Space-Time法による心臓弁の接触を含む高精度流体解析

早大学位記番号:新8436早稲田大

Molecular Mechanisms Behind the Chemopreventive Effects of Anthocyanidins

Anthocyanins are polyphenolic ring-based flavonoids, and are widespread in fruits and vegetables of red-blue color. Epidemiological investigations and animal experiments have indicated that anthocyanins may contribute to cancer chemoprevention. The studies on the mechanism have been done recently at molecular level. This review summarizes current molecular bases for anthocyanidins on several key steps involved in cancer chemoprevention: (i) inhibition of anthocyanidins in cell transformation through targeting mitogen-activated protein kinase (MAPK) pathway and activator protein 1 (AP-1) factor; (ii) suppression of anthocyanidins in inflammation and carcinogenesis through targeting nuclear factor kappa B (NF-κB) pathway and cyclooxygenase 2 (COX-2) gene; (iii) apoptotic induction of cancer cells by anthocyanidins through reactive oxygen species (ROS) / c-Jun NH(2)-terminal kinase (JNK)-mediated caspase activation. These data provide a first molecular view of anthocyanidins contributing to cancer chemoprevention

Characterization of Acylated Anthocyanins in Callus Induced From Storage Root of Purple-Fleshed Sweet Potato, Ipomoea batatas L

Four anthocyanins were isolated from a highly pigmented callus induced from the storage root of purple-fleshed sweet potato (Ipomoea batatas L) cultivar Ayamurasaki. The anthocyanins were respectively identified as cyanidin 3-O-(2-O-(6-O-(E)-caffeoyl-β-D-glucopyranosyl)-β-D-glucopyranoside) -5-O-β-D-glucopyranoside, cyanidin 3-O-(2-O-(6-O-(E)-p -coumaroyl-β-D-glucopyranosyl)-6-O-(E)-caffeoyl-β-D-glucopyranoside)-5-O-β-D-glucopyranoside, cyanidin 3-O-(2-O-(6-O-(E)-p -coumaroyl-β-D-glucopyranosyl)-6-O-(E)-p-coumaroyl-β-D-glucopyranoside)- 5-O-β-D-glucopyranoside, and peonidin 3-O-(2-O-(6-O-(E)-p -coumaroyl-β-D-glucopyranosyl)-6-O-(E)-p-coumaroyl-β-D-glucopyranoside)-5-O-β-D-glucopyranoside by chemical and spectroscopic analyses. These anthocyanins were examined with respect to the stability in neutral aqueous solution as well as the radical scavenging activity against the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical. These acylated anthocyanins exhibited both higher stability and higher DPPH radical scavenging activity than corresponding nonacylated cyanidin and peonidin 3-O-sophoroside-5-O-glucosides

ISOLATION AND CHARACTERIZATION OF A NOVEL HYALURONIDASE INHIBITOR FROM A MARINE ACTINOMYCETES STRAIN

A novel hyaluronidase inhibitor (HI) was isolated from the culture extract of a marine- derived actinomycete strain. This strain MB-PO13 was isolated from ascidian (Molgula manhattensis) in Tokyo Bay. Out of about 1,000 isolates from various marine organisms, strain MB-PO13 had the strongest inhibitory activity and was selected for further study. The strain showed abundant-to-moderate growth on most media, forming a grayish mycelium. On the basis of the taxonomical characteristics, the strain was classified as belonging to the genus of Streptomyces and was named as Streptomyces sp. strain MB-PO13. The structure of HI was elucidated by interpretation of NMR data. HI displayed about 25-fold potent hyaluronidase inhibitory activity against hyaluronidase than glycyrrhizin. Keywords: marine actinomycetes; Streptomyces; hyaluronidase inhibitor

Heart valve isogeometric sequentially-coupled FSI analysis with the space–time topology change method

Heart valve fluid–structure interaction (FSI) analysis is one of the computationally challenging cases in cardiovascular fluid mechanics. The challenges include unsteady flow through a complex geometry, solid surfaces with large motion, and contact between the valve leaflets. We introduce here an isogeometric sequentially-coupled FSI (SCFSI) method that can address the challenges with an outcome of high-fidelity flow solutions. The SCFSI analysis enables dealing with the fluid and structure parts individually at different steps of the solutions sequence, and also enables using different methods or different mesh resolution levels at different steps. In the isogeometric SCFSI analysis here, the first step is a previously computed (fully) coupled Immersogeometric Analysis FSI of the heart valve with a reasonable flow solution. With the valve leaflet and arterial surface motion coming from that, we perform a new, higher-fidelity fluid mechanics computation with the space–time topology change method and isogeometric discretization. Both the immersogeometric and space–time methods are variational multiscale methods. The computation presented for a bioprosthetic heart valve demonstrates the power of the method introduced

Identification of Novel Genes Selectively Expressed in the Follicle-Associated Epithelium from the Meta-Analysis of Transcriptomics Data from Multiple Mouse Cell and Tissue Populations

