Serum Amyloid A3 Promoter-Driven Luciferase Activity Enables Visualization of Diabetic Kidney Disease

The early detection of diabetic nephropathy (DN) in mice is necessary for the development of drugs and functional foods. The purpose of this study was to identify genes that are significantly upregulated in the early stage of DN progression and develop a novel model to non-invasively monitor disease progression within living animals using in vivo imaging technology. Streptozotocin (STZ) treatment has been widely used as a DN model; however, it also exhibits direct cytotoxicity to the kidneys. As it is important to distinguish between DN-related and STZ-induced nephropathy, in this study, we compared renal responses induced by the diabetic milieu with two types of STZ models: multiple low-dose STZ injections with a high-fat diet and two moderate-dose STZ injections to induce DN. We found 221 genes whose expression was significantly altered during DN development in both models and identified serum amyloid A3 (Saa3) as a candidate gene. Next, we applied the Saa3 promoter-driven luciferase reporter (Saa3-promoter luc mice) to these two STZ models and performed in vivo bioluminescent imaging to monitor the progression of renal pathology. In this study, to further exclude the possibility that the in vivo bioluminescence signal is related to renal cytotoxicity by STZ treatment, we injected insulin into Saa3-promoter luc mice and showed that insulin treatment could downregulate renal inflammatory responses with a decreased signal intensity of in vivo bioluminescence imaging. These results strongly suggest that Saa3 promoter activity is a potent non-invasive indicator that can be used to monitor DN progression and explore therapeutic agents and functional foods.     

Mechano-electrochemistry of a passive surface using an in situ micro-indentation test

Depassivation–repassivation of iron surfaces in boric–borate solutions were investigated by using the micro-indentation test. A pair of current peaks due to repair of the passive film following rupture of the film were observed during a series of indenter drives, i.e., loading and unloading of the indenter. The shape of the current peak depended on environmental conditions (conductivity and pH of the solution) and substrate conditions (mechanical processing history, alloyed element) as well as indentation conditions (repetition, maximum depth, and maximum load). Plastic deformation of the surface was accompanied by surface depassivation, while no depassivation occurred during the elastic deformation, indicating that the passive film on iron has a ductile property. The solution conditions did not affect the scale of depassivation but affected the rate of repassivation. Dislocations in the substrate made surface depassivation difficult but enhanced reactivity during the repassivation. The test also revealed that type-312L stainless steel has high corrosion resistance in a concentrated NaCl solution.     

What is the significance of nitrogen-vacancy centers in the doping into diamond?

In order to advance quantum computer after successful synthesis of a qubit (quantum-bit) using a NV (nitrogen-vacancy) center in diamond crystal, the innovation of a NOT processor is strongly demanded. A candidate of it can be one NV center associated with an additional N atom, which is called a NV–N center. Making use of a classical molecular dynamics simulation of N ion implantation into pure diamond with an energy of 200 eV, we have examined the crystallographic structure of “NV–N” centers. However, at low temperature of 30 K, most implanted N atoms became interstitials, thus it was difficult to identify even NV centers.     

Quantitative Visualization of the Interaction between Complement Component C1 and Immunoglobulin G: The Effect of CH1 Domain Deletion

Immunoglobulin G (IgG) adopts a modular multidomain structure that mediates antigen recognition and effector functions, such as complement-dependent cytotoxicity. IgG molecules are self-assembled into a hexameric ring on antigen-containing membranes, recruiting the complement component C1q. In order to provide deeper insights into the initial step of the complement pathway, we report a high-speed atomic force microscopy study for the quantitative visualization of the interaction between mouse IgG and the C1 complex composed of C1q, C1r, and C1s. The results showed that the C1q in the C1 complex is restricted regarding internal motion, and that it has a stronger binding affinity for on-membrane IgG2b assemblages than C1q alone, presumably because of the lower conformational entropy loss upon binding. Furthermore, we visualized a 1:1 stoichiometric interaction between C1/C1q and an IgG2a variant that lacks the entire C_H1 domain in the absence of an antigen. In addition to the canonical C1q-binding site on Fc, their interactions are mediated through a secondary site on the C_L domain that is cryptic in the presence of the C_H1 domain. Our findings offer clues for novel-modality therapeutic antibodies.     

