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Article: [A novel ligand for chemogenetic receptors, Deschloroclozapine, enables rapid and selective modulation of neuronal activity and behavior in living animals].

Nagai, Yuji

Nihon yakurigaku zasshi. Folia pharmacologica Japonica

2022 Volume 157, Issue 4, Page(s) 233–237

Abstract: A brain function is manifested by harmonizing some brain regions responsible for the function. Since pathological conditions in neuropsychiatric disorders are induced by the failure of this mechanism, it is crucial to identify the affected function by ... ...

Abstract	A brain function is manifested by harmonizing some brain regions responsible for the function. Since pathological conditions in neuropsychiatric disorders are induced by the failure of this mechanism, it is crucial to identify the affected function by manipulating the specific brain regions. Designer receptors exclusively activated by designer drugs (DREADDs) are one of the chemogenetic tools that offer a means to repeatedly reversible control of the activity of a target neural population expressing a "designer receptor" by systemic injection of "designer drug," which is biologically inert. The most widely used DREADDs are muscarinic-based receptors, such as hM3Dq (excitatory) and hM4Di (inhibitory), which can be activated by clozapine-N-oxide (CNO). However, CNO has some concerns. First, because CNO has a modest brain penetrability, the effect is slow. Second, since CNO is metabolized to clozapine, an antipsychotic drug that acts on numerous endogenous receptors, the systemic administration may produce off-target actions. Therefore, we developed a new compound, deschloroclozapine (DCZ), to solve these issues. DCZ has a higher affinity and greater agonist potency than CNO with reduced off-target actions and can rapidly modulate the neuronal activity and behavior with muscarinic-based DREADDs in living animals. Given the potential weak point of CNO, DCZ affords clear benefits to many users of muscarinic-based DREADD, with increased reliability by removing concerns about possible off-target responses.
MeSH term(s)	Animals ; Cholinergic Agents/metabolism ; Cholinergic Agents/pharmacology ; Clozapine/metabolism ; Clozapine/pharmacology ; Ligands ; Neurons ; Reproducibility of Results
Chemical Substances	Cholinergic Agents ; Ligands ; Clozapine (J60AR2IKIC)
Language	Japanese
Publishing date	2022-03-01
Publishing country	Japan
Document type	Journal Article
ZDB-ID	1097532-9
ISSN	1347-8397 ; 0015-5691
ISSN (online)	1347-8397
ISSN	0015-5691
DOI	10.1254/fpj.22012
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Article ; Online: Production scheme for diagnostic-therapeutic radioisotopes by accelerator neutrons.

Nagai, Yasuki

Proceedings of the Japan Academy. Series B, Physical and biological sciences

2021 Volume 97, Issue 6, Page(s) 292–323

Abstract: Interest has been growing in the development of medical radioisotopes used for noninvasive nuclear medicine imaging of disease and cancer therapy. Especially the development of an alternative production scheme ... ...

Abstract	Interest has been growing in the development of medical radioisotopes used for noninvasive nuclear medicine imaging of disease and cancer therapy. Especially the development of an alternative production scheme of
MeSH term(s)	Molybdenum ; Neutrons ; Radioisotopes ; Radiopharmaceuticals ; Technetium
Chemical Substances	Radioisotopes ; Radiopharmaceuticals ; Technetium (7440-26-8) ; Molybdenum (81AH48963U)
Language	English
Publishing date	2021-06-11
Publishing country	Japan
Document type	Journal Article
ZDB-ID	161781-3
ISSN	1349-2896 ; 0386-2208
ISSN (online)	1349-2896
ISSN	0386-2208
DOI	10.2183/pjab.97.017
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Article: The Promise of Retinoids in the Treatment of Cancer: Neither Burnt Out Nor Fading Away.

Nagai, Yuya / Ambinder, Alexander J

Cancers

2023 Volume 15, Issue 14

Abstract: Since the introduction of all-trans retinoic acid (ATRA), acute promyelocytic leukemia (APL) has become a highly curable malignancy, especially in combination with arsenic trioxide (ATO). ATRA's success has deepened our understanding of the role of the ... ...

