Oscillation dynamics underlie functional switching of NF-κB for B-cell activation.

Transcription factor nuclear factor kappa B (NF-κB) shows cooperative switch-like activation followed by prolonged oscillatory nuclear translocation in response to extracellular stimuli. These dynamics are important for activation of the NF-κB transcriptional machinery, however, NF-κB activity regulated by coordinated actions of these dynamics has not been elucidated at the system level. Using a variety of B cells with artificially rewired NF-κB signaling networks, we show that oscillations and switch-like activation of NF-κB can be dissected and that, under some conditions, these two behaviors are separated upon antigen receptor activation. Comprehensive quantitative experiments and mathematical analysis showed that the functional role of switch activation in the NF-κB system is to overcome transient IKK (IκB kinase) activity to amplify nuclear translocation of NF-κB, thereby inducing the prolonged NF-κB oscillatory behavior necessary for target gene expression and B-cell activation

Physics of Magnetopause Reconnection: A Study of the Combined Effects of Density Asymmetry, Velocity Shear, and Guide Field

Magnetopause reconnection would be characterized by the density jump across the current sheet, the flow shear across the boundary, and nonzero guide field. While effects of each of these elements have been studied, the effects arising from the combination of these are still unexplored. Two-dimensional full-particle simulations show that the combination of shear flow and/or guide field with density asymmetry induces the sliding motion of the X-line along the magnetopause. The direction of the X-line motion is controlled either by the ion flow at the X-line when the shear flow effects dominate or by the electron flow at the X-line when the guide field effects dominate. The shear flow effects and the guide field effects may counteract each other in determining the direction of the X-line motion and, in the close proximity of the subsolar region where the flow is slow, the X-line motion can be opposite to the flow direction

小胞体上の分泌タンパク質出芽部位ER exit siteの局在制御機構

学位の種別: 課程博士審査委員会委員 : （主査）東京大学教授 堅田 利明, 東京大学教授 一條 秀憲, 東京大学教授 富田 泰輔, 東京大学特任准教授 田口 友彦, 東京大学講師 前田 和哉University of Tokyo(東京大学

Chemical effect on muonic atom formation through muon transfer reaction in benzene and cyclohexane samples

To investigate the chemical effect on the muon capture process through a muon transfer reaction from a muonic hydrogen atom, the formation rate of muonic carbon atoms is measured for benzene and cyclohexane molecules in liquid samples. The muon transfer rate to carbon atoms of the benzene molecule is higher than that to the carbon atoms of the cyclohexane molecule. Such a deviation has never been observed among those molecules for gas samples. This may be because the transfers occur from the excited states of muonic hydrogen atoms in the liquid system, whereas in the gas system, all the transfers occur from the 1s (ground) state of muon hydrogen atoms. The muonic hydrogen atoms in the excited states have a larger radius than those in the 1s state and are therefore considered to be affected by the steric hindrance of the molecular structure. This indicates that the excited states of muonic hydrogen atoms contribute significantly to the chemical effects on the muon transfer reaction

