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Article ; Online: Increased RET Activity Coupled with a Reduction in the

Okamoto, Mitsumasa / Uesaka, Toshihiro / Ito, Keisuke / Enomoto, Hideki

2021 Volume 8, Issue 3

Abstract: Mutations of the gene encoding ... ...

Abstract	Mutations of the gene encoding the
MeSH term(s)	Animals ; Gene Dosage ; Glial Cell Line-Derived Neurotrophic Factor/genetics ; Hirschsprung Disease/genetics ; Humans ; Mice ; Mutation/genetics ; Proto-Oncogene Proteins c-ret/genetics
Chemical Substances	Glial Cell Line-Derived Neurotrophic Factor ; Proto-Oncogene Proteins c-ret (EC 2.7.10.1) ; RET protein, human (EC 2.7.10.1)
Language	English
Publishing date	2021-06-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	2800598-3
ISSN	2373-2822 ; 2373-2822
ISSN (online)	2373-2822
ISSN	2373-2822
DOI	10.1523/ENEURO.0534-20.2021
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Dynamic Electron Polarization Lasting More Than 10 μs by Hybridizing Porphyrin and TEMPO with Flexible Linkers.

Nishimura, Koki / Yabuki, Reiya / Hamachi, Tomoyuki / Kimizuka, Nobuo / Tateishi, Kenichiro / Uesaka, Tomohiro / Yanai, Nobuhiro

The journal of physical chemistry. B

2023 Volume 127, Issue 5, Page(s) 1219–1228

Abstract: Dynamic electron polarization (DEP), induced by quenching of photoexcited species by stable radicals, can hyperpolarize electron spins in solution at room temperature. Recently, development of technologies based on electron spin polarization such as ... ...

Abstract	Dynamic electron polarization (DEP), induced by quenching of photoexcited species by stable radicals, can hyperpolarize electron spins in solution at room temperature. Recently, development of technologies based on electron spin polarization such as dynamic nuclear polarization (DNP) has been progressing, where it is important to design molecules that achieve long-lasting DEP in addition to high DEP. Hybridization by linking dyes and radicals is a promising approach for efficient DEP, but strong interactions between neighboring dyes and radicals often result in the rapid decay of DEP. In this study, we introduce a flexible linker into the hybrid system of porphyrin and TEMPO to achieve both efficient DEP and long-lasting DEP. The structural flexibility of the linker switches the interaction between the radical and the triplet, which promotes the DEP process by bringing the radical and the triplet into close proximity, while avoiding abrupt relaxation due to strong interactions. As a result, the new hybridized system exhibits a larger DEP than the unlinked system, while at the same time achieving a DEP lasting more than 10 μs.
Language	English
Publishing date	2023-01-30
Publishing country	United States
Document type	Journal Article
ISSN	1520-5207
ISSN (online)	1520-5207
DOI	10.1021/acs.jpcb.2c07936
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Article ; Online: Polarizing agents beyond pentacene for efficient triplet dynamic nuclear polarization in glass matrices.

Sakamoto, Keita / Hamachi, Tomoyuki / Miyokawa, Katsuki / Tateishi, Kenichiro / Uesaka, Tomohiro / Kurashige, Yuki / Yanai, Nobuhiro

Proceedings of the National Academy of Sciences of the United States of America

2023 Volume 120, Issue 44, Page(s) e2307926120

Abstract: Triplet dynamic nuclear polarization (triplet-DNP) is a technique that can obtain high nuclear polarization under moderate conditions. However, in order to obtain practically useful polarization, large single crystals doped with a polarizing agent must ... ...

