The first case of recurrent ultra late onset group B streptococcal sepsis in a 3-year-old child

AbstractGroup B streptococcus (GBS) is a commonly recognized cause of sepsis and meningitis in neonatal and young infants. Invasive GBS infection is classified into early onset GBS disease (EOD, day 0–6), late onset GBS disease (LOD, day 7–89) and ultra late onset GBS disease (ULOD, after 3 months of age). ULOD is uncommon and recurrence is especially rare. We present the first recurrent case of ULOD GBS sepsis in 3-year-old girl with a past medical history of hydrops fetalis and thoracic congenital lymphatic dysplasia. The first episode presented as sepsis at 2 years 8 months of age. The second episode occurred as sepsis with encephalopathy at 3 years 1 months of age. During each episode, the patient was treated using intravenous antimicrobials and her condition improved. Serotype examination was not performed in the first episode, but GBS type V was serotyped in the second episode. ULOD over 1year of age is quite rare and may recur

The role played by cell-substrate interactions in the pathogenesis of osteoclast-mediated peri-implant osteolysis

Prosthetic wear debris-induced peri-implant osteolysis is a major cause of aseptic loosening after total joint replacement. In this condition, wear particles released from the implant components induce a granulomatous inflammatory reaction at the interface between implant and adjacent bone, leading to progressive bone resorption and loss of fixation. The present study was undertaken to characterize definitively the phenotype of osteoclast-like cells associated with regions of peri-implant focal bone resorption and to compare the phenotypic features of these cells with those of mononucleated and multinucleated cells associated with polyethylene wear particles. Peri-implant tissues were obtained from patients undergoing hip revision surgery for aseptic loosening after total joint replacement. Cells were examined for the expression of several markers associated with the osteoclast phenotype using immunohistochemistry, histochemistry, and/or in situ hybridization. CD68 protein, a marker expressed by multiple macrophage lineage cell types, was detected in mononucleated and multinucleated cells associated with polyethylene particles and the bone surface. Cathepsin K and tartrate-resistant acid phosphatase were expressed highly in both mononucleated and multinucleated cells associated with the bone surface. Levels of expression were much lower in cells associated with polyethylene particles. High levels of β(3 )integrin protein were detected in cells in contact with bone. Multinucleated cells associated with polyethylene particles exhibited faint positive staining. Calcitonin receptor mRNA expression was detected solely in multinucleated cells present in resorption lacunae on the bone surface and was absent in cells associated with polyethylene particles. Our findings provide further evidence that cells expressing the full repertoire of osteoclast phenotypic markers are involved in the pathogenesis of peri-implant osteolysis after total joint replacement. They also demonstrate that foreign body giant cells, although believed to be phenotypically and functionally distinct from osteoclasts, express many osteoclast-associated genes and gene products. However, the levels and patterns of expression of these genes in the two cell types differ. We speculate that, in addition to the role of cytokines and growth factors, the substrate with which these cells interact plays a critical role in their differential phenotypic and functional properties

自閉症死後脳縫線核メチル化状態の網羅的解析

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Forkhead-Associated Domain of Yeast Xrs2, a Homolog of Human Nbs1, Promotes Nonhomologous End Joining Through Interaction With a Ligase IV Partner Protein, Lif1

DNA double-strand breaks (DSB) are repaired through two different pathways, homologous recombination (HR) and nonhomologous end joining (NHEJ). Yeast Xrs2, a homolog of human Nbs1, is a component of the Mre11-Rad50-Xrs2 (MRX) complex required for both HR and NHEJ. Previous studies showed that the N-terminal forkhead-associated (FHA) domain of Xrs2/Nbs1 in yeast is not involved in HR, but is likely to be in NHEJ. In this study, we showed that the FHA domain of Xrs2 plays a critical role in efficient DSB repair by NHEJ. The FHA domain of Xrs2 specifically interacts with Lif1, a component of the ligase IV complex, Dnl4-Nej1-Lif1 (DNL). Lif1, which is phosphorylated in vivo, contains two Xrs2-binding regions. Serine 383 of Lif1 plays an important role in the interaction with Xrs2 as well as in NHEJ. Interestingly, the phospho-mimetic substitutions of serine 383 enhance the NHEJ activity of Lif1. Our results suggest that the phosphorylation of Lif1 at serine 383 is recognized by the Xrs2 FHA domain, which in turn may promote recruitment of the DNL complex to DSB for NHEJ. The interaction between Xrs2 and Lif1 through the FHA domain is conserved in humans; the FHA domain Nbs1 interacts with Xrcc4, a Lif1 homolog of human

