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Coarse-grained simulations of branched bilayer membranes: effects of cholesterol-dependent phase separation on curvature-driven lipid sorting

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Journal of Biophysical Chemistry 2011年第3期2卷 268-284页

作者： manami nishizawa Kazuhisa nishizawa Department of Laboratory Medicine Teikyo University School of Medical Technology Tokyo Japan

Our recent coarse-grained (CG) molecular dynamics (MD) simulations of membranes with a hemifused-ribbon (λ-shaped) geometry showed curvature-driven demixing leading to enrich ment in dioleoyl-phosphatidylethanolamine (DOPE) in a negatively-curved region (at C = –0.8 nm–1) of a DOPE/dipalmitoyl-phosphati-dylcholine (DPPC) membrane. Here we extend the analysis with respect to lipid composition and simulation time. Simulations of 12 – 20 μs effective time show that, compared with DOPE of the DOPE/DPPC system, a DPPC/dilinoleyl-PC [di(18:2)PC] membrane showed a similar degree of enrichment of di(18:2)PC in the curved region with C=–0.8 nm–1. For the latter mixture, even weak negative curvatures (C=–0.5 – 0.6 nm–1) caused significant degrees of di(18:2)PC enrichment. In agreement with recent studies of a planar bilayer, a ternary DPPC/ di(18:2)PC/cholesterol 0.42:0.28:0.3 mixture phase-separated into nanoscale raft-like liquid-ordered (Lo) and non-raft liquid-disordered (Ld) phases on a sub-microsecond time scale. The Lo domains were preferentially localized at planar portions, whereas the Ld domains were positioned mainly in curved regions of the membrane. Unlike binary dioleoylphosphatidylcho-line (DOPC)/cholesterol and DPPC/cholesterol mixtures, which showed only a slight enrich ment of cholesterol in the curved region, the ternary mixtures showed considerable migra tion of cholesterol and DPPC from the curved to the planar region. A pronounced degree of lipid segregation due to the preferential distribution of the Ld and Lo domains in the curved and planar regions, respectively, was observed even when the curvature of the fused monolayers (originally ‘cis’ leaflets) was weakened (C= –0.5 nm-1). Overall, the results are consistent with theoretical predictions based on spontaneous curvature of the constituent lipids and the difference in rigidity between the Ld and Lo domains, whereas lipid-lipid interactions, such as PE-PE or DPPC-cholesterol, as well as propensity fo

关键词： Lipid Raft Stalk Formation Membrane Rigidity Lipid Clustering Lipid Sorting Lipid Mixing Hemifusion Cholesterol-Rich Microdomain

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Curvature-driven lipid sorting: coarse-grained dynamics simulations of a membrane mimicking a hemifusion intermediate

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Journal of Biophysical Chemistry 2010年第2期1卷 86-95页

作者： manami nishizawa Kazuhisa nishizawa 不详

How membrane curvature influences lipid distribution is under intensive research. In this short report, after a brief review of recent studies, the results of our coarse-grained (CG) molecular dynamics simulations of membranes with “hemifused ribbons” geometry are discussed. When membranes of a binary mixture of (dipalmitoyl-phosphatidylcholine (DPPC) / diol-eoyl-phosphatidylethanolamine (DOPE) were used, DOPE accumulated in the negatively curved region of the monolayer that formed as the proximal monolayers fused (i.e., cis leaflets). However, the enrichment was dependent on the presence of tethering molecules which kept the curvature high (the curvature radius of ~1 nm), placing the cis monolayers ~2-2.5 nm from each other. Simulations in which DOPE was replaced with dioleoyl-phosphatidylcholine (DOPC) showed an insignificant degree of DOPC accumulation, suggesting the importance of lateral interaction among DOPE molecules for the curvature sorting. The above composition was not close to a demixing point and our radial distribution function analysis suggested that the DOPE accumulation was not assisted by the lipid phase separation which has been shown to promote curvature-driven lipid sorting. Relevance of curvature-driven lipid sorting to biological membrane fusion is discussed.