Abstract	Triplet dynamic nuclear polarization (triplet-DNP) is a technique that can obtain high nuclear polarization under moderate conditions. However, in order to obtain practically useful polarization, large single crystals doped with a polarizing agent must be strictly oriented with respect to the magnetic field to sharpen the electron spin resonance (ESR) spectra, which is a fatal problem that prevents its application to truly useful biomolecular targets. Instead of this conventional physical approach of controlling crystal orientation, here, we propose a chemical approach, i.e., molecular design of polarizing agents; pentacene molecules, the most typical triplet-DNP polarizing agent, are modified so as to make the triplet electron distribution wider and more isotropic without loss of the triplet polarization. The thiophene-modified pentacene exhibits a sharper and stronger ESR spectrum than the parent pentacene, and state-of-the-art quantum chemical calculations revealed that the direction of the spin polarization is altered by the modification with thiophene moieties and the size of
Language	English
Publishing date	2023-10-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2307926120
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Article: Synthesis and photophysical properties of photostable 1,8-naphthalimide dyes incorporating benzotriazole-based UV absorbers

Uesaka, Toshiyuki / Ishitani, Tomoyuki / Shimeno, Takahito / Suzuki, Naoya / Yagi, Shigeyuki / Maeda, Takeshi

RSC advances. 2022 June 13, v. 12, no. 27

2022

Abstract: We developed a series of blue-emitting 1,8-naphthalimide dyes covalently attached to 2-(2-hydroxyphenyl)-2H-benzotriazoles that retard photodegradation of the fluorophore. The dyes displayed weaker fluorescence emissions than the parent 1.8-naphthalimide. ...

Abstract	We developed a series of blue-emitting 1,8-naphthalimide dyes covalently attached to 2-(2-hydroxyphenyl)-2H-benzotriazoles that retard photodegradation of the fluorophore. The dyes displayed weaker fluorescence emissions than the parent 1.8-naphthalimide. Quantum chemical calculations suggested that the decreased fluorescence was caused by the nonradiative deactivation promoted through the excited state intramolecular proton transfer (ESIPT) in benzotriazole components. The dyes' phosphorescences in a degassed solution at 77 K were more efficient than that of the parent 1.8-naphthalimide, indicating a possible deactivation pathway through intersystem crossing. PMMA films doped with these dyes showed higher resistance against photoaging than the film doped with an equimolar mixture of constituent 1.8-naphthalimide and the benzotriazole derivatives. Thus, the covalently linked benzotriazole units slow fluorophore degradation not only by preferential absorption of harmful UV light, which is found in the film with a simple mixture of two components, but also by the nonradiative deactivation involved in benzotriazole units.
Keywords	absorption ; chemical bonding ; fluorescence ; fluorescent dyes ; photoaging ; photolysis ; quantum mechanics ; triazoles ; ultraviolet radiation
Language	English
Dates of publication	2022-0613
Size	p. 17350-17361.
Publishing place	The Royal Society of Chemistry
Document type	Article
ISSN	2046-2069
DOI	10.1039/d2ra02028a
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Microfluidics of imbibition in random porous media.

Wiklund, H S / Uesaka, T

Physical review. E, Statistical, nonlinear, and soft matter physics

2013 Volume 87, Issue 2, Page(s) 23006

Abstract: A free-energy lattice Boltzmann approach has been used to perform simulations of liquid penetration into random porous media. We focus our study on the effects of microstructures, particularly microtopography, on liquid penetration driven by capillary ... ...

Abstract	A free-energy lattice Boltzmann approach has been used to perform simulations of liquid penetration into random porous media. We focus our study on the effects of microstructures, particularly microtopography, on liquid penetration driven by capillary force and external pressure. For this purpose we set up a model structure that consists of a network of interconnected capillaries with varying pore geometries. The results showed that the discontinuities in the solid-surface curvature, as are present as corners on the capillary surfaces, have strong influences on liquid penetration through their pinning effects and interactions with local geometry.
MeSH term(s)	Computer Simulation ; Microfluidics/methods ; Models, Theoretical ; Porosity
Language	English
Publishing date	2013-02
Publishing country	United States
Document type	Journal Article
ISSN	1550-2376
ISSN (online)	1550-2376
DOI	10.1103/PhysRevE.87.023006
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Article ; Online: Synthesis and photophysical properties of photostable 1,8-naphthalimide dyes incorporating benzotriazole-based UV absorbers.

