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881.
Noriaki Okimoto Atsushi Suenaga Makoto Taiji 《Journal of biomolecular structure & dynamics》2017,35(15):3221-3231
In computational drug design, ranking a series of compound analogs in a manner that is consistent with experimental affinities remains a challenge. In this study, we evaluated the prediction of protein–ligand binding affinities using steered molecular dynamics simulations. First, we investigated the appropriate conditions for accurate predictions in these simulations. A conic harmonic restraint was applied to the system for efficient sampling of work values on the ligand unbinding pathway. We found that pulling velocity significantly influenced affinity predictions, but that the number of collectable trajectories was less influential. We identified the appropriate pulling velocity and collectable trajectories for binding affinity predictions as 1.25 Å/ns and 100, respectively, and these parameters were used to evaluate three target proteins (FK506 binding protein, trypsin, and cyclin-dependent kinase 2). For these proteins using our parameters, the accuracy of affinity prediction was higher and more stable when Jarzynski’s equality was employed compared with the second-order cumulant expansion equation of Jarzynski’s equality. Our results showed that steered molecular dynamics simulations are effective for predicting the rank order of ligands; thus, they are a potential tool for compound selection in hit-to-lead and lead optimization processes. 相似文献
882.
The sprouting of immature bulbils of Laportea bulbifera andpartially dormant (in-sufficiently chilled) mature bulbils ofL. bulbifera, Elatostema involucratum and E. umbellatum waspromoted by inhibitors of nucleic acid and protein synthesis(8-azaguanine, 5-fluorouracil, 2-thiouracil, ethionine, canavaninesulfate, p-fluorophenylalanine and cycloheximide in Laporteaand 5-fluorouracil, cycloheximide and chloramphenicol in Elatostema).However, the sprouting of nondormant (chilled) mature bulbilsof L. bulbifera was not promoted, but slightly suppressed whenthese inhibitors (especially, 8-azaguanine, cycloheximide andchloramphenicol) were applied either during or after chillingtreatment These results suggest that the two counteracting systems,dormancy-inducing and -breaking which involve nucleic acid andprotein synthesis participate in the dormancy regulation. (Received December 2, 1977; ) 相似文献
883.
Noriaki Kamio Sumio Akifusa Noboru Yamaguchi Kazuaki Nonaka & Yoshihisa Yamashita 《FEMS immunology and medical microbiology》2009,56(3):241-247
Adiponectin is an adipokine with potent anti-inflammatory properties. We previously reported that a globular adiponectin (gAd) suppresses Aggregatibacter actinomycetemcomitans lipopolysaccharide-induced nuclear factor-κB activity, suggesting an anti-inflammatory effect of gAd. In this study, we investigated whether gAd is able to modulate the effect of A. actinomycetemcomitans lipopolysaccharide on cytokine induction in a murine macrophage cell line (RAW 264). The phosphorylation of p38 mitogen-activated protein kinase, c-Jun N-terminal kinase, extracellular signal-regulated kinase, and IκB kinase α/β and the degradation of IκB, which were induced by A. actinomycetemcomitans lipopolysaccharide intoxication, were clearly reduced in gAd-pretreated RAW 264 cells compared with the untreated cells. Expression levels of tumor necrosis factor (TNF)-α and interleukin-10 (IL-10) mRNA were assessed by real-time PCR. Cell-free supernatants were collected after 12 h of stimulation and analyzed by enzyme-linked immunosorbent assay for TNF-α and IL-10. Pretreatment with gAd significantly inhibited the A. actinomycetemcomitans lipopolysaccharide-induced TNF-α mRNA expression and protein secretion. In contrast, pretreatment with gAd significantly enhanced the A. actinomycetemcomitans lipopolysaccharide-induced IL-10 mRNA expression and protein secretion. These data suggest a mechanism for the anti-inflammatory activity of gAd in local inflammatory lesions, such as periodontitis. 相似文献
884.