Evaluation of Osteoconductive Scaffolds in the Canine Femoral Multi-Defect Model

Treatment of large segmental bone defects remains an unsolved clinical challenge, despite a wide array of existing bone graft materials. This project was designed to rapidly assess and compare promising biodegradable osteoconductive scaffolds for use in the systematic development of new bone regeneration methodologies that combine scaffolds, sources of osteogenic cells, and bioactive scaffold modifications. Promising biomaterials and scaffold fabrication methods were identified in laboratories at Rutgers, MIT, Integra Life Sciences, and Mayo Clinic. Scaffolds were fabricated from various materials, including poly(L-lactide-co-glycolide) (PLGA), poly(L-lactide-co-ɛ-caprolactone) (PLCL), tyrosine-derived polycarbonate (TyrPC), and poly(propylene fumarate) (PPF). Highly porous three-dimensional (3D) scaffolds were fabricated by 3D printing, laser stereolithography, or solvent casting followed by porogen leaching. The canine femoral multi-defect model was used to systematically compare scaffold performance and enable selection of the most promising substrate(s) on which to add cell sourcing options and bioactive surface modifications. Mineralized cancellous allograft (MCA) was used to provide a comparative reference to the current clinical standard for osteoconductive scaffolds. Percent bone volume within the defect was assessed 4 weeks after implantation using both MicroCT and limited histomorphometry. Bone formed at the periphery of all scaffolds with varying levels of radial ingrowth. MCA produced a rapid and advanced stage of bone formation and remodeling throughout the defect in 4 weeks, greatly exceeding the performance of all polymer scaffolds. Two scaffold constructs, TyrPC[subscript PL]/TCP and PPF4[subscript SLA]/HA[subscript PLGA Dip], proved to be significantly better than alternative PLGA and PLCL scaffolds, justifying further development. MCA remains the current standard for osteoconductive scaffolds.United States. Army Medical Research and Materiel Command (Armed Forces Institute of Regenerative Medicine)United States. Office of Naval ResearchUnited States. Air Force. Office of the Surgeon GeneralUnited States. NavyNational Institutes of Health (U.S.)United States. Veterans AdministrationCleveland Clinic Foundatio

Neuropeptide signaling through neurokinin-1 and neurokinin-2 receptors augments antigen presentation by human dendritic cells

Background: Neurotransmitters, including substance P (SP) and neurokinin A (NKA), are widely distributed in both the central and peripheral nervous system and their receptors, neurokinin-1 receptor (NK1R) and neurokinin-2 receptor (NK2R), are expressed on immune cells. However, the role of the NKA-NK2R axis in immune responses relative to the SP-NK1R signaling cascade has not been elucidated. Objective: We sought to examine the effect of neuropeptide signaling through NK1Rand NK2R on antigen presentation by dendritic cells (DCs) and the subsequent activation of effector Th cells. Methods: Expression levels of NK1R, NK2R, HLA-class II and costimulatory molecules of human MoDCs and cytokine production by birch pollen antigen-specific CD4+ T cells cocultured with MoDCs in the presence of NK1R and NK2R antagonists were evaluated by quantitative RT-PCR, flow cytometry or ELISA. NK1R and NK2R expression in the lung of patients with asthma and hypersensitivity pneumonitis was evaluated by immunohistochemistry. Results: Human MoDCs significantly upregulated NK2R and NK1R expression in response to poly I:C stimulation in a STAT1-dependent manner. Both NK2R and NK1R were expressed on alveolar macrophages and lung DCs from patients with asthma and pneumonitis hypersensitivity. Surface expression levels of HLA-class II and costimulatory molecules on DCs were modulated by NK1R or NK2R antagonists. Activation of birch pollen-derived antigen-specific CD4+ T cells and their production of cytokines including IL-4 and IFN-γ as well as IL-12 production by MoDCs, were suppressed by blocking NK1R or NK2R after in vitro antigen stimulation. Conclusions: NK1R- and NK2R-mediated neuropeptide signaling promotes both innate and acquired immune responses through activation of human DCs

Interaction Rating Scale (IRS) as an Evidence-Based Practical Index of Children’s Social Skills and Parenting

Background: The purpose of this paper is to describe the features of the Interaction Rating Scale (IRS) as an evidence-based practical index of children’s social skills and parenting.Methods: The participants in our study, which was conducted as part of a Japan Science and Technology Agency (JST) project, were 370 dyads of children (aged 18, 30, and 42 month) and 81 dyads of 7-year-old children with their caregivers. The participants completed the five minute interaction session and were observed using the IRS.Results: The results indicated that the IRS can measure children’s social skill development and parenting with high validity. Along with the discriminate validity for pervasive development disorder (PDD), attention-deficit/hyperactivity disorder (ADHD), abuse and maltreatment, a high correlation with the SDQ (Strength and Difficulties Questionnaire), and high reliability, the IRS is effective in describing features of social skill development.Conclusions: The IRS provides further evidence of the fact that in order to study children’s social skill development, it is important to evaluate various features of the caregiver-child interaction as a predictor of social skills