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Article ; Online: Evaluation of the context of downstream N- and free N-glycomic alterations induced by swainsonine in HepG2 cells.

Morikawa, Chie / Sugiura, Kanako / Kondo, Keina / Yamamoto, Yurie / Kojima, Yuma / Ozawa, Yurika / Yoshioka, Hiroki / Miura, Nobuaki / Piao, Jinhua / Okada, Kazue / Hanamatsu, Hisatoshi / Tsuda, Masumi / Tanaka, Shinya / Furukawa, Jun-Ichi / Shinohara, Yasuro

Biochimica et biophysica acta. General subjects

2022 Volume 1866, Issue 9, Page(s) 130168

Abstract: ... that occur in N- and free N-glycomic upon addition of SWA to HepG2 cells to understand better SWA-induced ... such as unique fucosylated hybrid-type and fucosylated M5 (M5F) N-glycans, and a remarkable increase ... that (fucosylated) hybrid type N-glycans were not the precursors of these Gn1 FNGs and vice versa. Time course ...

Abstract	Swainsonine (SWA), a potent inhibitor of class II α-mannosidases, is present in a number of plant species worldwide and causes severe toxicosis in livestock grazing these plants. The mechanisms underlying SWA-induced animal poisoning are not fully understood. In this study, we analyzed the alterations that occur in N- and free N-glycomic upon addition of SWA to HepG2 cells to understand better SWA-induced glycomic alterations. After SWA addition, we observed the appearance of SWA-specific glycomic alterations, such as unique fucosylated hybrid-type and fucosylated M5 (M5F) N-glycans, and a remarkable increase in all classes of Gn1 FNGs. Further analysis of the context of these glycomic alterations showed that (fucosylated) hybrid type N-glycans were not the precursors of these Gn1 FNGs and vice versa. Time course analysis revealed the dynamic nature of glycomic alterations upon exposure of SWA and suggested that accumulation of free N-glycans occurred earlier than that of hybrid-type N-glycans. Hybrid-type N-glycans, of which most were uniquely core fucosylated, tended to increase slowly over time, as was observed for M5F N-glycans. Inhibition of swainsonine-induced unique fucosylation of hybrid N-glycans and M5 by coaddition of 2-fluorofucose caused significant increases in paucimannose- and fucosylated paucimannose-type N-glycans, as well as paucimannose-type free N-glycans. The results not only revealed the gross glycomic alterations in HepG2 cells induced by swainsonine, but also provide information on the global interrelationships between glycomic alterations.
MeSH term(s)	Animals ; Glycomics ; Glycosylation ; Hep G2 Cells ; Humans ; Polysaccharides ; Swainsonine/toxicity
Chemical Substances	Polysaccharides ; Swainsonine (RSY4RK37KQ)
Language	English
Publishing date	2022-05-17
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	60-7
ISSN	1872-8006 ; 1879-2596 ; 1879-260X ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1872-8006 ; 1879-2596 ; 1879-260X ; 1879-2642 ; 1879-2618 ; 1879-2650
ISSN	0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/j.bbagen.2022.130168
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Article ; Online: Study of the N=32 and N=34 Shell Gap for Ti and V by the First High-Precision Multireflection Time-of-Flight Mass Measurements at BigRIPS-SLOWRI.

Iimura, S / Rosenbusch, M / Takamine, A / Tsunoda, Y / Wada, M / Chen, S / Hou, D S / Xian, W / Ishiyama, H / Yan, S / Schury, P / Crawford, H / Doornenbal, P / Hirayama, Y / Ito, Y / Kimura, S / Koiwai, T / Kojima, T M / Koura, H /

Lee, J / Liu, J / Michimasa, S / Miyatake, H / Moon, J Y / Naimi, S / Nishimura, S / Niwase, T / Odahara, A / Otsuka, T / Paschalis, S / Petri, M / Shimizu, N / Sonoda, T / Suzuki, D / Watanabe, Y X / Wimmer, K / Wollnik, H

Physical review letters

2023 Volume 130, Issue 1, Page(s) 12501

Abstract: ... keV, shedding new light on the N=34 shell effect in Ti and V isotopes by the first high-precision mass ... the nonexistence of the N=34 empirical two-neutron shell gaps for Ti and V, and the enhanced energy gap above ... at N=34. ...

