Publications by authors named "Manabu Abe"

Photochemical transformations of glycosyl bromides are investigated in the presence of amines. The choice of amines such as N,N-diisopropylethylamine and triphenylamine was found to be critical for product selectivity. Alkylation and alkenylation of anomeric carbon with 1,1-diphenylethene could be realized.

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Photoenols, formed through photoinduced intramolecular H atom abstraction in -alkyl-substituted arylketones, typically have limited utility as reactive intermediates owing to fast reversion to the starting material. Herein, we introduced an azido group on the -alkyl substituent to render the photoreaction irreversible. Irradiation of 2-azidomethylbenzophenone () in methanol yielded 2-(hydroxy(phenyl)methyl)benzonitrile ().

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Resiquimod, an imidazoquinoline scaffold, exhibits potent immunotherapeutic activity but is associated with off-target effects, limiting its clinical utility. To address this limitation, we developed a novel BODIPY-caged resiquimod that is responsive to red light, combining photocaging and photodynamic therapy functionalities. Molecular docking studies guided identification of the optimal caging site for resiquimod, effectively masking its immune activity.

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AUTS2 syndrome is characterized by intellectual disability and microcephaly, and is often associated with autism spectrum disorder, but the underlying mechanisms, particularly concerning microcephaly, remain incompletely understood. Here, we analyze mice mutated for the transcriptional regulator AUTS2, which recapitulate microcephaly. Their brains exhibit reduced division of intermediate progenitor cells (IPCs), leading to fewer neurons and decreased thickness in the upper-layer cortex.

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The formation of new social interactions is vital for social animals, but the underlying neural mechanisms remain poorly understood. We identified CeA neurons, a population in central amygdala expressing neuropeptide B/W receptor-1 (NPBWR1), that play a critical role in these interactions. CeA neurons were activated during encounters with unfamiliar, but not with familiar, mice.

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Although nitrene chemistry is promising for the light-induced modification of organic compounds, the reactivity of large polycyclic aromatic compounds and the effects of their curvature remain unexplored. Irradiation of azidocorannulene () in methanol/acetonitrile followed by HCl addition produced diastereomers and . Azirine is apparently trapped by methanol to form diastereomeric acetal derivatives that are hydrolyzed with HCl to yield and '.

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Radical coupling reactions are generally known to have a low selectivity due to the high reactivity of radicals. In this study, high regio and substrate selectivity was discovered in the dimerization of triarylimidazolyl radicals (), a versatile photochromic reaction. When two different radicals, 2-(4-cyanophenyl)-4,5-diphenyl-1-imidazolyl radical () and 2-(4-methoxyphenyl)-4,5-diphenyl-1-imidazolyl radical (), were simultaneously generated in situ, a hexaarylbiimidazole, formed by selective coupling at the nitrogen atom at position 1 of and the carbon atom at position 2 of , was isolated with high selectivity as the main product among 24 possible radical dimer hexaarylbiimidazole derivatives.

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The design and synthesis of two-photon-responsive chromophores have recently garnered significant attention owing to their potential applications in materials and life sciences. In this study, a novel π-conjugated system, 2-dimethylaminophenyl-5-nitrophenylthiophene derivatives, featuring a thiophene unit as the π-linker between the donor (NMeCH-) and acceptor (NOCH-) units was designed, synthesized, and applied for the development of two-photon-responsive chromophores as a photoremovable protecting group in the near-infrared region. Notably, the positional effect of the nitro group (NO), meta versus para position, was observed in the uncaging process of benzoic acid.

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The idea of utilizing unused oocytes present in the ovaries has been tested in various ways to produce offspring. However, only a limited number of studies succeeded in offspring generation. They include transplantation of ovaries into autologous or allogeneic animals, and acquisition of pups from oocytes obtained by transplanting mouse ovaries into immunodeficient rats.

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Metabolic dysfunction-associated steatohepatitis (MASH, previously termed non-alcoholic steatohepatitis (NASH)), is a major complication of obesity that promotes fatty liver disease. MASH is characterized by progressive tissue fibrosis and sterile liver inflammation that can lead to liver cirrhosis, cancer, and death. The molecular mechanisms of fibrosis in MASH and its systemic control remain poorly understood.

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Article Synopsis
  • The VPS13A gene encodes a lipid transfer protein critical for communication and lipid transport between organelles, impacting mitochondrial and endoplasmic reticulum functions.
  • Mutations in this gene are linked to chorea-acanthocytosis (ChAc), a neurodegenerative disorder that causes movement issues, seizures, and cognitive impairment.
  • The study created a specific knockout mouse model to explore ChAc and found that while these mice had increased reticulocytes and abnormal sperm production leading to male infertility, they did not show significant changes in brain inflammation markers.
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Photochemical multi-component coupling reactions initiated by the activation of glycosyl bromides in the presence of 1,4-bis(diphenylamino)benzene (BDB) as an organic photocatalyst were developed. -glycosides accompanied by olefin (di)functionalization were obtained. This method allows us to access various -glycosides with alkene, carbonyl, alcohol, ether, and amide functionalities.