Haruo Kozono Yufuku Matsushita Naoki Ogawa Yuko Kozono Toshihiro Miyabe Hiroshi Sekiguchi Kouhei Ichiyanagi Noriaki Okimoto Makoto Taiji Osami Kanagawa Yuji?C. Sasaki 《Biophysical journal》2015,108(2):350-359
The major histocompatibility complex (MHC) class II protein can bind peptides of different lengths in the region outside the peptide-binding groove. Peptide-flanking residues (PFRs) contribute to the binding affinity of the peptide for MHC and change the immunogenicity of the peptide/MHC complex with regard to T cell receptor (TCR). The mechanisms underlying these phenomena are currently unknown. The molecular flexibility of the peptide/MHC complex may be an important determinant of the structures recognized by certain T cells. We used single-molecule x-ray analysis (diffracted x-ray tracking (DXT)) and fluorescence anisotropy to investigate these mechanisms. DXT enabled us to monitor the real-time Brownian motion of the peptide/MHC complex and revealed that peptides without PFRs undergo larger rotational motions than peptides with PFRs. Fluorescence anisotropy further revealed that peptides without PFRs exhibit slightly larger motions on the nanosecond timescale. These results demonstrate that peptides without PFRs undergo dynamic motions in the groove of MHC and consequently are able to assume diverse structures that can be recognized by T cells. 相似文献
885.
Tamura Noriaki; Noda Kosaku; Wakamatsu Kunimitsu; Kamachi Hiroyuki; Inoue Hiroshi; Wada Keishiro 《Plant & cell physiology》1997,38(5):578-585
Involvement of residues of acidic amino acids in photo-ligationof manganese into the apo-water-oxidizing complex was investigatedby use of l-ethyl-3-[3-(dimethylami-no)propyl]carbodiimide (EDC),a water-soluble carboxyl modifier. Treatment of Mn-depletedPSII membranes by EDC in the presence of nucleophiles induceda loss of photoactivation capability in the Mn complex and partialloss of capability of photooxidation of Mn2+, but little decreasein the DCIP photoreduction supported by diphen-ylcarbazide.The inhibition of diphenylcarbazide-photo-oxidation by submicromolarMn2+, indicative of the intactness of high-affinity Mn-bindingsites, was apparently abolished by EDC treatment. From aminoacid quantitation analysis of Dl and D2 proteins and CP47 ofthe chemically-modified membranes, approximately three carboxylgroups of the D1 protein were found to be chemically-modifiedwith EDC after removal of the functional Mn. These results suggestthat acidic amino acids on the D1 protein are involved in photoactivationof the apo-water-oxidizing complex and probably in ligationof Mn to the water-oxidizing complex. (Received October 21, 1996; Accepted March 3, 1997) 相似文献
886.
Shimazaki Ken-ichiro; Ito Kuniko; Kondo Noriaki; Sugahara Kiyoshi 《Plant & cell physiology》1984,25(5):795-803
The effect of SO2 fumigation (2 ppm, v/v) on photosynthesisin spinach leaves in vivo was investigated by measuring Chla fluorescence (OIDP transient) and the electron paramagneticresonance (EPR) signal I. SO2 fumigation raised the I levelto yield the ID dip and suppressed the DP transient before anyvisible damage occurred in the leaf. In SO2-fumigated leaves,the time course of EPR signal I indicates that reduction ofP700 by white light illumination was inhibited but dark reductionof P700 was not significantly affected. Photosynthetic O2 evolutionwas also inhibited by SO2 fumigation. All of these effects werereversible after removal of SO2. The variable part of the fluorescencein the presence of DCMU was only slightly affected and decreasedas the fumigation time increased. We concluded that SO2 fumigationreversibly inhibits the photosynthetic water-splitting enzymesystem and it injures the reaction center of PS II in vivo whenthe fumigation time is prolonged. We discussed the role of possible toxicants derived from SO2within the leaf on the basis of the SO2 action on Chl a fluorescence. (Received December 8, 1983; Accepted May 7, 1984) 相似文献
887.
888.
