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61.
Tomoyuki MIYAZAKI Hiroki ABE Hiroyuki UCHIDA Takuya TAKAHASHI 《Proceedings of the Japan Academy. Series B, Physical and biological sciences》2021,97(1):1
Psychiatric and neurological disorders severely hamper patient’s quality of life. Despite their high unmet needs, the development of diagnostics and therapeutics has only made slow progress. This is due to limited evidence on the biological basis of these disorders in humans. Synapses are essential structural units of neurotransmission, and neuropsychiatric disorders are considered as “synapse diseases”. Thus, a translational approach with synaptic physiology is crucial to tackle these disorders. Among a variety of synapses, excitatory glutamatergic synapses play central roles in neuronal functions. The glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) is a principal component of glutamatergic neurotransmission; therefore, it is considered to be a promising translational target. Here, we review the limitations of current diagnostics and therapeutics of neuropsychiatric disorders and advocate the urgent need for the promotion of translational medicine based on the synaptic physiology of AMPAR. Furthermore, we introduce our recent translational approach to these disorders by targeting at AMPARs. 相似文献
62.
Specific reactivity of 2,4,6-tri-tert-butylanilide anions and its application to benzylation reagent
The reaction of methyl iodide with an anilide anion prepared from 2,4,6-tri-tert-butylanilide and NaH in CH3CN gave N-methyl anilide (N-alkylation product) as a major product, while in the reaction of benzyl bromide with the anilide anion in DMF, O-benzyl imidate (O-alkylation product) was obtained with almost complete selectivity. The treatment of O-benzyl imidate with alcohols and carboxylic acids in the presence of trifluoromethane sulfonic acid gave benzyl ethers and benzyl esters, respectively. 相似文献
63.
Bis(trifluoromethanesulfonyl)amide (TFSA), hexafluorophosphate (PF(6)(-)), and iodide salts of 1-ferrocenyl-3-alkylimidazolium were prepared and their thermal and physical properties, including the dependence on alkyl chain length (methyl-hexadecyl), were investigated. The TFSA salts were highly viscous ionic liquids with melting points around room temperature. 1-Ferrocenyl-4-methyltriazolium salts were also prepared for comparison. The ferrocenylimidazolium and ferrocenyltriazolium cations showed redox waves for both the ferrocenyl moiety and the azolium moiety and exhibited corresponding charge-transfer bands at around 330 nm, which were analyzed using the Marcus-Hush model. Crystal structure determinations at low temperature revealed that the PF(6) and iodide salts form layerlike structures composed of ionic layers of the charged moieties. The TFSA salt exhibited short hydrogen-bond-like intermolecular contacts between the hydrogen atoms of the cation and oxygen atoms of the anion. 相似文献
64.
Satoshi Motodate Takuya Kobayashi Mikio Fujii Prof. Tomoyuki Mochida Dr. Taichi Kusakabe Shigeki Katoh Prof. Hiroyuki Akita Prof. Keisuke Kato 《化学:亚洲杂志》2010,5(10):2221-2230
Bis(oxazoline)‐palladium(II) catalyzed carbonylation of homopropargyl alcohols afforded acyclic methoxyacrylate 2 and 6‐membered lactone 3a , 3b , 3d , 3e , 3f , 3g , 3h , 3i , 3j , 3k in good combined yield. In the case of propargyl alcohols, 5‐membered lactones 3p , 3q , 16 were obtained in moderate yields. The one‐pot synthesis of kawa lactones 3a , 3r , 3s and formal synthesis of dihydroxycystothiazole A and dihydroxycystothiazole C are presented. To elucidate the stereochemistry of (+)‐annularin G and (?)‐annularin H, the first asymmetric syntheses of these natural products were achieved. 相似文献
65.
66.
67.
