Degenerative and regenerative features of myofibers differ among skeletal muscles in a murine model of muscular dystrophy

Skeletal muscle myofibers constantly undergo degeneration and regeneration. Histopathological features of 6 skeletal muscles (cranial tibial [CT], gastrocnemius, quadriceps femoris, triceps brachii [TB], lumbar longissimus muscles, and costal part of the diaphragm [CPD]) were compared using C57BL/10ScSn-Dmd (mdx) (mdx) mice, a model for muscular dystrophy versus control, C57BL/10 mice. Body weight and skeletal muscle mass were lower in mdx mice than the control at 4 weeks of age; these results were similar at 6-30 weeks. Additionally, muscular lesions were observed in all examined skeletal muscles in mdx mice after 4 weeks, but none were noted in the controls. Immunohistochemical staining revealed numerous paired box 7-positive satellite cells surrounding the embryonic myosin heavy chain-positive regenerating myofibers, while the number of the former and staining intensity of the latter decreased as myofiber regeneration progressed. Persistent muscular lesions were observed in skeletal muscles of mdx mice between 4 and 14 weeks of age, and normal myofibers decreased with age. Number of muscular lesions was lowest in CPD at all ages examined, while the ratio of normal myofibers was lowest in TB at 6 weeks. In CT, TB, and CPD, Iba1-positive macrophages, the main inflammatory cells in skeletal muscle lesions, showed a significant positive correlation with the appearance of regenerating myofibers. Additionally, B220-positive B-cells showed positive and negative correlation with regenerating and regenerated myofibers, respectively. Our data suggest that degenerative and regenerative features of myofibers differ among skeletal muscles and that inflammatory cells are strongly associated with regenerative features of myofibers in mdx mice

Pathogenetic role of an autoimmune susceptibility locus derived from MRL/MpJ strain chromosome 1 in chronic pancreas inflammation

We examined the role of Mag, an autoimmune　susceptibility locus encoded by the telomeric region of MRL/MpJ mouse chromosome 1, in the pathogenesis of autoimmune exocrinopathy. At nine to 12 months of age, strain-specific differences were observed in the pancreas of the animals. B- and T-cell-containing periductal/perivascular cell infiltrations in the pancreases of MRL/MpJ and B6.MRLc1 congenic C57BL/6-background Mag-carrying strains were more severe than were those of C57BL/6. Pancreatic periductal/perivascular cell infiltration was observed frequently in A/J, AKR/N, B6.MRLc1, C57BL/6, and MRL/MpJ, moderately in DBA/1 and DBA/2, and rarely in BALB/c and C3H/He strains. Females tended to have greater pancreatic periductal/perivascular cell infiltration than males. C57BL/6 mice possessed defined borders between cell infiltrations and acini, but borders were indistinct in MRL/MpJ and B6.MRLc1 mice. We attributed this to the invasion of inflammatory cells between each acinus and the disruption of acinar cells around cell infiltrations in the latter strains. No strain-specific differences were observed in the appearance of fibrotic lesions and high endothelial venules in the cell infiltrates. The levels of serum anti-dsDNA antibodies and amylase, and mRNA expression of tumor necrosis factor- and Fc gamma receptor III (encoded on Mag) in the pancreases, were elevated in MRL/MpJ- and B6.MRLc1-strain mice relative to C57BL/6. These results emphasized the crucial roles of Mag in the molecular and genetic pathogenesis of autoimmune-mediated pancreatitis

Morphological characteristics observed during early follicular development in perinatal MRL/MpJ mice

In perinatal mice, the ovary undergoes drastic　morphological changes, as clusters of oocytes called nests break into smaller cysts and subsequently form individual follicles. We studied perinatal oocyte development in MRL/MpJ mice, and compared it to that observed in C57BL/6 mice between embryonic day 18.5 and postnatal day 4. Throughout the observation period, compared to C57BL/6 mice, MRL/MpJ mice displayed significantly fewer oocytes in their ovaries.　Morphologically, there were no clear differences　between the strains at embryonic day 18.5. However, the beginning of folliculogenesis, as evidenced by the expression of NOBOX oogenesis homeobox (Nobox)　transcript and protein, was more enhanced in MRL/MpJ mice than in C57BL/6 mice at embryonic day 18.5 and postnatal day 0. In addition, developed follicles were more frequently observed in MRL/MpJ mice than in　C57BL/6 mice between postnatal days 0 and 4. In　conclusion, the oocyte development during nest　breakdown and folliculogenesis was accelerated in MRL/MpJ mice when compared to that observed in C57BL/6 mice