Yuki Matsushita Wanida Ono Noriaki Ono 《BioEssays : news and reviews in molecular, cellular and developmental biology》2021,43(1)
An emerging concept is that quiescent mature skeletal cells provide an important cellular source for bone regeneration. It has long been considered that a small number of resident skeletal stem cells are solely responsible for the remarkable regenerative capacity of adult bones. However, recent in vivo lineage‐tracing studies suggest that all stages of skeletal lineage cells, including dormant pre‐adipocyte‐like stromal cells in the marrow, osteoblast precursor cells on the bone surface and other stem and progenitor cells, are concomitantly recruited to the injury site and collectively participate in regeneration of the damaged skeletal structure. Lineage plasticity appears to play an important role in this process, by which mature skeletal cells can transform their identities into skeletal stem cell‐like cells in response to injury. These highly malleable, long‐living mature skeletal cells, readily available throughout postnatal life, might represent an ideal cellular resource that can be exploited for regenerative medicine. 相似文献
889.
Ethylene evolution in marine algae and a proteinaceous inhibitor of ethylene biosynthesis from red alga 总被引:1,自引:0,他引:1
Fronds of marine algae, especially green alga, Codium latum,and red alga, Porphyra tenera, evolved a quantity of ethylenewhen IAA was exogenously applied, while brown alga, Padina arborescens,evolved only a little. Propionic acid, when added together withIAA, noticeably enhanced IAA-induced ethylene evolution in P.tenera and P. arborescens. This evolution was also enhancedby added acrylic acid in P. arborescens but not in P. tenera.It was promoted by methionine, though only at a high concentration(0.1 M), in P. tenera but not in P. arborescens. The rate ofethylene evolution was highest at 12?C among the incubationtemperatures tested of 5, 12 and 15?C. The conversion of 14C-3-methionineto radioactive ethylene in P. tenera was remarkably inhibitedby a proteinaceous inhibitor from P. tenera.
1Present address: Division of Environmental Biology, NationalInstitute for Environment, Yatabe, Ibaraki, Japan. (Received May 27, 1976; ) 相似文献
890.
Takumi Itoh Ryo Hatano Yoshiya Horimoto Taketo Yamada Dan Song Haruna Otsuka Yuki Shirakawa Shuji Mastuoka Noriaki Iwao Thomas M. Aune Nam H. Dang Yutaro Kaneko Ko Okumura Chikao Morimoto Kei Ohnuma 《Cell death & disease》2021,12(6)
Triple-negative breast cancer (TNBC) has a poor prognosis compared to other breast cancer subtypes. Although epidermal growth factor receptor (EGFR) is overexpressed in TNBC, clinical trials with EGFR inhibitors including tyrosine kinase inhibitors (EGFR-TKI) in TNBC have heretofore been unsuccessful. To develop effective EGFR-targeted therapy for TNBC, the precise mechanisms of EGFR-TKI resistance in TNBC need to be elucidated. In this study, to understand the molecular mechanisms involved in the differences in EGFR-TKI efficacy on TNBC between human and mouse, we focused on the effect of IL-26, which is absent in mice. In vitro analysis showed that IL-26 activated AKT and JNK signaling of bypass pathway of EGFR-TKI in both murine and human TNBC cells. We next investigated the mechanisms involved in IL-26-mediated EGFR-TKI resistance in TNBC. We identified EphA3 as a novel functional receptor for IL-26 in TNBC. IL-26 induced dephosphorylation and downmodulation of EphA3 in TNBC, which resulted in increased phosphorylation of AKT and JNK against EGFR-TKI-induced endoplasmic reticulum (ER) stress, leading to tumor growth. Meanwhile, the blockade of IL-26 overcame EGFR-TKI resistance in TNBC. Since the gene encoding IL-26 is absent in mice, we utilized human IL-26 transgenic (hIL-26Tg) mice as a tumor-bearing murine model to characterize the role of IL-26 in the differential effect of EGFR-TKI in human and mice and to confirm our in vitro findings. Our findings indicate that IL-26 activates the bypass pathway of EGFR-TKI, while blockade of IL-26 overcomes EGFR-TKI resistance in TNBC via enhancement of ER stress signaling. Our work provides novel insights into the mechanisms of EGFR-TKI resistance in TNBC via interaction of IL-26 with its newly identified receptor EphA3, while also suggesting IL-26 as a possible therapeutic target in TNBC.Subject terms: Stress signalling, Cell death and immune response, Breast cancer 相似文献