Uesaka, Toshiyuki / Ishitani, Tomoyuki / Shimeno, Takahito / Suzuki, Naoya / Yagi, Shigeyuki / Maeda, Takeshi

RSC advances

2022 Volume 12, Issue 27, Page(s) 17350–17361

Abstract: We developed a series of blue-emitting 1,8-naphthalimide dyes covalently attached to 2-(2-hydroxyphenyl)- ... ...

Abstract	We developed a series of blue-emitting 1,8-naphthalimide dyes covalently attached to 2-(2-hydroxyphenyl)-2
Language	English
Publishing date	2022-06-13
Publishing country	England
Document type	Journal Article
ISSN	2046-2069
ISSN (online)	2046-2069
DOI	10.1039/d2ra02028a
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Article ; Online: CD44 is critical for the enhancing effect of hyaluronan in allergen-specific sublingual immunotherapy in a murine model of chronic asthma.

Katoh, Shigeki / Uesaka, Tae / Tanaka, Hitomi / Matsuhara, Hiroki / Ohashi-Doi, Katsuyo / Oga, Toru

Clinical and experimental immunology

2022 Volume 208, Issue 2, Page(s) 202–211

Abstract: Allergen-specific sublingual immunotherapy (SLIT) is a potentially effective disease-modification treatment for patients with allergic asthma. Because CD44 signaling enhances regulatory T (Treg) cell-induction, administering CD44 ligands such as ... ...

Abstract	Allergen-specific sublingual immunotherapy (SLIT) is a potentially effective disease-modification treatment for patients with allergic asthma. Because CD44 signaling enhances regulatory T (Treg) cell-induction, administering CD44 ligands such as hyaluronan (HA) with allergen-specific SLIT may enhance the therapeutic effects. We evaluated the role of CD44 in Treg cell-induction in T helper type 2 (Th2)-mediated chronic airway inflammation using CD44-/- mice and the efficacy of HA on SLIT in a Dermatophagoides farinae (Df)-induced murine model of chronic asthma. Th2 responses and Treg cell induction were evaluated in CD44-/- mice. We devised a new SLIT model of Df-induced chronic asthma utilizing HA as an adjuvant. The effects of HA added to the new SLIT model were evaluated by the early asthmatic response (EAR) and airway hyperresponsiveness (AHR), eosinophilic airway inflammation, and serum Df-specific IgE levels. Th2-mediated chronic eosinophilic airway inflammation was worse in CD44-/- mice compared with Df-sensitized wild-type (WT) mice. HA enhanced the effect of Df-induced Treg cells in a CD44-dependent manner. Sublingual Df treatment in combination with HA, but not alone, normalized EAR and AHR, and significantly reduced the serum IgE levels and the bronchoalveolar lavage fluid (BALF) eosinophil number. HA also induced Treg cells in a Df-sensitized spleen cell culture in a CD44-dependent manner. The treatment-enhancing effects of HA in this SLIT model were diminished in CD44-/- mice. CD44 is a key contributor to Treg cell induction and critical for the enhancing effects of HA in a Df-induced murine model of chronic asthma.
MeSH term(s)	Allergens ; Animals ; Asthma/therapy ; Bronchoalveolar Lavage Fluid ; Disease Models, Animal ; Humans ; Hyaluronan Receptors ; Hyaluronic Acid ; Immunoglobulin E ; Inflammation ; Mice ; Mice, Inbred BALB C ; Mice, Knockout ; Sublingual Immunotherapy
Chemical Substances	Allergens ; Cd44 protein, mouse ; Hyaluronan Receptors ; Immunoglobulin E (37341-29-0) ; Hyaluronic Acid (9004-61-9)
Language	English
Publishing date	2022-04-28
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218531-3
ISSN	1365-2249 ; 0009-9104 ; 0964-2536
ISSN (online)	1365-2249
ISSN	0009-9104 ; 0964-2536
DOI	10.1093/cei/uxac024
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Zs.B 337: Show issues

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Article ; Online: A Single RET Mutation in Hirschsprung Disease Induces Intestinal Aganglionosis Via a Dominant-Negative Mechanism.

