258 research outputs found

    Shibusawa Eiichi\u27s View of Japan\u27s Foreign Affairs: Focusing on His Influences on the Meiji Government

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    From the mid-nineteenth century, Asia, including China and Japan, has been involved in the trend of modernization that was triggered by the activities of European and American powers in this area. In a time of drastic changes, Shibusawa Eiichi (1840-1931) assumed several roles successively: he served as retainer during the bakumatsu period, as official in the Meiji government, and afterwards as businessman, philanthropist, and non-official diplomat. During his service in the Meiji government from 1869 to 1873 and as an entrepreneur from 1873 to 1909, Shibusawa played a key role in devising economic and diplomatic policies for the Meiji government. He is even considered a major designer of modem Japanese economic systems and society. This paper examines Shibusawa Eiichi\u27s view of Japan\u27s foreign affairs and focuses on the way he influenced the Meiji government

    Synthesis of a Trivalent P-Chloro-Dithienophosphole and its Reactivity with Organometallic Reagents

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    P-chloro-dithieno[3,2-b:2’,3’-d]phosphole was synthesized and isolated from the reaction of an aminophosphole and HCl. Developed to act as a common starting material for P-functionalized phospholes, the compound exhibits a surprising reactivitiy by generating dimeric biphospholes. Despite this apparent sensitivity, when reacting with organolithium and Grignard reagents, a series of differently P-functionalized dithieno[3,2-b:2’,3’-d]phospholes was accessible. Unexpectedly, organolithium reagents showed reduced reactivity with the chlorophosphole, limiting yields of the desired products due to the competing dimerization. Nonetheless, P- functionalized phospholes were isolated from reactions of the title compound with both Grignard and organolithium reagents in yields equivalent to, or higher, than by previous methods. A bithiophene- bridged bisphosphole system was also successfully synthesized without the necessity of generating a bis(dichlorophosphino) reagent. Finally, the isolated P-functionalized phospholes were analyzed for their photophysical properties. In general, these compounds are strong absorbers in the UV/visible range of the optical spectrum. The phospholes’ emissions were consistent with several previously reported, however, typically with low quantum yields.NSERC, CFI, CRC, Alberta Innovates - Technology Future

    A Select Combination of Clinically Relevant Phytoestrogens Enhances Estrogen Receptor β-Binding Selectivity and Neuroprotective Activities in Vitro and in Vivo

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    We have previously shown that a number of naturally occurring phytoestrogens and derivatives were effective to induce some measures of neuroprotective responses but at a much lower magnitude than those induced by the female gonadal estrogen 17β-estradiol. In the present study, we sought to investigate whether a combination of select phytoestrogens could enhance neural responses without affecting the reproductive system. We performed a range of comparative analyses of the estrogen receptor (ER) α/β binding profile, and in vitro to in vivo estrogenic activities in neural and uterine tissues induced by clinically relevant phytoestrogens: genistein, daidzein, equol, and IBSO03569, when used alone or in combination. Our analyses revealed that both the ERα/β binding profile and neural activities associated with individual phytoestrogens are modifiable when used in combination. Specifically, the combination of genistein plus daidzein plus equol resulted in the greatest binding selectivity for ERβ and an overall improved efficacy/safety profile when compared with single or other combined formulations, including: 1) an approximate 30% increase in ERβ-binding selectivity (83-fold over ERα); 2) a greater effect on neuronal survival against toxic insults in primary neurons; 3) an enhanced activity in promoting neural proactive defense mechanisms against neurodegeneration, including mitochondrial function and β-amyloid degradation; and 4) no effect on uterine growth. These observations suggest that select phytoestrogens in combination have the therapeutic potential of an alternative approach to conventional estrogen therapy for long-term safe use to reduce the increased risk of cognitive decline and neurodegenerative disease associated with menopause in women. A combination of genistein, daidzein, and equol enhances estrogen receptor β-binding selectivity and estrogenic activities in promoting neuronal survival and brain defense mechanisms without impact on uterine growth.This work was supported by grants from the Alzheimer’s Association (to L.Z.), Kenneth T. and Eileen L. Norris Foundation, and Bensussen Translational Research Fund (to R.D.B.)