关键词： Membrane Fusion Raft Membrane Domain Cholesterol Lipid Phase Separation

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Molecular dynamics simulation analyses of viral fusion peptides in membranes prone to phase transition: effects on membrane curvature, phase behavior and lipid-water interface destabilization

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Journal of Biophysical Chemistry 2010年第1期1卷 19-32页

作者： manami nishizawa Kazuhisa nishizawa Department of Laboratory Medicine School of Medical Technology Teikyo University Tokyo Japan

To gain insight into the atomistic details of membrane fusion induced by fusogenic peptides, molecular dynamic simulations of synthetic peptides, derived from viral fusion proteins, contained in lipid bilayers were performed. A 20 amino acid peptide from the N-terminus of the influenza HA fusion peptide (WT20) assumed the oblique orientation at the interface between water and the membrane made up of dipalmitoylphosphatidylcholine (DPPC)/palmitic acid (PA), as reported previously for different membranes. Simulations of WT20 embedded in bilayer membranes made up of dioleoylphos-phatidylethanolamine (DOPE) and DPPC/PA showed a positive curvature-inducing effect, whereas WT20 showed a negative curvature-inducing effect on a DPPC bilayer. In phase re-constitution analyses starting from a random mixture of DPPC, PA and water molecules, WT20 weakly stabilized an inverted hexagonal phase. In the latter analyses WT20 preferentially assumed a transmembrane orientation as opposed to the interfacial orientation, regardless of the phase to which the system settled (lamellar vs. inverted hexagonal). In another set of analyses using systems containing a water layer between the apposed DPPC/PA (and DOPE) monolayers, the behavior of WT20 during the formation of an intermembrane connection (or stalk) was examined. Comparison among the mutants supports a view that the oblique orientation of WT20 facilitates the perturbation of the lipid-water interface and the stalk formation. Taken together, these results imply that the influenza HA fusion peptide can have substantial effects on the membrane curvature and can assume a wide range of orientation/position in membranes depending on the local environment of the lipid/water system. Its movability and oblique orientation appear to be associated with its ability to perturb membrane/water interfaces.

关键词： Molecular Simulation Fusion Peptide Stalk Formation Lipid Mixing Hemifusion

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Topic highlight on texture and color enhancement imaging in gastrointestinal diseases

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World Journal of Gastroenterology 2024年第14期30卷 1934-1940页

作者： Osamu Toyoshima Toshihiro nishizawa Keisuke Hata Department of Gastroenterology Toyoshima Endoscopy ClinicTokyo 157-0066Japan Department of Gastroenterology and Hepatology International University of Health and WelfareNarita HospitalNarita 286-8520Japan Department of Gastroenterology Nihonbashi Muromachi Mitsui Tower Midtown ClinicTokyo 103-0022Japan

Olympus Corporation developed texture and color enhancement imaging(TXI)as a novel image-enhancing endoscopic *** topic highlights a series of hot-topic articles that investigated the efficacy of TXI for gastrointestinal disease identification in the clinical setting.A randomized controlled trial demonstrated improvements in the colorectal adenoma detection rate(ADR)and the mean number of adenomas per procedure(MAP)of TXI compared with those of white-light imaging(WLI)observation(58.7%vs 42.7%,adjusted relative risk 1.35,95%CI:1.17-1.56;1.36 vs 0.89,adjusted incident risk ratio 1.48,95%CI:1.22-1.80,respectively).A cross-over study also showed that the colorectal MAP and ADR in TXI were higher than those in WLI(1.5 vs 1.0,adjusted odds ratio 1.4,95%CI:1.2-1.6;58.2%vs 46.8%,1.5,1.0-2.3,respectively).A randomized controlled trial demonstrated non-inferiority of TXI to narrow-band imaging in the colorectal mean number of adenomas and sessile serrated lesions per procedure(0.29 vs 0.30,difference for non-inferiority-0.01,95%CI:-0.10 to 0.08).A cohort study found that scoring for ulcerative colitis severity using TXI could predict relapse of ulcerative colitis.A cross-sectional study found that TXI improved the gastric cancer detection rate compared to WLI(0.71%vs 0.29%).A cross-sectional study revealed that the sensitivity and accuracy for active Helicobacter pylori gastritis in TXI were higher than those of WLI(69.2%vs 52.5%and 85.3%vs 78.7%,res-pectively).In conclusion,TXI can improve gastrointestinal lesion detection and qualitative ***,further studies on the efficacy of TXI in clinical practice are required.