Sunardi, Mukhamad / Ito, Keisuke / Sato, Yuya / Uesaka, Toshihiro / Iwasaki, Mitsuhiro / Enomoto, Hideki

Cellular and molecular gastroenterology and hepatology

2022 Volume 15, Issue 6, Page(s) 1505–1524

Abstract: Background & aims: Hirschsprung disease (HSCR) is a congenital disorder characterized by the absence of the enteric nervous system (ENS). HSCR potentially involves multiple gene aberrations and displays complex patterns of inheritance. Mutations of the ... ...

Abstract	Background & aims: Hirschsprung disease (HSCR) is a congenital disorder characterized by the absence of the enteric nervous system (ENS). HSCR potentially involves multiple gene aberrations and displays complex patterns of inheritance. Mutations of the RET gene, encoding the RET receptor tyrosine kinase, play a central role in the pathogenesis of HSCR. Although a wide variety of coding RET mutations have been identified, their pathogenetic significance in vivo has remained largely unclear. Methods: We introduced a HSCR-associated RET missense mutation, RET(S811F), into the corresponding region (S812) of the mouse Ret gene. Pathogenetic impact of Ret(S812F) was assessed by histologic and functional analyses of the ENS and by biochemical analyses. Interactions of the Ret(S812F) allele with HSCR susceptibility genes, the RET9 allele and the Ednrb gene, were examined by genetic crossing in mice. Results: Ret Conclusions: This study demonstrates that a single RET missense mutation alone induces intestinal aganglionosis via a dominant-negative mechanism. The Ret
MeSH term(s)	Animals ; Mice ; Hirschsprung Disease/genetics ; Proto-Oncogene Proteins c-ret/genetics ; Proto-Oncogene Proteins c-ret/metabolism ; Mutation/genetics ; Neurons/metabolism ; Enteric Nervous System/metabolism
Chemical Substances	Proto-Oncogene Proteins c-ret (EC 2.7.10.1)
Language	English
Publishing date	2022-12-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2819778-1
ISSN	2352-345X ; 2352-345X
ISSN (online)	2352-345X
ISSN	2352-345X
DOI	10.1016/j.jcmgh.2022.12.003
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Article ; Online: Proton Hyperpolarization Relay from Nanocrystals to Liquid Water.

Matsumoto, Naoto / Nishimura, Koki / Kimizuka, Nobuo / Nishiyama, Yusuke / Tateishi, Kenichiro / Uesaka, Tomohiro / Yanai, Nobuhiro

Journal of the American Chemical Society

2022 Volume 144, Issue 39, Page(s) 18023–18029

Abstract: Dynamic nuclear polarization (DNP) using transient electron spin polarization generated by photoexcitation can improve nuclear magnetic resonance (NMR) sensitivity far beyond the thermal equilibrium limit for analysis in life science and drug discovery. ... ...

Abstract	Dynamic nuclear polarization (DNP) using transient electron spin polarization generated by photoexcitation can improve nuclear magnetic resonance (NMR) sensitivity far beyond the thermal equilibrium limit for analysis in life science and drug discovery. However, DNP of liquid water at room temperature remains an important challenge. Here, we propose a new method called hyperpolarization relay, in which the nonequilibrium polarization of electron spins is transferred to proton spins in the nanocrystals and then to proton spins in bulk water. Molecular nanocrystals doped with a polarizing agent that generates a highly polarized photoexcited triplet are synthesized by a reprecipitation method while controlling the size of the nanocrystals. The triplet-DNP sequence of repeated laser and microwave irradiation enhances the NMR signal of bulk water as well as nanocrystals. The smaller size of the nanocrystals increases the efficiency of polarization transfer from the nanocrystals to water due to the increased surface area. A series of control experiments and simulations based on Solomon equations confirmed the hyperpolarization relay mechanism.
MeSH term(s)	Magnetic Resonance Spectroscopy/methods ; Microwaves ; Nanoparticles ; Protons ; Water
Chemical Substances	Protons ; Water (059QF0KO0R)
Language	English
Publishing date	2022-09-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3155-0
ISSN	1520-5126 ; 0002-7863
ISSN (online)	1520-5126
ISSN	0002-7863
DOI	10.1021/jacs.2c07518
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Z 7.3: Show issues

