Sh3bp2 Gain-Of-Function Mutation Ameliorates Lupus Phenotypes in B6.MRL-Faslpr Mice

SH3 domain-binding protein 2 (SH3BP2) is an adaptor protein that is predominantly expressed in immune cells, and it regulates intracellular signaling. We had previously reported that a gain-of-function mutation in SH3BP2 exacerbates inflammation and bone loss in murine arthritis models. Here, we explored the involvement of SH3BP2 in a lupus model. Sh3bp2 gain-of-function (P416R knock-in; Sh3bp2KI/+) mice and lupus-prone B6.MRL-Faslpr mice were crossed to yield double-mutant (Sh3bp2KI/+Faslpr/lpr) mice. We monitored survival rates and proteinuria up to 48 weeks of age and assessed renal damage and serum anti-double-stranded DNA antibody levels. Additionally, we analyzed B and T cell subsets in lymphoid tissues by flow cytometry and determined the expression of apoptosis-related molecules in lymph nodes. Sh3bp2 gain-of-function mutation alleviated the poor survival rate, proteinuria, and glomerulosclerosis and significantly reduced serum anti-dsDNA antibody levels in Sh3bp2KI/+Faslpr/lpr mice. Additionally, B220+CD4-CD8- T cell population in lymph nodes was decreased in Sh3bp2KI/+Faslpr/lpr mice, which is possibly associated with the observed increase in cleaved caspase-3 and tumor necrosis factor levels. Sh3bp2 gain-of-function mutation ameliorated clinical and immunological phenotypes in lupus-prone mice. Our findings offer better insight into the unique immunopathological roles of SH3BP2 in autoimmune diseases

SH3BP2 Deficiency Ameliorates Murine Systemic Lupus Erythematosus

Background: The adaptor protein Src homology 3 domain-binding protein 2 (SH3BP2) is widely expressed in immune cells. It controls intracellular signaling pathways. The present study was undertaken to investigate the role of SH3BP2 in a murine systemic lupus erythematosus model. Methods: For the lupus model, we used Faslpr/lpr mice. Clinical and immunological phenotypes were compared between Faslpr/lpr and SH3BP2-deficient Faslpr/lpr mice. Splenomegaly and renal involvement were assessed. Lymphocyte subsets in the spleen were analyzed by flow cytometry. To examine the role of SH3BP2 in specific cells, B cell-specific SH3BP2-deficient lupus mice were analyzed; T cells and bone marrow-derived dendritic cells and macrophages were analyzed in vitro. Results: SH3BP2 deficiency significantly reduced lupus-like phenotypes, presented as splenomegaly, renal involvement, elevated serum anti-dsDNA antibody, and increased splenic B220+CD4−CD8− T cells. Notably, SH3BP2 deficiency in B cells did not rescue the lupus-like phenotypes. Furthermore, SH3BP2 deficiency did not substantially affect the characteristics of T cells and macrophages in vitro. Interestingly, SH3BP2 deficiency suppressed the differentiation of dendritic cells in vitro and reduced the number of dendritic cells in the spleen of the lupus-prone mice. Conclusions: SH3BP2 deficiency ameliorated lupus-like manifestations. Modulating SH3BP2 expression could thus provide a novel therapeutic approach to autoimmune diseases

リチウム鉛流れの高温超音波ドップラー流速計測法の構築

京都大学0048新制・課程博士博士(工学)甲第17159号工博第3649号新制||工||1554(附属図書館)29898京都大学大学院工学研究科原子核工学専攻(主査）教授 功刀 資彰, 教授 福山 淳, 准教授 横峯 健彦学位規則第4条第1項該当Doctor of Philosophy (Engineering)Kyoto UniversityDA

Proof of concept of acoustic detection of boiling inception and state transition using deep neural network

We develop a deep neural network model capable of detecting the boiling inception and state transitions from boiling acoustic measurements. We characterize acoustic spectrums of water boiling with different heating surface geometries, heat flux, and degree of subcooling. Our measurement result shows that the feature extraction of the boiling inception and state transition is possible from the boiling-sound frequency dataset in each specific target system. Notably, the deep neural network can distinguish the boiling inception and the state transition more accurately even at the high-level white-noise intensity where human beings and traditional data analysis methods cannot distinguish. This result suggests that the acoustic diagnosis with the deep neural network algorithm has great potential to detect the boiling inception and to monitor the boiling states in quasi-real-time during an early stage of the boiling phenomena, in the nuclear power plants

Molecular dynamics study of instantaneous interfacial thermal resistance of droplets on flat crystalline surface during cooling and ice formation

Condensation and frost formation degrade the heat transfer performance of air-conditioners and refrigerators. Yet, the frost formation mechanism has not been fully understood. In the present study, we numerically investigate nanoscale H2O droplets during cooling and ice formation utilizing classical molecular dynamics simulations. The mW potential is employed for the H2O molecules. A nanoscale H2O droplet is placed on a flat solid wall consisting of Pt or Pb atoms. We examine where ice nucleation is formed and how the ice formation proceeds inside the droplet, and then evaluate the time change in instantaneous interfacial thermal resistance between the H2O molecules and the solid wall. In common with Pt and Pb surfaces, the time changes in the instantaneous interfacial thermal resistance and the density depletion length are qualitatively consistent in the present transient thermal energy transfer process together with the phase change. In addition, the relation of the time-averaged instantaneous interfacial thermal resistance and the density depletion length are qualitatively consistent with the relation of the solid-liquid interfacial thermal resistance in the steady-state

Contact angle measurement of molten lead–lithium on silicon carbide surfaces

Measurements of the contact angles at the different temperatures of a molten lead–lithium eutectic alloy (PbLi) droplet on a silicon carbide (SiC) wall are needed for the research and development both of a magnetic confinement fusion (MCF) and an inertia confinement fusion (ICF) blankets. PbLi coolant/breeder flows in the coolant channel, which is made of the SiC walls, and will experience a flow slip at the wall, called as a magnetohydrodynamic (MHD) slip flow. The ICF blanket adopts a molten PbLi film flow along the first wall made of SiC. The PbLi contact angle database is necessary as the thermal property for numerically predicting the behavior of the flowing molten PbLi film. This study attempts the measurement of the contact angles between the molten PbLi and the various SiC surfaces. For example, in order to examine the initial PbLi wettability, we measured the contact angles of a chemical vapor deposition (CVD) SiC, a nano-infiltration and transient eutectic-phase (NITE) SiC/SiC composites, and a NITE SiC in an inert atmosphere. We obtained the contact angle database of the molten PbLi, varying the temperature of PbLi from 250 to 400 °C, on a surface-polished as well as an unpolished SiC