关键词： Endoscopy Texture and color enhancement imaging White-light imaging Narrow-band imaging Colorectal neoplasm Gastric cancer Adenoma Ulcerative colitis Helicobacter infections Colonoscopy

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On the Impairment of Stress-Induced Changes in Triglyceride Levels via a Sub-Toxic Dose of Unmethylated Cytidine Phosphate Guanosine Oligodinucleotide (a Toll-Like Receptor 9 Ligand)

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Journal of Biosciences and Medicines 2024年第9期12卷 95-112页

作者： Reiko Seki Kazuhisa nishizawa School of Medical Technology Teikyo University Tokyo Japan Biomolecular Logic Research Laboratory Tokyo Japan Kamiikedai Laboratory Tokyo Japan

Changes in lipid metabolism have been implicated in protection against infectious diseases. In the first experiment of this study, we measured clinical lipid parameters in a murine model where the unmethylated cytidine phosphate guanosine (CpG) oligodinucleotide (ODN1826), a Toll-like receptor 9 (TLR9) agonist was administered in combination with D-galactosamine (GalN) that caused relatively liver-specific inflammation and toxicity. In the control mice group injected with phosphate-buffered saline (PBS) (acute psychological stress model associated with blood sampling), the serum triglyceride (TG) levels showed a rapid decrease followed by a rebound at 24 h as we have recently reported. However, such a TG rebound was impaired in the CpG/GalN- and solely CpG-treated groups of mice despite an absence of liver injury based on serum alanine aminotransferase levels in the latter group. Thus, the stress-associated serum TG rebound was abrogated by the injection of a sub-hepatotoxic CpG dose. In the second experiment, we simply measured the hepatic CD36 and SACRB1 (the gene for scavenger receptor B1 (SR-B1)) transcripts after the i.p. administration of PBS, CpG or CpG/GalN. There was a remarkable elevation of hepatic CD36 transcript expression in both the CpG- and CpG/GalN-treated mice at 8 h post-CpG injection whereas the increase in the PBS-treated mice was slower than the former two groups, suggesting that hepatic CD36 transcript expression is more pronounced in the combined stress models than under psychological stress alone. The individual mice data showed that the increase in CD36 expression was accompanied by a reduction in SCARB1 mRNA, showing reciprocal regulation between these two genes. Together with our previously reported findings, these data suggest that, in a murine model combining psychological stress with TLR-triggered hepatic inflammation, the psychological stress facilitates liver uptake of plasma TG (and its components fatty acids), but the subsequent re

关键词： Toll-Like Receptor 9 Cytidine Phosphate Guanosine Oligodinucleotide Scavenger Receptor B1 Triglyceride Hepatic Inflammation

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HISTORY AND RECENT DEVELOPMENTS OF TERAHERTZ WAVE GENERATION

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Acta Metallurgica Sinica(English Letters) 2003年第3期16卷 231-236页

作者： J.nishizawa Director of Photodynamics Research Center and Semiconductor Research Institute 5199-1399 Aramaki Aoba-kuSendai 980-0845 Japan

The unexplored terahertz (THz) region involves important phenomena of both fundamental and applied natures. Examples include phonon interactions, rotational transitions and intermolecular dynamics. Frequency tunable high power THz wave generation has been successfully achieved utilizing lattice resonance of LiNbO3 and GaP crystals, respectively. Semiconductor devices utilizing electron tunneling effect have also been developed.

关键词： THz wave generation phonon interaction semiconductor device

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Phase Equilibria in Ni Rich Region of Ni-Al-Fe System

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International Journal of Minerals,Metallurgy and Materials 2000年第4期14卷 277-281页

作者： Chengchang Jia Kiyohito Ishida Taiji nishizawa Material Science and Engineering School University of Science and Technology BeijingBeijing 100083China Engineering faculty Tohoku UniversitySendai 980Japan

The phase equilibria between γ, α, γ' and β in the Ni-rich region of the Ni-Al-Fe system were investigated by the diffusion couple method and thermodynamic models. The thermodynamic parameters were assessed based on experimental results and thermodynamic data. Moreover, the system's phase equilibria from 900 to 1 300℃ were calculated with regular solution and sublattice models, and it is shown that the theoretic results agree well with experimental phase diagram data.

关键词： Superalloys

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Kyoto classification of gastritis:Advances and future perspectives in endoscopic diagnosis of gastritis

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World Journal of Gastroenterology 2022年第43期28卷 6078-6089页

作者： Osamu Toyoshima Toshihiro nishizawa Department of Gastroenterology Toyoshima Endoscopy ClinicTokyo 157-0066Japan Department of Gastroenterology and Hepatology International University of Medicine and WelfareNarita 286-8520Japan