Suppression of homologous recombination by anti-recombinase

本研究では、申請者の発見した新規相同組換え抑制因子FIGNL1の機能を明らかにすることを目指して研究を行った。また、相同組換えの抑制の必要性についても理解できると期待して研究を進めた。作製したヒトFIGNL1ノックアウト細胞では、染色体分配の異常と染色体上へのRAD51の過剰な蓄積が見られた。実際に、RAD51を阻害することで、これらの欠損を抑制されたことから、RAD51が染色体上に蓄積することで、染色体分配を阻害している可能性を示している。本研究では、さらにFIGNL1がRAD51の蓄積をどのように抑制しているかについても明らかにすることができた。Homologous recombination (HR) is essential mechanism to maintain genome stability. Homology search and strand invasion steps in HR are catalyzed by RAD51 protein. Formation of RAD51 filament on ssDNA is necessary to execute proper HR and restart of DNA replication forks, while inappropriate RAD51 filament formation causes genome instability. Hence, RAD51 filament formation is tightly suppressed by anti-recombinases, which promote the dissociation of RAD51. However, the mechanisms underlying genome instability caused by inappropriate RAD51 assembly and the suppression by anti-recombinases remain largely unknown. Here, we report a role for the human AAA+ ATPase, FIGNL1 as a novel anti-recombinase. FIGNL1-deficient cells show the excessive RAD51 recruitment. RAD51 filaments persist and cause defects in chromosome segregation. Our data suggest that recombination intermediates caused by inappropriate RAD51 assembly prevent chromosome segregation and induce genome instability.研究分野：相同組換

Fundamental study on countermeasures against subharmonic vibration of order 1/2 in automatic transmissions for cars

In automatic transmissions for cars, a damper is installed in the lock-up clutch to absorb torsional vibrations caused by combustion in the engine. Although a damper with low stiffness reduces the torsional vibration, low-stiffness springs are difficult to use because of space limitations. To address this problem, dampers have been designed using a piecewise-linear spring having three different stages of stiffness. However, a nonlinear subharmonic vibration of order 1/2 occurs because of the nonlinearity of the piecewise-linear spring in the damper. In this study, we experimentally and analytically examined a countermeasure against the subharmonic vibration by increasing the stages of the piecewise-linear spring using the one-degree-of-freedom system model. We found that the gap between the switching points of the piecewise-linear spring was the key to vibration reduction. The experimental results agreed with results of the numerical analyses

Fundamental study on countermeasures against subharmonic vibration of order 1/2 in automatic transmissions for cars

In automatic transmissions for cars, a damper is installed in the lock-up clutch to absorb torsional vibrations caused by combustion in the engine. Although a damper with low stiffness reduces the torsional vibration, low-stiffness springs are difficult to use because of space limitations. To address this problem, dampers have been designed using a piecewise-linear spring having three different stages of stiffness. However, a nonlinear subharmonic vibration of order 1/2 occurs because of the nonlinearity of the piecewise-linear spring in the damper. In this study, we experimentally and analytically examined a countermeasure against the subharmonic vibration by increasing the stages of the piecewise-linear spring using the one-degree-of-freedom system model. We found that the gap between the switching points of the piecewise-linear spring was the key to vibration reduction. The experimental results agreed with results of the numerical analyses