Involvement of GANP in B Cell Activation in T Cell-dependent Antigen Response

Adaptive immunity is dependent on proliferation of antigen-driven B cells for clonal expansion in germinal centers (GCs) against T cell-dependent antigens (TD-Ag), accompanied with somatic hypermutation of variable-region gene and class switching of B cell antigen receptors. To study molecular mechanisms for B cell differentiation in GCs, we have identified and studied a 210 kDa GANP protein expressed in GC-B cells. GANP has domains for MCM3-binding and RNA-primase activities and is selectively up-regulated in centrocytes surrounded with follicular dendritic cells (FDCs) upon immunization with TD-Ag in vivo and in B cells stimulated with anti-CD40 monoclonal antibody in vitro, which suggested that GANP plays a certain important role in the maturation of immunoglobulin or selection of B cells in GC during the immune response to TD-Ag. Since this up-regulation has not been detected in T cells in GCs and in Concanavalin A-stimulated T cells in vitro, selective function of GANP molecule on B cell proliferation and differentiation might exist

Hierarchy Builder: algebraic hierarchies made easy in Coq with Elpi

International audienceIt is nowadays customary to organize libraries of machine checked proofs around hierarchies of algebraic structures [2, 6, 8, 16, 18, 23, 27]. One influential example is the Mathematical Components library on top of which the long and intricate proof of the Odd Order Theorem could be fully formalized [14]. Still, building algebraic hierarchies in a proof assistant such as Coq [9] requires a lot of manual labor and often a deep expertise in the internals of the prover [13, 17]. Moreover, according to our experience [26], making a hierarchy evolve without causing breakage in client code is equally tricky: even a simple refactoring such as splitting a structure into two simpler ones is hard to get right. In this paper we describe HB, a high level language to build hierarchies of algebraic structures and to make these hierarchies evolve without breaking user code. The key concepts are the ones of factory, builder and abbreviation that let the hierarchy developer describe an actual interface for their library. Behind that interface the developer can provide appropriate code to ensure retro compatibility. We implement the HB language in the hierarchy-builder addon for the Coq system using the Elpi [11, 28] extension language

Strategies to enhance the excitation energy-transfer efficiency in a light-harvesting system using the intra-molecular charge transfer character of carotenoids

Fucoxanthin is a carotenoid that is mainly found in light-harvesting complexes from brown algae and diatoms. Due to the presence of a carbonyl group attached to polyene chains in polar environments, excitation produces an excited intra-molecular charge transfer. This intra-molecular charge transfer state plays a key role in the highly efficient (∼95%) energy-transfer from fucoxanthin to chlorophyll a in the light-harvesting complexes from brown algae. In purple bacterial light-harvesting systems the efficiency of excitation energy-transfer from carotenoids to bacteriochlorophylls depends on the extent of conjugation of the carotenoids. In this study we were successful, for the first time, in incorporating fucoxanthin into a light-harvesting complex 1 from the purple photosynthetic bacterium, Rhodospirillum rubrum G9+ (a carotenoidless strain). Femtosecond pump-probe spectroscopy was applied to this reconstituted light-harvesting complex in order to determine the efficiency of excitation energy-transfer from fucoxanthin to bacteriochlorophyll a when they are bound to the light-harvesting 1 apo-proteins

Holes in the valence band of superconducting boron-doped diamond film studied by soft X-ray absorption and emission spectroscopy

Carbon- and boron-2$p$ states of superconducting and non-superconducting boron-doped diamond samples are measured using soft X-ray emission and absorption spectroscopy. For the superconducting sample, a large density of hole states is observed in the valence band in addition to the states in the impurity band. The hole states in the valence band is located at about 1.3 eV below the valence band maximum regardless of the doping level, which cannot be interpreted within a simple rigid band model. Present experimental results, combined with the first principles calculations, suggest that superconductivity is to be attributed to the holes in the valence band.Comment: 4 pages, 4 figure

Preclinical Safety and Efficacy of in Situ REIC/Dkk-3 Gene Therapy for Prostate Cancer

The preclinical safety and therapeutic efficacy of adenoviral vectors that express the REIC/Dkk-3 tumor suppressor gene (Ad-REIC) was examined for use in prostate cancer gene therapy. The Ad-human (h) and mouse (m) REIC were previously demonstrated to induce strong anti-cancer effects in vitro and in vivo, and we herein report the results of two in vivo studies. First, intra-tumor Ad-hREIC administration was examined for toxicity and therapeutic effects in a subcutaneous tumor model using the PC3 prostate cancer cell line. Second, intra-prostatic Ad-mREIC administration was tested for toxicity in normal mice. The whole-body and spleen weights, hematological and serum chemistry parameters, and histological evaluation of tissues from throughout the body were analyzed. Both experiments indicated that there was no significant difference in the examined parameters between the Ad-REIC-treated group and the control (PBS- or Ad-LacZ-treated) group. In the in vitro analysis using PC3 cells, a significant apoptotic effect was observed after Ad-hREIC treatment. Confirming this observation, the robust anti-tumor efficacy of Ad-hREIC was demonstrated in the in vivo subcutaneous prostate cancer model. Based on the results of these preclinical experiments, we consider the adenovirus-mediated REIC/Dkk-3 in situ gene therapy to be safe and useful for the clinical treatment of prostate cancer

Dkk3/REIC Deficiency Impairs Spermiation, Sperm Fibrous Sheath Integrity and the Sperm Motility of Mice