Abstract	The atomic masses of ^{55}Sc, ^{56,58}Ti, and ^{56-59}V have been determined using the high-precision multireflection time-of-flight technique. The radioisotopes have been produced at RIKEN's Radioactive Isotope Beam Factory (RIBF) and delivered to the novel designed gas cell and multireflection system, which has been recently commissioned downstream of the ZeroDegree spectrometer following the BigRIPS separator. For ^{56,58}Ti and ^{56-59}V, the mass uncertainties have been reduced down to the order of 10 keV, shedding new light on the N=34 shell effect in Ti and V isotopes by the first high-precision mass measurements of the critical species ^{58}Ti and ^{59}V. With the new precision achieved, we reveal the nonexistence of the N=34 empirical two-neutron shell gaps for Ti and V, and the enhanced energy gap above the occupied νp_{3/2} orbit is identified as a feature unique to Ca. We perform new Monte Carlo shell model calculations including the νd_{5/2} and νg_{9/2} orbits and compare the results with conventional shell model calculations, which exclude the νg_{9/2} and the νd_{5/2} orbits. The comparison indicates that the shell gap reduction in Ti is related to a partial occupation of the higher orbitals for the outer two valence neutrons at N=34.
MeSH term(s)	Titanium ; Neutrons
Chemical Substances	Titanium (D1JT611TNE)
Language	English
Publishing date	2023-01-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	208853-8
ISSN	1079-7114 ; 0031-9007
ISSN (online)	1079-7114
ISSN	0031-9007
DOI	10.1103/PhysRevLett.130.012501
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Article ; Online: Plasma N-terminal pro-atrial natriuretic peptide concentrations are affected by dehydration in healthy dogs.

Ogawa, Mizuki / Kojima, Yuki / Ishizaka, Mio / Miyakawa, Hirosumi / Hsu, Huai-Hsun / Miyagawa, Yuichi / Takemura, Naoyuki

Open veterinary journal

2023 Volume 13, Issue 5, Page(s) 604–612

Abstract: Background: Plasma N-terminal pro-atrial natriuretic peptide (NT-proANP) and plasma N-terminal pro ...

Abstract	Background: Plasma N-terminal pro-atrial natriuretic peptide (NT-proANP) and plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations may be affected by the hydration status. Aim: This study aimed to evaluate the effect of dehydration on plasma NT-proANP and NT-proBNP concentrations in healthy dogs. Methods: This prospective study included five clinically healthy dogs. Furosemide was administered intravenously at 2-4 mg/kg every 1-2 hours until completion of the dehydration model. The dehydration model was considered complete when weight loss was ≥5% and findings of dehydration on physical examination were observed. Plasma NT-proANP and NT-proBNP concentrations were compared at three-time points: before the dehydration model was created (point 1), at the completion of the dehydration model (point 2), and when dehydration was judged to have improved (point 3). Association between plasma NT-proANP and NT-proBNP concentrations, and each clinical variable (physical examination, blood pressure, blood chemistry, blood gases, and echocardiography) was assessed using linear regression analysis. Results: Plasma NT-proANP concentration decreased significantly from point 2 to point 1 ( Conclusion: The plasma NT-proANP concentrations decreased with dehydration. However, the plasma NT-proBNP concentration did not change with mild dehydration and reflected left ventricular morphology.
MeSH term(s)	Animals ; Dogs ; Atrial Natriuretic Factor ; Dehydration/veterinary ; Prospective Studies ; Echocardiography ; Furosemide ; Dog Diseases
Chemical Substances	Atrial Natriuretic Factor (85637-73-6) ; Furosemide (7LXU5N7ZO5)
Language	English
Publishing date	2023-05-14
Publishing country	Libya
Document type	Journal Article
ZDB-ID	2651664-0
ISSN	2218-6050 ; 2218-6050
ISSN (online)	2218-6050
ISSN	2218-6050
DOI	10.5455/OVJ.2023.v13.i5.13
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Article ; Online: Oxytocin-induced increase in N,N-dimethylglycine and time course of changes in oxytocin efficacy for autism social core symptoms.

Kato, Yasuhiko / Kuwabara, Hitoshi / Okada, Takashi / Munesue, Toshio / Benner, Seico / Kuroda, Miho / Kojima, Masaki / Yassin, Walid / Eriguchi, Yosuke / Kameno, Yosuke / Murayama, Chihiro / Nishimura, Tomoko / Tsuchiya, Kenji / Kasai, Kiyoto / Ozaki, Norio / Kosaka, Hirotaka / Yamasue, Hidenori

Molecular autism

2021 Volume 12, Issue 1, Page(s) 15

Abstract: ... intranasal administration of oxytocin (48 IU/day) or placebo in adult males with ASD (N = 106) who participated in a multi ... Among the 35 metabolites measured, a significant increase in N,N-dimethylglycine was detected in the subjects ... corrected P = 0.043, d = 0.74, N = 83). Furthermore, subgroup analyses of the participants displaying ...