Monte Carlo uncertainty quantification of the effective delayed neutron fraction

The applicability of Monte Carlo techniques, namely the Monte Carlo sensitivity method and the random-sampling method, for uncertainty quantification of the effective delayed neutron fraction β_eff is investigated using the continuous-energy Monte Carlo transport code, MCNP, from the perspective of statistical convergence issues. This study focuses on the nuclear data as one of the major sources of β_eff uncertainty. For validation of the calculated β_eff, a critical configuration of the VENUS-F zero-power reactor was used. It is demonstrated that Chiba's modified k-ratio method is superior to Bretscher's prompt k-ratio method in terms of reducing the statistical uncertainty in calculating not only β_eff but also its sensitivities and the uncertainty due to nuclear data. From this result and a comparison of uncertainties obtained by the Monte Carlo sensitivity method and the random-sampling method, it is shown that the Monte Carlo sensitivity method using Chiba's modified k-ratio method is the most practical for uncertainty quantification of β_eff. Finally, total β_eff uncertainty due to nuclear data for the VENUS-F critical configuration is determined to be approximately 2.7% with JENDL-4.0u, which is dominated by the delayed neutron yield of ²³⁵U.     

Performance Evaluation of Magnetostrictive Small Wind Turbines Using Fe–Co Alloy–Based Clad Sheets

In this study, the Fe–Co alloy is combined with cobalt ferrite (CoFe₂O₄) and nickel (Ni) to form Fe–Co/CoFe₂O₄ and Fe–Co/Ni clad sheets and their energy-harvesting performance is evaluated. The Fe–Co/CoFe₂O₄ clad sheet exhibits an output voltage of 4.229 mV and an output power of 6.89 nW at a wind speed of 10 m s⁻¹. The energy-harvesting performance of both these clad sheets cannot be quantitatively compared owing to their different thicknesses, which result in varying volume and distance from the neutral plane. Nevertheless, the values of output voltage and power for Fe–Co/CoFe₂O₄ are higher than those for Fe–Co/Ni (2.107 mV and 0.294 nW).     

Study on the "signal" constituents for the evaluation of animal crude drugs. V. The "signal" constituents for the identification of Lumbricus in cold medicines

Cell death was analyzed in neurulating mouse embryos after in vivo doses of 2-methoxyethanol (2-ME) that produce anterior neural tube defects. Characterization of 2-ME-induced cell death was performed by evaluating: (1) vital fluorochrome staining in whole embryos applying confocal laser scanning microscopy; (2) characteristics of cell debris in conventional histological sections revealed by light microscopy; and (3) Apoptag in situ immunohistochemical staining for apoptosis using light microscopy. Methods for quantification of cell death identified by these three techniques were explored using computerized image analysis. Physiological cell death in control embryos primarily occurred in the neural crest region during neural fold elevation. Embryos exposed to 2-ME had expanded areas of cell death in the neural crest and also new areas of cell death in medial regions of the anterior neural tube. Both physiological and 2-ME-induced embryonic cell death had morphological, immunohistochemical, and fluorochrome staining characteristics of apoptosis. When fluorescence data from confocal microscopic analysis of vital fluorochrome-stained embryos were analyzed, a dose-dependent increase was found in embryos exposed to 2-ME. Similar results were obtained when cell death was analyzed in either conventional histological sections or sections prepared for immunohistochemical detection of apoptosis. The cell death data obtained in this study correlate with previously observed near-term malformation rates, suggesting that a quantitative relationship exists between 2-ME-induced embryonic cell death and neural tube defects.     

Ossifying epithelioid hemangioendothelioma

A case of small epithelioid hemangioendothelioma encapsulated by an egg-shaped bony shell composed of newly formed mature lamellar bone is presented. A nodule measuring 10 x 5 x 5 mm was excised from inside of the right cheek muscle of a 46-year-old man. Histopathologically, the nodule consisted mainly of round-to-short spindled epithelioid cells with round nuclei and occasional cytoplasmic vacuoles associated with some foci of osseous metaplasia. Characteristically, egg shell-like lamellar bone enclosed this lesion showing well-circumscribed appearance. The main component cells were immunohistochemically stained positive for factor VIII-related antigen, CD 34, UEA-1, and vimentin, and proved to be vascular endothelial cells. The term ossifying epithelioid hemangioendothelioma is proposed for this unique lesion. This type of epithelioid hemangioendothelioma has not been previously reported to our knowledge, and differentiation from ossifying fibromyxoid tumor of soft parts is considered to be important.