The follicle-associated epithelium (FAE) overlying the Peyer’s patches and the microfold cells (M cells) within it are important sites of antigen transcytosis across the intestinal epithelium. Using a meta-analysis approach, we identified a transcriptional signature that distinguished the FAE from a large collection of mouse cells and tissues. A co-expressed cluster of 21 FAE-specific genes was identified, and the analysis of the transcription factor binding site motifs in their promoter regions indicated that these genes shared an underlying transcriptional programme. This cluster contained known FAE- (Anxa10, Ccl20, Psg18 and Ubd) and M-cell-specific (Gp2) genes, suggesting that the others were novel FAE-specific genes. Some of these novel candidate genes were expressed highly by the FAE and M cells (Calcb, Ces3b, Clca2 and Gjb2), and others only by the FAE (Ascl2, Cftr, Fgf15, Gpr133, Kcna1, Kcnj15,Mycl1, Pgap1 and Rps6kl). We also identified a subset of novel FAE-related genes that were induced in the intestinal epithelium after receptor activatorof nuclear factor (NF)-kB ligand stimulation. These includedMfge8whichwas specific to FAE enter-ocytes. This studyprovides new insight into the FAE transcriptome. Furthercharacterizationof the candidate genes identified here will aid the identification of novel regulators of cell function in the FAE

気相中におけるMg+(NH3)nの溶媒和構造

2004年分子構造総合討論会, 2004年9月27日-30日, 広島国際会議場(広島), 2P03

CD4+ T Responses Other Than Th1 Type Are Preferentially Induced by Latency-Associated Antigens in the State of Latent Mycobacterium tuberculosis Infection.

Mycobacterium tuberculosis (M. tuberculosis) produces a diverse range of antigenic proteins in its dormant phase. The cytokine profiles of CD4+ T cell responses, especially subsets other than Th1 type (non-Th1 type), against these latency-associated M. tuberculosis antigens such as α-crystallin (Acr), heparin-binding hemagglutinin (HBHA), and mycobacterial DNA-binding protein 1 (MDP-1) remain elusive in relation to the clinical stage of M. tuberculosis infection. In the present study, peripheral blood mononuclear cells (PBMCs) collected from different stages of M. tuberculosis-infected cases and control PBMCs were stimulated with these antigens and ESAT-6/CFP-10. Cytokine profiles of CD4+ T cells were evaluated by intracellular cytokine staining using multicolor flow cytometry. Our results demonstrate that Th1 cytokine responses were predominant after TB onset independent of the type of antigen stimulation. On the contrary, non-Th1 cytokine responses were preferentially induced by latency-associated M. tuberculosis antigens, specifically IL-10 response against Acr in latent M. tuberculosis infection. From these results, we surmise a shift in the CD4+ T cell response from mixed non-Th1 to Th1 dominant type during TB progression

A novel M cell–specific carbohydrate-targeted mucosal vaccine effectively induces antigen-specific immune responses

Mucosally ingested and inhaled antigens are taken up by membranous or microfold cells (M cells) in the follicle-associated epithelium of Peyer's patches or nasopharynx-associated lymphoid tissue. We established a novel M cell–specific monoclonal antibody (mAb NKM 16–2-4) as a carrier for M cell–targeted mucosal vaccine. mAb NKM 16–2-4 also reacted with the recently discovered villous M cells, but not with epithelial cells or goblet cells. Oral administration of tetanus toxoid (TT)– or botulinum toxoid (BT)–conjugated NKM 16–2-4, together with the mucosal adjuvant cholera toxin, induced high-level, antigen-specific serum immunoglobulin (Ig) G and mucosal IgA responses. In addition, an oral vaccine formulation of BT-conjugated NKM 16–2-4 induced protective immunity against lethal challenge with botulinum toxin. An epitope analysis of NKM 16–2-4 revealed specificity to an α(1,2)-fucose–containing carbohydrate moiety, and reactivity was enhanced under sialic acid–lacking conditions. This suggests that NKM 16–2-4 distinguishes α(1,2)-fucosylated M cells from goblet cells containing abundant sialic acids neighboring the α(1,2) fucose moiety and from non-α(1,2)-fucosylated epithelial cells. The use of NKM 16–2-4 to target vaccine antigens to the M cell–specific carbohydrate moiety is a new strategy for developing highly effective mucosal vaccines

A humanized mouse model identifies key amino acids for low immunogenicity of H7N9 vaccines

Influenza vaccines of H7N9 subtype are consistently less immunogenic in humans than vaccines developed for other subtypes. Although prior immunoinformatic analysis identified T-cell epitopes in H7 hemagglutinin (HA) which potentially enhance regulatory T cell response due to conservation with the human genome, the links between the T-cell epitopes and low immunogenicity of H7 HA remains unknown due to the lack of animal models reproducing the response observed in humans. Here, we utilized a humanized mouse model to recapitulate the low immunogenicity of H7 HA. Our analysis demonstrated that modification of a single H7 epitope by changing 3 amino acids so that it is homologous with a known H3 immunogenic epitope sequence significantly improved the immunogenicity of the H7 HA in the humanized mouse model, leading to a greater than 4-fold increase in HA-binding IgG responses. Thus, we provide experimental evidence for the important contribution of this H7-specific T cell epitope in determining the immunogenicity of an influenza vaccine. Furthermore, this study delineates strategies that can be used for screening and selecting vaccine strains using immunoinformatics tools and a humanized mouse model