Abstract	Background: Oxytocin is expected as a novel therapeutic agent for autism spectrum disorder (ASD) core symptoms. However, previous results on the efficacy of repeated administrations of oxytocin are controversial. Recently, we reported time-course changes in the efficacy of the neuropeptide underlying the controversial effects of repeated administration; however, the underlying mechanisms remained unknown. Methods: The current study explored metabolites representing the molecular mechanisms of oxytocin's efficacy using high-throughput metabolomics analysis on plasma collected before and after 6-week repeated intranasal administration of oxytocin (48 IU/day) or placebo in adult males with ASD (N = 106) who participated in a multi-center, parallel-group, double-blind, placebo-controlled, randomized controlled trial. Results: Among the 35 metabolites measured, a significant increase in N,N-dimethylglycine was detected in the subjects administered oxytocin compared with those given placebo at a medium effect size (false discovery rate (FDR) corrected P = 0.043, d = 0.74, N = 83). Furthermore, subgroup analyses of the participants displaying a prominent time-course change in oxytocin efficacy revealed a significant effect of oxytocin on N,N-dimethylglycine levels with a large effect size (P Limitations: The metabolites changes caused by oxytocin administration were quantified using peripheral blood and therefore may not directly reflect central nervous system changes. Conclusion: Our findings demonstrate an association of N,N-dimethylglycine upregulation with the time-course change in the efficacy of oxytocin on autistic social deficits. Furthermore, the current findings support the involvement of the N-methyl-D-aspartate receptor and neural plasticity to the time-course change in oxytocin's efficacy. Trial registration: A multi-center, parallel-group, placebo-controlled, double-blind, confirmatory trial of intranasal oxytocin in participants with autism spectrum disorders (the date registered: 30 October 2014; UMIN Clinical Trials Registry: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000017703 ) (UMIN000015264).
MeSH term(s)	Administration, Intranasal ; Adolescent ; Adult ; Autistic Disorder/blood ; Autistic Disorder/drug therapy ; Autistic Disorder/metabolism ; Autistic Disorder/psychology ; Double-Blind Method ; Facial Expression ; Humans ; Male ; Metabolomics ; Middle Aged ; Oxytocin/administration & dosage ; Oxytocin/blood ; Oxytocin/pharmacokinetics ; Sarcosine/analogs & derivatives ; Sarcosine/blood ; Social Behavior ; Treatment Outcome ; Young Adult
Chemical Substances	Oxytocin (50-56-6) ; dimethylglycine (7797M4CPPA) ; Sarcosine (Z711V88R5F)
Language	English
Publishing date	2021-02-23
Publishing country	England
Document type	Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	2540930-X
ISSN	2040-2392 ; 2040-2392
ISSN (online)	2040-2392
ISSN	2040-2392
DOI	10.1186/s13229-021-00423-z
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Article ; Online: Approaching isotropic charge transport of n-type organic semiconductors with bulky substituents.

Yu, Craig P / Kojima, Naoya / Kumagai, Shohei / Kurosawa, Tadanori / Ishii, Hiroyuki / Watanabe, Go / Takeya, Jun / Okamoto, Toshihiro

Communications chemistry

2021 Volume 4, Issue 1, Page(s) 155

Abstract: Benzo[de]isoquinolino[1,8-gh]quinolinetetracarboxylic diimide (BQQDI) is an n-type organic ...

Abstract	Benzo[de]isoquinolino[1,8-gh]quinolinetetracarboxylic diimide (BQQDI) is an n-type organic semiconductor that has shown unique multi-fold intermolecular hydrogen-bonding interactions, leading to aggregated structures with excellent charge transports and electron mobility properties. However, the strong intermolecular anchoring of BQQDI presents challenges for fine-tuning the molecular assembly and improving the semiconducting properties. Herein, we report the design and synthesis of two BQQDI derivatives with phenyl- and cyclohexyl substituents (Ph-BQQDI and Cy
Language	English
Publishing date	2021-11-11
Publishing country	England
Document type	Journal Article
ZDB-ID	2929562-2
ISSN	2399-3669 ; 2399-3669
ISSN (online)	2399-3669
ISSN	2399-3669
DOI	10.1038/s42004-021-00583-2
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Article ; Online: Hydrogen bonds connecting the N-terminal region and the DE loop stabilize the monomeric structure of transthyretin.