Fumihiko Maekawa Okiru Komine Katsushige Sato Tomoyuki Kanamatsu Motoaki Uchimura Kohichi Tanaka Hiroko Ohki-Hamazaki 《BMC neuroscience》2006,7(1):1-13
Background
Results of the Women's Health Initiative Memory Study (WHIMS) raised concerns regarding the timing and formulation of hormone interventions. Conjugated equine estrogens (CEE), used as the estrogen therapy in the WHIMS trial, is a complex formulation containing multiple estrogens, including several not secreted by human ovaries, as well as other biologically active steroids. Although the full spectrum of estrogenic components present in CEE has not yet been resolved, 10 estrogens have been identified. In the present study, we sought to determine which estrogenic components, at concentrations commensurate with their plasma levels achieved following a single oral dose of 0.625 mg CEE (the dose used in the WHIMS trial) in women, are neuroprotective and whether combinations of those neuroprotective estrogens provide added benefit. Further, we sought, through computer-aided modeling analyses, to investigate the potential correlation of the molecular mechanisms that conferred estrogen neuroprotection with estrogen interactions with the estrogen receptor (ER).Results
Cultured basal forebrain neurons were exposed to either β-amyloid25–35 or excitotoxic glutamate with or without pretreatment with estrogens followed by neuroprotection analyses. Three indicators of neuroprotection that rely on different aspects of neuronal damage and viability, LDH release, intracellular ATP level and MTT formazan formation, were used to assess neuroprotective efficacy. Results of these analyses indicate that the estrogens, 17α-estradiol, 17β-estradiol, equilin, 17α-dihydroequilin, equilinen, 17α-dihydroequilenin, 17β-dihydroequilenin, and Δ8,9-dehydroestrone were each significantly neuroprotective in reducing neuronal plasma membrane damage induced by glutamate excitotoxicity. Of these estrogens, 17β-estradiol and Δ8,9-dehydroestrone were effective in protecting neurons against β-amyloid25–35-induced intracellular ATP decline. Coadministration of two out of three neuroprotective estrogens, 17β-estradiol, equilin and Δ8,9-dehydroestrone, exerted greater neuroprotective efficacy than individual estrogens. Computer-aided analyses to determine structure/function relationships between the estrogenic structures and their neuroprotective activity revealed that the predicted intermolecular interactions of estrogen analogues with ER correlate to their overall neuroprotective efficacy.Conclusion
The present study provides the first documentation of the neuroprotective profile of individual estrogens contained within the complex formulation of CEE at concentrations commensurate with their plasma levels achieved after an oral administration of 0.625 mg CEE in women. Our analyses demonstrate that select estrogens within the complex formulation of CEE contribute to its neuroprotective efficacy. Moreover, our data predict that the magnitude of neuroprotection induced by individual estrogens at relatively low concentrations may be clinically undetectable and ineffective, whereas, a combination of select neuroprotective estrogens could provide an increased and clinically meaningful efficacy. More importantly, these data suggest a strategy for determining neurological efficacy and rational design and development of a composition of estrogen therapy to alleviate climacteric symptoms, promote neurological health, and prevent age-related neurodegeneration, such as AD, in postmenopausal women. 相似文献68.
Tomoyuki Suzuki 《Algebra Universalis》2011,66(3):243-276
In this paper, we discuss the canonical extension of poset expansions. To obtain canonicity results on poset expansions, we
study Ghilardi and Meloni’s canonicity methodology for Heyting algebras with unary modalities, raise the problem of extending
the technique to poset expansions, and give a possible solution for the problem. Finally, we obtain a syntactic account of
canonical inequalities on poset expansions consisting of constants, e^{\epsilon_{\bot}} -additive operations, eT{\epsilon^{\top}} -multiplicative operations, diamond, box, and strict adjoint pairs, and bounded poset expansions consisting of constants,
e{\epsilon} -join preserving operations, e{\epsilon} -meet preserving operations, e{\epsilon} -additive operations, e{\epsilon} -multiplicative operations and adjoint pairs, which are more restricted than the case of lattice expansions, but can still
account for Sahlqvist-like canonicity results. 相似文献
69.
The reaction of zirconium n-propoxide in glycol at 300°C yielded microcrystalline tetragonal zirconia (ZrO2). The crystallite size of the product depended on the carbon number of the glycol and increased in the following order (carbon
number of glycol): 2<6<4, which suggested that the heterolytic cleavage of O-C bond of gylcoxide formed by transesterification
is the prime factor for the formation of the product. In toluene, zirconium isopropoxide also gave tetragonal zirconia at
300°C, and zirconium tert-butoxide decomposed at 200°C yielding amorphous zirconia, while zirconium n-propoxide was stable at 300°C. These results suggest that the reaction in toluene depends on the structure of the alkyl group
of the alkoxides. Thus-obtained tetragonal zirconias maintained large surface areas (90–160 m2/g) even after calcination at 500°C. 相似文献
70.
This paper presents objective priors for robust Bayesian estimation against outliers based on divergences. The minimum -divergence estimator is well-known to work well in estimation against heavy contamination. The robust Bayesian methods by using quasi-posterior distributions based on divergences have been also proposed in recent years. In the objective Bayesian framework, the selection of default prior distributions under such quasi-posterior distributions is an important problem. In this study, we provide some properties of reference and moment matching priors under the quasi-posterior distribution based on the -divergence. In particular, we show that the proposed priors are approximately robust under the condition on the contamination distribution without assuming any conditions on the contamination ratio. Some simulation studies are also presented. 相似文献