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  • Developmental synapse elimination is essential for forming mature neural circuits, particularly in the cerebellum of neonatal mice where Purkinje cells initially connect with multiple climbing fibers.
  • By postnatal day 20, all climbing fiber synapses except one are eliminated, with heterosynaptic interactions between climbing fibers and parallel fibers playing a key role in this process.
  • The study finds that the deletion of AMPA receptors in granule cells disrupts the elimination of climbing fiber synapses, highlighting the importance of parallel fiber activity, which may enhance synapse elimination by activating mGlu1 receptors in Purkinje cells and NMDA receptors in molecular layer interneurons.
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Neuroinflammation has been gaining attention as one of the potential causes of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis in recent years. The suppression of excessive proinflammatory responses is expected to be a target for the treatment and prevention of neurodegenerative diseases. Collapsin response mediator protein 4 (CRMP4) is involved in cytoskeleton-associated axonal guidance in the developing brain.

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Article Synopsis
  • Accumulation of senescent cells leads to pathological aging, but removing these cells (senolysis) can improve age-related issues.
  • The SGLT2 inhibitor canagliflozin helps eliminate senescent cells in mice with dietary obesity, reducing inflammation and metabolic problems without relying on insulin treatment.
  • Canagliflozin not only extends lifespan in mice with premature aging but also enhances immune clearance of senescent cells by affecting specific metabolic pathways.
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The Norrish type I (α-cleavage) reaction is an excellent photochemical method for radical-pair formation in solution. However, in cryogenic matrices, the starting material typically re-forms before the radical pair diffuses apart. This study focused on N extrusion from an azido alkyl radical to prevent radical-pair recombination.

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Optochemistry, an emerging pharmacologic approach in which light is used to selectively activate or deactivate molecules, has the potential to alleviate symptoms, cure diseases, and improve quality of life while preventing uncontrolled drug effects. The development of in-vivo applications for optochemistry to render brain cells photoresponsive without relying on genetic engineering has been progressing slowly. The nucleus accumbens (NAc) is a region for the regulation of slow-wave sleep (SWS) through the integration of motivational stimuli.

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Golli-myelin basic proteins, encoded by the myelin basic protein gene, are widely expressed in neurons and oligodendrocytes in the central nervous system. Further, prior research has shown that Golli-myelin basic protein is necessary for myelination and neuronal maturation during central nervous system development. In this study, we established Golli-myelin basic protein-floxed mice to elucidate the cell-type-specific effects of Golli-myelin basic protein knockout through the generation of conditional knockout mice (Golli-myelin basic proteins; E3CreN), in which Golli-myelin basic proteins were specifically deleted in cerebellar granule neurons, where Golli-myelin basic proteins are expressed abundantly in wild-type mice.

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Single-molecule localization microscopy (SMLM) based on temporal-focusing multiphoton excitation (TFMPE) and single-wavelength excitation is used to visualize the three-dimensional (3D) distribution of spontaneously blinking fluorophore-labeled subcellular structures in a thick specimen with a nanoscale-level spatial resolution. To eliminate the photobleaching effect of unlocalized molecules in out-of-focus regions for improving the utilization rate of the photon budget in 3D SMLM imaging, SMLM with single-wavelength TFMPE achieves wide-field and axially confined two-photon excitation (TPE) of spontaneously blinking fluorophores. TPE spectral measurement of blinking fluorophores is then conducted through TFMPE imaging at a tunable excitation wavelength, yielding the optimal TPE wavelength for increasing the number of detected photons from a single blinking event during SMLM.

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Proper regulation of N-methyl-D-aspartate-type glutamate receptor (NMDA receptor) expression is responsible for excitatory synaptic functions in the mammalian brain. NMDA receptor dysfunction can cause various neuropsychiatric disorders and neurodegenerative diseases. Posttranslational protein S-palmitoylation, the covalent attachment of palmitic acid to intracellular cysteine residues via thioester bonds, occurs in the carboxyl terminus of GluN2B, which is the major regulatory NMDA receptor subunit.

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Photoreactions of (coumarin-4-yl)methyl derivatives have been extensively studied in many fields of chemistry, including organic synthesis and photoinduced drug delivery systems. The identification of the reaction intermediates involved in the photoreactions is crucial not only for elucidating the reaction mechanism but also for the application of the photoreactions. In this study, the photoreactions of 7-diethylamino(coumarin-4-yl)methyl thioester [-SC(O)CH], thionoester [-OC(S)CH], and ester [-OC(O)CH] were investigated to clarify the intermediary species and their chemical behavior.

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Photoremovable protecting groups (PPGs) are powerful tools that are widely used to investigate biological events in cells. An important requirement for PPGs is the efficient release of bioactive molecules by using visible to near-infrared light in the biological window (650-1350 nm). In this study, we report a new two-photon (2P)-responsive PPG, 2-(-aminophenyl)-5,6-dimethoxy-1-(hydroxyinden-3-yl)methyl, with a donor-π-donor cyclic stilbene structure.

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Kainate receptors (KARs) are one of the ionotropic glutamate receptors in the central nervous system (CNS) comprised of five subunits, GluK1-GluK5. There is a growing interest in the association between KARs and psychiatric disorders, and there have been several studies investigating the behavioral phenotypes of KAR deficient mice, however, the difference in the genetic background has been found to affect phenotype in multiple mouse models of human diseases. Here, we examined GluK1-5 single KO mice in a pure C57BL/6N background and identified that GluK3 KO mice specifically express anxiolytic-like behavior with an alteration in dopamine D2 receptor (D2R)-induced anxiety, and reduced D2R expression in the striatum.

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