondral defects of the articular cartilage; however further assessment of functional recovery long term after load bearing injuries is required.Abe K., Yamashita A., Morioka M., et al. Engraftment of allogeneic iPS cell-derived cartilage organoid in a primate model of articular cartilage defect. Nature Communications 14, 804 (2023); https://doi.org/10.1038/s41467-023-36408-0

Usefulness of the Multimodal Fusion Image for Visualization of Deep Sylvian Veins

The preoperative assessment of cerebral veins is important to avoid unexpected cerebral venous infarction in the neurosurgical setting. However, information is particularly limited regarding deep Sylvian veins, which occasionally disturb surgical procedures for cerebral anterior circulation aneurysms. The predictability of detecting deep Sylvian veins and their tributaries using a modern multimodal fusion image was aimed to be evaluated. Moreover, 51 patients who underwent microsurgery for unruptured cerebral aneurysms with Sylvian fissure dissection were retrospectively reviewed. The visualization of the four components of the deep Sylvian veins in conventional computed tomography (CT) venography and multimodal fusion images was evaluated. To compare the detection accuracy among these radiological images, the sensitivity and specificity for the detection of each of the four venous structures were calculated in comparison with those of intraoperative inspections. The kappa coefficients were also measured and the inter-rater agreement for each venous structure in each radiological image was examined. In all veins, the multimodal fusion image exhibited a high detection rate without statistical difference from intraoperative inspections (P = 1.0). However, CT venography exhibited a low detection rate with a significant difference from intraoperative inspections in the common vertical trunk (P = 0.006) and attached vein (P = 0.008). The kappa coefficients of the fusion image ranged from 0.73 to 0.91 and were superior to those of CT venography for all venous structures. This is the first report to indicate the usefulness of a multimodal fusion image in evaluating deep Sylvian veins, especially for the detection of nontypical, relatively small veins with large individual variability.博士（医学）・甲第864号・令和5年3月15

Rre37 stimulates accumulation of 2-oxoglutarate and glycogen under nitrogen starvation in Synechocystis sp. PCC 6803

AbstractRre37 (sll1330) in a cyanobacterium Synechocystis sp. PCC 6803 acts as a regulatory protein for sugar catabolic genes during nitrogen starvation. Low glycogen accumulation in Δrre37 was due to low expression of glycogen anabolic genes. In addition to low 2-oxoglutarate accumulation, normal upregulated expression of genes encoding glutamate synthases (gltD and gltB) as well as accumulation of metabolites in glycolysis (fructose-6-phosphate, fructose-1,6-bisphosphate, and glyceraldehyde-3-phosphate) and tricarboxylic acid (TCA) cycle (oxaloacetate, fumarate, succinate, and aconitate) were abolished by rre37 knockout. Rre37 regulates 2-oxoglutarate accumulation, glycogen accumulation through expression of glycogen anabolic genes, and TCA cycle metabolites accumulation