Abstract	Since the introduction of all-trans retinoic acid (ATRA), acute promyelocytic leukemia (APL) has become a highly curable malignancy, especially in combination with arsenic trioxide (ATO). ATRA's success has deepened our understanding of the role of the RARα pathway in normal hematopoiesis and leukemogenesis, and it has influenced a generation of cancer drug development. Retinoids have also demonstrated some efficacy in a handful of other disease entities, including as a maintenance therapy for neuroblastoma and in the treatment of cutaneous T-cell lymphomas; nevertheless, the promise of retinoids as a differentiating therapy in acute myeloid leukemia (AML) more broadly, and as a cancer preventative, have largely gone unfulfilled. Recent research into the mechanisms of ATRA resistance and the biomarkers of RARα pathway dysregulation in AML have reinvigorated efforts to successfully deploy retinoid therapy in a broader subset of myeloid malignancies. Recent studies have demonstrated that the bone marrow environment is highly protected from exogenous ATRA via local homeostasis controlled by stromal cells expressing CYP26, a key enzyme responsible for ATRA inactivation. Synthetic CYP26-resistant retinoids such as tamibarotene bypass this stromal protection and have shown superior anti-leukemic effects. Furthermore, recent super-enhancer (SE) analysis has identified a novel AML subgroup characterized by high expression of RARα through strong SE levels in the gene locus and increased sensitivity to tamibarotene. Combined with a hypomethylating agent, synthetic retinoids have shown synergistic anti-leukemic effects in non-APL AML preclinical models and are now being studied in phase II and III clinical trials.
Language	English
Publishing date	2023-07-08
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15143535
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Article ; Online: Autonomic biofeedback therapy in epilepsy.

Nagai, Yoko

Epilepsy research

2019 Volume 153, Page(s) 76–78

Abstract: Pharmacological intervention is a mainstay for treatment of epilepsy. However, a third of patients with epilepsy remain drug resistant. Behavioural treatments such as biofeedback training can be potential effective alternative interventions for drug ... ...

Abstract	Pharmacological intervention is a mainstay for treatment of epilepsy. However, a third of patients with epilepsy remain drug resistant. Behavioural treatments such as biofeedback training can be potential effective alternative interventions for drug resistant epilepsy. This paper describes a biofeedback therapy in which the training of patients to control peripheral autonomic tone (galvanic skin response) changes in central control of seizure occurrence. This paper introduces; 1) the theoretical development of methodology, 2) the effect of GSR biofeedback in reducing seizure frequency in drug resistant epilepsy, 3) insights into the neural mechanisms of effective GSR biofeedback through neuromodulatory autonomic control and 3) future prospects of this approach as a therapeutic tool instantiated as an Autonomic Cognitive Rehabituation Training (ACRT).
MeSH term(s)	Autonomic Nervous System/physiology ; Biofeedback, Psychology/methods ; Double-Blind Method ; Epilepsy/therapy ; Galvanic Skin Response/physiology ; Humans ; Randomized Controlled Trials as Topic
Language	English
Publishing date	2019-02-20
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	632939-1
ISSN	1872-6844 ; 0920-1211
ISSN (online)	1872-6844
ISSN	0920-1211
DOI	10.1016/j.eplepsyres.2019.02.005
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Article: A General Framework for Tilings, Delone Sets, Functions, and Measures and Their Interrelation.

Nagai, Yasushi

Discrete & computational geometry

2019 Volume 62, Issue 2, Page(s) 241–291

Abstract: We define a general framework that includes objects such as tilings, Delone sets, functions, and measures. We define local derivability and mutual local derivability (MLD) between any two of these objects in order to describe their interrelation. This is ...

Abstract	We define a general framework that includes objects such as tilings, Delone sets, functions, and measures. We define local derivability and mutual local derivability (MLD) between any two of these objects in order to describe their interrelation. This is a generalization of the local derivability and MLD (or S-MLD) for tilings and Delone sets which are used in literature, under a mild assumption. We show that several canonical maps in aperiodic order send an object
Language	English
Publishing date	2019-07-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	2187235-1
ISSN	0179-5376 ; 0179-5376
ISSN (online)	0179-5376
ISSN	0179-5376
DOI	10.1007/s00454-019-00081-2
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Article ; Online: Effect of information provision by familial nudging on attitudes toward offshore wind power.

Komatsu, Hidenori / Kubota, Hiromi / Asano, Kenji / Nagai, Yu

PloS one

2024 Volume 19, Issue 1, Page(s) e0297199

Abstract: Offshore wind power (OWP) is a promising way to achieve decarbonization and tackle global climate change, but acceptance by residents is an important issue for site location. Information provision could be a more cost-effective intervention than debates ... ...