The role of Dickkopf-3 (Dkk3)/REIC (The Reduced Expression in Immortalized Cells), a Wnt-signaling inhibitor, in male reproductive physiology remains unknown thus far. To explore the functional details of Dkk3/REIC in the male reproductive process, we studied the Dkk3/REIC knock-out (KO) mouse model. By examining testicular sections and investigating the sperm characteristics (count, vitality and motility) and ultrastructure, we compared the reproductive features between Dkk3/REIC-KO and wild-type (WT) male mice. To further explore the underlying molecular mechanism, we performed RNA sequencing (RNA-seq) analysis of testicular tissues. Our results showed that spermiation failure existed in seminiferous tubules of Dkk3/REIC-KO mice, and sperm from Dkk3/REIC-KO mice exhibited inferior motility (44.09 +/- 8.12% vs. 23.26 +/- 10.02%, p 0.05) nor the difference in the sperm vitality rate (72.83 +/- 1.55% vs. 72.50 +/- 0.71%, p > 0.05) were statistically significant. The RNA-seq and GO (Gene Oncology) enrichment results indicated that the differential genes were significantly enriched in the GO terms of cytoskeleton function, cAMP signaling and calcium ion binding. Collectively, our research demonstrates that Dkk3/REIC is involved in the process of spermiation, fibrous sheath integrity maintenance and sperm motility of mice

Preclinical Evaluation of MicroRNA-34b/c Delivery for Malignant Pleural Mesothelioma

The microRNA-34s (miR-34s) have p53 response elements in their 5ʼ-flanking regions and demonstrate tumor-suppressive functions. In malignant pleural mesothelioma (MPM), we previously reported that expression of miR-34b and miR-34c (miR-34b/c) was frequently downregulated by methylation in MPM cell lines and primary tumors. The forced overexpression of miR-34b/c showed significant antitumor effects with the induction of apoptosis in MPM cells. In this study, we examined the in vivo antitumor effects of miR-34b/c using adenovirus vector on MPM. We subcutaneously transplanted NCI-H290, a human MPM cell line, into BALB/C mice and injected adenovirus vector expressing miR-34b/c, luciferase driven by the cytomegalovirus promoter (Ad-miR-34b/c or Ad-Luc), or PBS control into tumors over 5mm in diameter. A statistically significant growth inhibition of the tumor volume was observed in the Ad-miR-34b/c group from day 6 onward compared to the Ad-Luc group. The inhibition rate of Ad-miR-34b/c, compared to the tumor volume treated with Ad-Luc, was 58.6% on day 10 and 54.7% on day13. Our results indicate that adenovirus-mediated miR-34b/c gene therapy could be useful for the clinical treatment of MPM

<Original>ESCA Study on Improvements in Adhesive Ability of Dental Adhesive Resin to Ni-Cr Alloy Treated by HNO_3 Solution

Ni-Cr合金を濃硝酸で処理すると研磨したままの場合よりも接着性レジン(4-META/MMA-TBB)に対する接着性が著しく向上する。その理由を解明するために硝酸処理と研磨したままの合金表面をX線光電子分光分析装置(ESCA)で分析し, 両者の表面構造を解析した。研磨したままでの合金表面におけるNiとCrの濃度は, Ni 21at%, Cr 17%であるが, 硝酸処理を施すとNi 13%, Cr 25%になった。硝酸処理によって合金表面で, 4-META レジンに対する親和性の劣るNiが減少し, 親和性の優れたCrが増加した。また, O 1sスペクトルを解析すると, 次の3つの酸素に由来する成分に分解された。成分Iは不動態被膜のCr-O-Crに由来する酸素, IIは不動態被膜中のCr-OH・・・H_2Oに由来する酸素, IIIは被膜上に存在する吸着水に由来する酸素である。これらの成分の存在比は, 研磨したままでは, II>I>IIIの順であるが, 硝酸処理では, 1>II>IIIになった。これらは, 硝酸処理によって, 4 -META レジンに対する接着性が優れている不動態被膜が強固に形成していることを示す。The adhesive ability of dental adhesive resin (4-META/MMA-TBB) to Ni-Cr alloy improves remarkably when the alloy surface is treated by cone. HNO_3 solution. Both as -polished and cone. HNO_3 treated alloy surfaces were analyzed by Electron Spectroscopy for Chemical Analysis (ESCA) to explain the superior adhesive ability of the alloy surface treated with HNO_3. The surface of the HNO_3 treated specimen contains 25 at % Cr and 13% Ni and the as -polished specimen contains 17% Cr and 21% Ni. It shows that Cr, which has a good chemical affinjty for 4-META resin, is concentrated on the alloy surface. The Q lg spectra can be separated into three components: Component I is due to oxygen bonded with chromium in the passive film, Cr-OCr; II is due to oxygen bonded with both chromium and hydrogen in the passive film, Cr-OH ・ ・ ・ OH_2; and III is due to oxygen in physisorbed water molecules on the passive film. The area fractions are in the order II>I>III for the as-polished surface and I>II>III for the HNO_3 treated surface, indicating that a firm passive structure is formed on the surface treated by HNO_3 solution. This is the cause of the increase in the adhesive ability of the 4-META resin on the passive film

Design and Demonstration of a Neutron Spin Flipper for a New Neutron Reflectometer SHARAKU at J-PARC

AbstractA new neutron reflectometer SHARAKU with vertical sample-plane geometry was installed on the beam line 17 (BL17) at Materials and Life science experiment Facility (MLF) at J-PARC. Magnetism in a thin magnetic film is one of the main targets on SHARAKU and polarizing devices and neutron spin flippers are required. Since polarized neutrons of wavelength from 0.24nm to 0.64nm can be used on SHARAKU, a neutron spin flipper has to control white neutron beam. A two-coil neutron spin flipper (Drabkin spin flipper) is one of the powerful devices to control neutron spin with white beam. In this study, the two-coil flipper was designed and installed in SHARAKU. Demonstration of the two-coil flipper was also performed and polarization of more than 0.95 with wavelengths ranging from 0.24nm to 0.64nm was obtained