Quantum AI simulator using a hybrid CPU–FPGA approach

Abstract The quantum kernel method has attracted considerable attention in the field of quantum machine learning. However, exploring the applicability of quantum kernels in more realistic settings has been hindered by the number of physical qubits current noisy quantum computers have, thereby limiting the number of features encoded for quantum kernels. Hence, there is a need for an efficient, application-specific simulator for quantum computing by using classical technology. Here we focus on quantum kernels empirically designed for image classification and demonstrate a field programmable gate arrays (FPGA) implementation. We show that the quantum kernel estimation by our heterogeneous CPU–FPGA computing is 470 times faster than that by a conventional CPU implementation. The co-design of our application-specific quantum kernel and its efficient FPGA implementation enabled us to perform one of the largest numerical simulations of a gate-based quantum kernel in terms of features, up to 780-dimensional features. We apply our quantum kernel to classification tasks using the Fashion-MNIST dataset and show that our quantum kernel is comparable to Gaussian kernels with the optimized hyperparameter

Overexpression of Toll-like receptor 8 correlates with the progression of podocyte injury in murine autoimmune glomerulonephritis

Members of the Toll-like receptor (TLR) family serve as pathogen sensors and participate in local autoimmune responses. This study found a correlation between glomerular injury and TLR expression by analysing BXSB/MpJ-Yaa (BXSB-Yaa) lupus model mice. In isolated glomeruli, the mRNA expression of several TLRs was higher in BXSB-Yaa mice than in healthy control BXSB mice. In particular, the expression of Tlr8 and its downstream cytokines was markedly increased. In mouse kidneys, TLR8 protein and mRNA localized to podocytes, and TLR8 protein expression in the glomerulus was higher in BXSB-Yaa mice than in BXSB mice. In BXSB-Yaa mice, the glomerular levels of Tlr8 mRNA negatively correlated with the glomerular levels of podocyte functional markers (Nphs1, Nphs2, and Synpo) and positively correlated with urinary albumin levels. Furthermore, the glomerular and serum levels of miR-21, a putative microRNA ligand of TLR8, were higher in BXSB-Yaa mice than in BXSB mice. The urinary levels of Tlr8 mRNA were also higher in BXSB-Yaa mice than in BXSB mice. In conclusion, the overexpression of TLR8 correlates with the progression of podocyte injury in glomerulonephritis. Thus, altered levels of urinary Tlr8 mRNA might reflect podocyte injury

Relationship between Numerous Mast Cells and Early Follicular Development in Neonatal MRL/MpJ Mouse Ovaries

In the neonatal mouse ovary, clusters of oocytes called nests break into smaller cysts and subsequently form individual follicles. During this period, we found numerous mast cells in the ovary of MRL/MpJ mice and investigated their appearance and morphology with follicular development. The ovarian mast cells, which were already present at postnatal day 0, tended to localize adjacent to the surface epithelium. Among 11 different mouse strains, MRL/MpJ mice possessed the greatest number of ovarian mast cells. Ovarian mast cells were also found in DBA/1, BALB/c, NZW, and DBA/2 mice but rarely in C57BL/6, NZB, AKR, C3H/He, CBA, and ICR mice. The ovarian mast cells expressed connective tissue mast cell markers, although mast cells around the surface epithelium also expressed a mucosal mast cell marker in MRL/MpJ mice. Some ovarian mast cells migrated into the oocyte nests and directly contacted the compressed and degenerated oocytes. In MRL/MpJ mice, the number of oocytes in the nest was significantly lower than in the other strains, and the number of oocytes showed a positive correlation with the number of ovarian mast cells. The gene expression of a mast cell marker also correlated with the expression of an oocyte nest marker, suggesting a link between the appearance of ovarian ? 4mast cells and early follicular development. Furthermore, the expression of follicle developmental markers was significantly higher in MRL/MpJ mice than in C57BL/6 mice. These results indicate that the appearance of ovarian mast cells is a unique phenotype of neonatal MRL/MpJ mice, and that ovarian mast cells participate in early follicular development, especially nest breakdown