Abstract	Offshore wind power (OWP) is a promising way to achieve decarbonization and tackle global climate change, but acceptance by residents is an important issue for site location. Information provision could be a more cost-effective intervention than debates or subsidies, assuming that scientifically correct information alone is insufficient and information design to boost the message effects considering realistic human responses is necessary. Thus, we designed nudging messages to increase acceptance of OWP, using a message framework to moderate risk-averse attitudes by reminding readers of familial support based on insights from kin selection theory from evolutionary psychology. A randomized controlled trial based on an internet survey of more than 4000 responses from the general public was performed to investigate the message effects. The messages significantly moderated the risk-averse attitudes toward OWP by 0.228 on average on a five-point Likert scale, which meant that about 5 people out of 100 changed their attitudes to be safer by 1 point. This suggests that disseminating flyers using nudging messages might be an effective way to increase acceptance. We also extracted responses from those who mentioned fisheries in an open-ended question as an alternative to actual fishers. Responses from this segment were more complex and the message effects were limited compared with those who did not mention fisheries; although the attitudes toward OWP before receiving the messages were safer, reading descriptions for potential risks on fisheries may have unexpectedly led them to focus on the risks of which they were unaware at first. Because information provision based on nudging is effective but just one of a wide variety of political interventions available, practitioners should consider a combination of multiple options instead of using only nudging messages.
MeSH term(s)	Humans ; Wind ; Attitude
Language	English
Publishing date	2024-01-17
Publishing country	United States
Document type	Randomized Controlled Trial ; Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0297199
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Article ; Online: Predictive learning: its key role in early cognitive development.

Nagai, Yukie

Philosophical transactions of the Royal Society of London. Series B, Biological sciences

2019 Volume 374, Issue 1771, Page(s) 20180030

Abstract: What is a fundamental ability for cognitive development? Although many researchers have been addressing this question, no shared understanding has been acquired yet. We propose that predictive learning of sensorimotor signals plays a key role in early ... ...

Abstract	What is a fundamental ability for cognitive development? Although many researchers have been addressing this question, no shared understanding has been acquired yet. We propose that predictive learning of sensorimotor signals plays a key role in early cognitive development. The human brain is known to represent sensorimotor signals in a predictive manner, i.e. it attempts to minimize prediction error between incoming sensory signals and top-down prediction. We extend this view and suggest that two mechanisms for minimizing prediction error lead to the development of cognitive abilities during early infancy. The first mechanism is to update an immature predictor. The predictor must be trained through sensorimotor experiences because it does not inherently have prediction ability. The second mechanism is to execute an action anticipated by the predictor. Interacting with other individuals often increases prediction error, which can be minimized by executing one's own action corresponding to others' action. Our experiments using robotic systems replicated developmental dynamics observed in infants. The capabilities of self-other cognition and goal-directed action were acquired based on the first mechanism, whereas imitation and prosocial behaviours emerged based on the second mechanism. Our theory further provides a potential mechanism for autism spectrum condition. Atypical tolerance for prediction error is hypothesized to be a cause of perceptual and social difficulties. This article is part of the theme issue 'From social brains to social robots: applying neurocognitive insights to human-robot interaction'.
MeSH term(s)	Autism Spectrum Disorder/psychology ; Brain/physiology ; Cognition ; Humans ; Infant ; Learning ; Robotics
Language	English
Publishing date	2019-03-21
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	208382-6
ISSN	1471-2970 ; 0080-4622 ; 0264-3839 ; 0962-8436
ISSN (online)	1471-2970
ISSN	0080-4622 ; 0264-3839 ; 0962-8436
DOI	10.1098/rstb.2018.0030
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Article: Differences in cough strength, respiratory function, and physical performance in older adults with and without low swallowing function in the repetitive saliva swallowing test.

Kaneko, Hideo / Suzuki, Akari / Nagai, Yoshiharu / Horie, Jun

Journal of physical therapy science

2024 Volume 36, Issue 5, Page(s) 273–277

Abstract: Purpose] In older adults, the risk of aspiration pneumonia increases because of coexisting factors such as age-related decline in swallowing function, inefficient cough, reduced respiratory function, and poor physical performance. This study aimed to ... ...

Abstract	[Purpose] In older adults, the risk of aspiration pneumonia increases because of coexisting factors such as age-related decline in swallowing function, inefficient cough, reduced respiratory function, and poor physical performance. This study aimed to investigate the differences in cough strength, respiratory function, and physical performance in community-dwelling ambulatory older adults with and without low swallowing function. [Participants and Methods] In 225 community-dwelling ambulatory older adults, swallowing function (the repetitive saliva swallowing test, RSST), cough strength (peak cough flow), lung function (forced vital capacity, forced expiratory volume in 1 second/forced vital capacity), respiratory muscle strength (maximum inspiratory and expiratory pressures), and physical performance (30-second chair stand test and Timed Up and Go test) were evaluated. Participants with low swallowing function in RSST (low RSST group) were compared to age- and sex-matched participants without low swallowing function (control group). [Results] Peak cough flow and maximum inspiratory and expiratory pressures were significantly lower in the low RSST group (n=14) than the control group (n=14). [Conclusion] These preliminary results suggest that community-dwelling ambulatory older adults with low swallowing function in RSST might have lower cough and respiratory muscle strength, even if they have relatively preserved lung function and physical performance.
Language	English
Publishing date	2024-05-01
Publishing country	Japan
Document type	Journal Article
ZDB-ID	2038898-6
ISSN	0915-5287
ISSN	0915-5287
DOI	10.1589/jpts.36.273
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Article ; Online: Prediction of the photoelectrochemical performance of hematite electrodes using analytical data.