Inada, Yuki / Ono, Yuichiro / Okazaki, Kyo / Yamashita, Takuma / Kawaguchi, Tomoyuki / Kawano, Shingo / Kobashigawa, Yoshihiro / Shinya, Shoko / Kojima, Chojiro / Shuto, Tsuyoshi / Kai, Hirofumi / Morioka, Hiroshi / Sato, Takashi

Journal of biochemistry

2023 Volume 174, Issue 4, Page(s) 355–370

Abstract: ... Here, we show that an N-terminal C10S mutation increases the thermodynamic stability of the TTR monomer ... loop. We propose that introducing hydrogen bonds to connect the N-terminal region to the DE loop ...

Abstract	Transthyretin (TTR) is a homo-tetrameric serum protein associated with sporadic and hereditary systemic amyloidosis. TTR amyloid formation proceeds by the dissociation of the TTR tetramer and the subsequent partial unfolding of the TTR monomer into an aggregation-prone conformation. Although TTR kinetic stabilizers suppress tetramer dissociation, a strategy for stabilizing monomers has not yet been developed. Here, we show that an N-terminal C10S mutation increases the thermodynamic stability of the TTR monomer by forming new hydrogen bond networks through the side chain hydroxyl group of Ser10. Nuclear magnetic resonance spectrometry and molecular dynamics simulation revealed that the Ser10 hydroxyl group forms hydrogen bonds with the main chain amide group of either Gly57 or Thr59 on the DE loop. These hydrogen bonds prevent the dissociation of edge strands in the DAGH and CBEF β-sheets during the unfolding of the TTR monomer by stabilizing the interaction between β-strands A and D and the quasi-helical structure in the DE loop. We propose that introducing hydrogen bonds to connect the N-terminal region to the DE loop reduces the amyloidogenic potential of TTR by stabilizing the monomer.
MeSH term(s)	Protein Conformation ; Hydrogen Bonding ; Prealbumin/chemistry ; Prealbumin/genetics ; Prealbumin/metabolism ; Molecular Dynamics Simulation ; Amyloid/chemistry ; Amyloid/metabolism
Chemical Substances	Prealbumin ; Amyloid
Language	English
Publishing date	2023-07-01
Publishing country	England
Document type	Journal Article
ZDB-ID	218073-x
ISSN	1756-2651 ; 0021-924X
ISSN (online)	1756-2651
ISSN	0021-924X
DOI	10.1093/jb/mvad049
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Article ; Online: A Mechanistic Dichotomy in Two-Electron Reduction of Dioxygen Catalyzed by N,N'-Dimethylated Porphyrin Isomers.

Suzuki, Wataru / Kotani, Hiroaki / Ishizuka, Tomoya / Kojima, Takahiko

Chemistry (Weinheim an der Bergstrasse, Germany)

2020 Volume 26, Issue 46, Page(s) 10480–10486

Abstract: Selective two-electron reduction of dioxygen ( ... ...

Abstract	Selective two-electron reduction of dioxygen (O
Language	English
Publishing date	2020-07-28
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1478547-X
ISSN	1521-3765 ; 0947-6539
ISSN (online)	1521-3765
ISSN	0947-6539
DOI	10.1002/chem.202000942
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Article ; Online: Crystal structure of N-terminal degron-truncated human glutamine synthetase.

Chek, Min Fey / Kim, Sun Yong / Mori, Tomoyuki / Kojima, Hisayuki / Hakoshima, Toshio

Acta crystallographica. Section F, Structural biology communications

2021 Volume 77, Issue Pt 11, Page(s) 427–434

Abstract: ... Acetylation of the N-terminal degron (N-degron) of GS is essential for ubiquitylation and subsequent GS ... degradation. The full-length GS structure showed that the N-degron is buried inside the GS decamer and is ... inaccessible to the acetyltransferase. The structure of N-degron-truncated GS reported here reveals that the N ...