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Article ; Online: Uts2b is a microbiota-regulated gene expressed in vagal afferent neurons connected to enteroendocrine cells producing cholecystokinin.

Yoshioka, Yuta / Tachibana, Yoshihisa / Uesaka, Toshihiro / Hioki, Hiroyuki / Sato, Yuya / Fukumoto, Takumi / Enomoto, Hideki

Biochemical and biophysical research communications

2022 Volume 608, Page(s) 66–72

Abstract: Enteroendocrine cells (EECs) are the primary sensory cells that sense the gut luminal environment and secret hormones to regulate organ function. Recent studies revealed that vagal afferent neurons are connected to EECs and relay sensory information from ...

Abstract	Enteroendocrine cells (EECs) are the primary sensory cells that sense the gut luminal environment and secret hormones to regulate organ function. Recent studies revealed that vagal afferent neurons are connected to EECs and relay sensory information from EECs to the brain stem. To date, however, the identity of vagal afferent neurons connected to a given EEC subtype and the mode of their gene responses to its intestinal hormone have remained unknown. Hypothesizing that EEC-associated vagal afferent neurons change their gene expression in response to the microbiota-related extracellular stimuli, we conducted comparative gene expression analyses of the nodose-petrosal ganglion complex (NPG) using specific pathogen-free (SPF) and germ-free (GF) mice. We report here that the Uts2b gene, which encodes a functionally unknown neuropeptide, urotensin 2B (UTS2B), is expressed in a microbiota-dependent manner in NPG neurons. In cultured NPG neurons, expression of Uts2b was induced by AR420626, the selective agonist for FFAR3. Moreover, distinct gastrointestinal hormones exerted differential effects on Uts2b expression in NPG neurons, where cholecystokinin (CCK) significantly increased its expression. The majority of Uts2b-expressing NPG neurons expressed CCK-A, the receptor for CCK, which comprised approximately 25% of all CCK-A-expressing NPG neurons. Selective fluorescent labeling of Uts2b-expressing NPG neurons revealed a direct contact of their nerve fibers to CCK-expressing EECs. This study identifies the Uts2b as a microbiota-regulated gene, demonstrates that Uts2b-expressing vagal afferent neurons transduce sensory information from CCK-expressing EECs to the brain, and suggests potential involvement of UTS2B in a modality of CCK actions.
MeSH term(s)	Animals ; Cholecystokinin/genetics ; Cholecystokinin/metabolism ; Enteroendocrine Cells/metabolism ; Intracellular Signaling Peptides and Proteins/genetics ; Intracellular Signaling Peptides and Proteins/metabolism ; Mice ; Microbiota ; Neurons, Afferent/metabolism ; Nodose Ganglion/metabolism ; Peptide Hormones/genetics ; Peptide Hormones/metabolism ; Vagus Nerve/metabolism
Chemical Substances	Intracellular Signaling Peptides and Proteins ; Peptide Hormones ; Uts2b protein, mouse ; Cholecystokinin (9011-97-6)
Language	English
Publishing date	2022-03-31
Publishing country	United States
Document type	Journal Article
ZDB-ID	205723-2
ISSN	1090-2104 ; 0006-291X ; 0006-291X
ISSN (online)	1090-2104 ; 0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2022.03.117
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Zs.A 116: Show issues

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