Nagai, Yuya / Katayama, Kenji

The Analyst

2022 Volume 147, Issue 7, Page(s) 1313–1320

Abstract: Machine learning (ML) has been extensively utilized in various fields of chemistry, such as molecular design and optimization of the fabrication parameters of the material. However, there is still a difficulty in applying ML for devices/materials ... ...

Abstract	Machine learning (ML) has been extensively utilized in various fields of chemistry, such as molecular design and optimization of the fabrication parameters of the material. However, there is still a difficulty in applying ML for devices/materials fabricated in a lab because plenty of data for accurate calculation are difficult to obtain due to the limited number of samples. As a promising energy-harvesting material, we have studied hematite electrodes for photocatalytic water splitting. Herein, we have examined the critical factors affecting the photoelectrochemical (PEC) performance by applying ML for a limited number of fabricated electrodes to reveal the origin of poor reproducibility of the performance. To find the dominant factors affecting the PEC performance, the feature values were directly extracted from analytical data such as X-ray diffraction, Raman, UV/vis and photoelectrochemical impedance spectroscopy (PEIS) measurements. The dominant factors for the performance were identified from the prediction analysis of the performance by ML. Two types of descriptors were examined; all the analytical data were included and those without the PEIS data, which had a high correlation with the photocurrent. The determination coefficients (
Language	English
Publishing date	2022-03-28
Publishing country	England
Document type	Journal Article
ZDB-ID	210747-8
ISSN	1364-5528 ; 0003-2654
ISSN (online)	1364-5528
ISSN	0003-2654
DOI	10.1039/d2an00227b
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Article ; Online: The molecular pathogenesis of repeat expansion diseases.

Fujino, Yuzo / Nagai, Yoshitaka

Biochemical Society transactions

2022 Volume 50, Issue 1, Page(s) 119–134

Abstract: Expanded short tandem repeats in the genome cause various monogenic diseases, particularly neurological disorders. Since the discovery of a CGG repeat expansion in the FMR1 gene in 1991, more than 40 repeat expansion diseases have been identified to date. ...

Abstract	Expanded short tandem repeats in the genome cause various monogenic diseases, particularly neurological disorders. Since the discovery of a CGG repeat expansion in the FMR1 gene in 1991, more than 40 repeat expansion diseases have been identified to date. In the coding repeat expansion diseases, in which the expanded repeat sequence is located in the coding regions of genes, the toxicity of repeat polypeptides, particularly misfolding and aggregation of proteins containing an expanded polyglutamine tract, have been the focus of investigation. On the other hand, in the non-coding repeat expansion diseases, in which the expanded repeat sequence is located in introns or untranslated regions, the toxicity of repeat RNAs has been the focus of investigation. Recently, these repeat RNAs were demonstrated to be translated into repeat polypeptides by the novel mechanism of repeat-associated non-AUG translation, which has extended the research direction of the pathological mechanisms of this disease entity to include polypeptide toxicity. Thus, a common pathogenesis has been suggested for both coding and non-coding repeat expansion diseases. In this review, we briefly outline the major pathogenic mechanisms of repeat expansion diseases, including a loss-of-function mechanism caused by repeat expansion, repeat RNA toxicity caused by RNA foci formation and protein sequestration, and toxicity by repeat polypeptides. We also discuss perturbation of the physiological liquid-liquid phase separation state caused by these repeat RNAs and repeat polypeptides, as well as potential therapeutic approaches against repeat expansion diseases.
MeSH term(s)	Fragile X Mental Retardation Protein/genetics ; Humans ; Nervous System Diseases ; Peptides/genetics ; RNA/genetics ; Trinucleotide Repeat Expansion/genetics ; Untranslated Regions
Chemical Substances	FMR1 protein, human ; Peptides ; Untranslated Regions ; Fragile X Mental Retardation Protein (139135-51-6) ; RNA (63231-63-0)
Language	English
Publishing date	2022-01-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	184237-7
ISSN	1470-8752 ; 0300-5127
ISSN (online)	1470-8752
ISSN	0300-5127
DOI	10.1042/BST20200143
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