This editorial provides an update of the recent evidence on the endoscopy-based Kyoto classification of gastritis,clarifying the shortcomings of the Kyoto classification,and providing prospects for future research,with particular focus on the histological subtypes of gastric cancer(GC)and Helicobacter pylori(***)infection *** total Kyoto score is designed to express GC risk on a score ranging from 0 to 8,based on the following five endoscopic findings:Atrophy,intestinal metaplasia(IM),enlarged folds(EF),nodularity,and diffuse redness(DR).The total Kyoto score reflects *** status as follows:0,≥2,and≥4 indicate a normal stomach,***-infected gastritis,and gastritis at risk for GC,*** arrangement of collecting venules(RAC)predicts noninfection;EF,nodularity,and DR predict current infection;map-like redness(MLR)predicts past infection;and atrophy and IM predict current or past ***,IM,and EF all increase the incidence of ***-infected *** is a specific risk factor for ***-eradicated GC,while RAC results in less ***-type GC can be induced by active inflammation,which presents as EF,nodularity,and atrophy on endoscopy,as well as neutrophil and mononuclear cell infiltration on *** contrast,intestinal-type GC develops via atrophy and IM,and is consistent between endoscopy and ***,this GC risk-scoring design needs to be improved.

关键词： Kyoto classification Gastritis Endoscopy Gastric cancer Histology Helicobacter pylori

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The relationship between individual seed quality and maternal plant body size in crowded herbaceous vegetation

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Journal of Plant Ecology 2014年第4期7卷 330-336页

作者： Tomo nishizawa Lonnie W.Aarssen Department of Biology Queen’s UniversityKingstonOntario K7L 3N6Canada

Aims In most natural plant populations,there is a strong right-skewed dis-tribution of body sizes for reproductive *** vast majority are relatively small,suppressed weaklings that manage not just to survive effects of crowding/competition and other hazards but also to produce *** research has shown that because of their relatively large numbers,these relatively small resident plants collectively contribute most of the seed offspring production available for the population in the next ***,the success of these offspring will depend in part on their quality,*** by seed size and resource ***,in the present study,we used material from natural populations of herbaceous species to test the null hypothesis that there is no significant relationship between body size variation in resident plants-resulting from between-site variation in the intensity of crowding/competition-and variation in the mass or N content of their individual *** using populations of 56 herbaceous species common in eastern ontario,total above-ground dry plant mass,mean mass per seed and mean nitrogen(N)content per seed were recorded for a sample of the largest resident plants and also for the smallest reproduc-tive plants growing in local neighbourhoods with the most severe crowding/competition from near *** Findingsmass per seed was numerically smaller from the smallest resident plants for most study species,but with few exceptions,this was not significantly different(P>0.05)from mass per seed from the larg-est resident *** results therefore showed no general effect of maternal plant body size on individual seed mass,or N *** suggests that the reproductive output of the smaller half of the resident plant size distribution within these populations is likely to contribute not just most of the seed production available for the next generation but also seed offspring that are just as likely-on a per i

关键词： crowding competition plant size reproductive economy seed mass seed N content

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Endoscopic Kyoto classification of Helicobacter pylori infection and gastric cancer risk diagnosis

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World Journal of Gastroenterology 2020年第5期26卷 466-477页

作者： Osamu Toyoshima Toshihiro nishizawa Kazuhiko Koike Department of Gastroenterology Toyoshima Endoscopy ClinicTokyo 157-0066Japan Department of Gastroenterology Graduate School of MedicineThe University of TokyoTokyo 113-8655Japan Department of Gastroenterology and Hepatology International University of Health and WelfareMita HospitalTokyo 108-8329Japan

Recent advances in endoscopic technology allow detailed observation of the gastric ***,endoscopy is used in the diagnosis of gastritis to determine the presence/absence of Helicobacter pylori(***)infection and evaluate gastric cancer *** 2013,the Japan Gastroenterological Endoscopy Society advocated the Kyoto classification,a new grading system for endoscopic *** Kyoto classification organized endoscopic findings related to *** *** Kyoto classification score is the sum of scores for five endoscopic findings(atrophy,intestinal metaplasia,enlarged folds,nodularity,and diffuse redness with or without regular arrangement of collecting venules)and ranges from 0 to ***,intestinal metaplasia,enlarged folds,and nodularity contribute to gastric cancer *** redness and regular arrangement of collecting venules are related to *** infection *** subjects without a history of *** eradication,the infection rates in those with Kyoto scores of 0,1,and≥2 were 1.5%,45%,and 82%,respectively.A Kyoto classification score of 0 indicates no *** infection.A Kyoto classification score of 2 or more indicates *** *** classification scores of patients with and without gastric cancer were 4.8 and 3.8,respectively.A Kyoto classification score of 4 or more might indicate gastric cancer risk.

关键词： Gastric cancer Helicobacter pylori Endoscopy Kyoto classification Atrophy Intestinal metaplasia Enlarged fold Nodularity Diffuse redness Regular arrangement of collecting venules

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