Abstract	Glutamine synthetase (GS) is a decameric enzyme that plays a key role in nitrogen metabolism. Acetylation of the N-terminal degron (N-degron) of GS is essential for ubiquitylation and subsequent GS degradation. The full-length GS structure showed that the N-degron is buried inside the GS decamer and is inaccessible to the acetyltransferase. The structure of N-degron-truncated GS reported here reveals that the N-degron is not essential for GS decamer formation. It is also shown that the N-degron can be exposed to a solvent region through a series of conformational adjustments upon ligand binding. In summary, this study elucidated the dynamic movement of the N-degron and the possible effect of glutamine in enhancing the acetylation process.
MeSH term(s)	Crystallography, X-Ray ; Glutamate-Ammonia Ligase/chemistry ; Glutamate-Ammonia Ligase/genetics ; Glutamate-Ammonia Ligase/metabolism ; Glutamine/chemistry ; Humans ; Ubiquitination
Chemical Substances	Glutamine (0RH81L854J) ; GLUL protein, human (EC 6.3.1.2) ; Glutamate-Ammonia Ligase (EC 6.3.1.2)
Language	English
Publishing date	2021-10-29
Publishing country	United States
Document type	Journal Article
ISSN	2053-230X
ISSN (online)	2053-230X
DOI	10.1107/S2053230X21010748
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Article ; Online: Role of the N- and C-terminal regions of FliF, the MS ring component in

Kojima, Seiji / Kajino, Hiroki / Hirano, Keiichi / Inoue, Yuna / Terashima, Hiroyuki / Homma, Michio

Journal of bacteriology

2021 Volume 203, Issue 9

Abstract: ... of a large periplasmic region and two transmembrane segments connected to the N- and C-terminal regions ...

Abstract	The MS ring is a part of the flagellar basal body and formed by 34 subunits of FliF, which consists of a large periplasmic region and two transmembrane segments connected to the N- and C-terminal regions facing the cytoplasm. A cytoplasmic protein, FlhF, which determines the position and number of the basal body, supports MS ring formation in the membrane in
Language	English
Publishing date	2021-02-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	2968-3
ISSN	1098-5530 ; 0021-9193
ISSN (online)	1098-5530
ISSN	0021-9193
DOI	10.1128/JB.00009-21
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Article ; Online: Functional analysis of the N-terminal region of Vibrio FlhG, a MinD-type ATPase in flagellar number control.

Homma, Michio / Mizuno, Akira / Hao, Yuxi / Kojima, Seiji

Journal of biochemistry

2022 Volume 172, Issue 2, Page(s) 99–107

Abstract: ... in Vibrio alginolyticus. FlhG is a paralogue of the Escherichia coli cell division regulator MinD and has a longer N ... terminal region than MinD with a conserved DQAxxLR motif. The deletion of this N-terminal region or a Q9A ... causes a multi-flagellation phenotype. The mutant FlhG proteins, especially the N-terminally deleted variant ...

Abstract	GTPase FlhF and ATPase FlhG are two key factors involved in regulating the flagellum number in Vibrio alginolyticus. FlhG is a paralogue of the Escherichia coli cell division regulator MinD and has a longer N-terminal region than MinD with a conserved DQAxxLR motif. The deletion of this N-terminal region or a Q9A mutation in the DQAxxLR motif prevents FlhG from activating the GTPase activity of FlhF in vitro and causes a multi-flagellation phenotype. The mutant FlhG proteins, especially the N-terminally deleted variant, were remarkably reduced compared to that of the wild-type protein in vivo. When the mutant FlhG was expressed at the same level as the wild-type FlhG, the number of flagella was restored to the wild-type level. Once synthesized in Vibrio cells, the N-terminal region mutation in FlhG seems not to affect the protein stability. We speculated that the flhG translation efficiency is decreased by N-terminal mutation. Our results suggest that the N-terminal region of FlhG controls the number of flagella by adjusting the FlhF activity and the amount of FlhG in vivo. We speculate that the regulation by FlhG, achieved through transcription by the master regulator FlaK, is affected by the mutations, resulting in reduced flagellar formation by FlhF.
MeSH term(s)	Adenosine Triphosphatases/genetics ; Adenosine Triphosphatases/metabolism ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Flagella/metabolism ; Gene Expression Regulation, Bacterial ; Monomeric GTP-Binding Proteins/genetics ; Mutant Proteins/genetics ; Vibrio alginolyticus/genetics ; Vibrio alginolyticus/metabolism
Chemical Substances	Bacterial Proteins ; Mutant Proteins ; Adenosine Triphosphatases (EC 3.6.1.-) ; Monomeric GTP-Binding Proteins (EC 3.6.5.2)
Language	English
Publishing date	2022-06-07
Publishing country	England
Document type	Journal Article
ZDB-ID	218073-x
ISSN	1756-2651 ; 0021-924X
ISSN (online)	1756-2651
ISSN	0021-924X
DOI	10.1093/jb/mvac047
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