    Is Melanoma a stem cell tumor? Identification of neurogenic proteins in trans-differentiated cells

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    BACKGROUND: Although several genes and proteins have been implicated in the development of melanomas, the molecular mechanisms involved in the development of these tumors are not well understood. To gain a better understanding of the relationship between the cell growth, tumorigenesis and differentiation, we have studied a highly malignant cat melanoma cell line that trans-differentiates into neuronal cells after exposure to a feline endogenous retrovirus RD114. METHODS: To define the repertoire of proteins responsible for the phenotypic differences between melanoma and its counterpart trans-differentiated neuronal cells we have applied proteomics technology and compared protein profiles of the two cell types and identified differentially expressed proteins by 2D-gel electrophoresis, image analyses and mass spectrometry. RESULTS: The melanoma and trans-differentiated neuronal cells could be distinguished by the presence of distinct sets of proteins in each. Although approximately 60–70% of the expressed proteins were shared between the two cell types, twelve proteins were induced de novo after infection of melanoma cells with RD114 virus in vitro. Expression of these proteins in trans-differentiated cells was significantly associated with concomitant down regulation of growth promoting proteins and up-regulation of neurogenic proteins (p = < 0.001). Based on their physiologic properties, >95% proteins expressed in trans-differentiated cells could be associated with the development, differentiation and regulation of nervous system cells. CONCLUSION: Our results indicate that the cat melanoma cells have the ability to differentiate into distinct neuronal cell types and they express proteins that are essential for self-renewal. Since melanocytes arise from the neural crest of the embryo, we conclude that this melanoma arose from embryonic precursor stem cells. This model system provides a unique opportunity to identify domains of interactions between the expressed proteins that halt the tumorigenic potential of melanoma cells and drive them toward neurogenerative pathways involved in early neurogenesis. A better understanding of these proteins in a well-coordinated signaling network would also help in developing novel approaches for suppression of highly malignant tumors that arise from stem-like embryonic cells

    Sonocrystallisation of Lactose in an Aqueous System

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    Although research on sonocrystallisation of lactose has been reported in the literature (yield and crystal size), the effect of ultrasound variables on nucleation and growth rate of lactose have not been studied. In this study, lactose crystallisation with ultrasound was compared with mechanical agitation using the induction time method at 22 °C. Ultrasound had a significant effect in reducing induction times and narrowing the metastable zone width but had no effect on individual crystal growth rate or morphology. A rapid decrease in induction time was observed up to 0.46 Wg-1 power density. Sonication up to 3 min decreased the induction time, but no further reduction was observed beyond 3 min. It was not possible to generate the nucleation rates achieved by sonication using agitation alone. 1 min sonication at 0.46 Wg1 power density followed by continuous stirring was found to be the optimum under the experimental conditions tested

    On the Germination of Shibusawa Eiichi’s View of Japan’s Foreign Affairs

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    Shibusawa Eiichi (1840-1931), arguably the most famous entrepreneur of modern Japan, lived through four epochal periods of Japanese history: the end of the Tokugawa, the Meiji, Taisho, and first years of the Showa eras. Shibusawa played a decisive role in a number of fields in the modernization of Japan, including politics, economics, culture, and social welfare. In the wave of modernization that swept Asia in the early nineteenth century, Shibusawa served as retainer during the bakumatsu, as official in the Meiji government, businessman, philanthropist, and non-official diplomat. This paper examines the germination of Shibusawa’s view of Japan’s foreign affairs.東アジアの歴史と動

    御所浦島の水産養殖業について―その歴史と現在―

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    Ovariectomy Induces a Shift in Fuel Availability and Metabolism in the Hippocampus of the Female Transgenic Model of Familial Alzheimer's

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    This is the published version. Copyright 2013 Public Library of Science.Previously, we demonstrated that reproductive senescence in female triple transgenic Alzheimer's (3×TgAD) mice was paralleled by a shift towards a ketogenic profile with a concomitant decline in mitochondrial activity in brain, suggesting a potential association between ovarian hormone loss and alteration in the bioenergetic profile of the brain. In the present study, we investigated the impact of ovariectomy and 17β-estradiol replacement on brain energy substrate availability and metabolism in a mouse model of familial Alzheimer's (3×TgAD). Results of these analyses indicated that ovarian hormones deprivation by ovariectomy (OVX) induced a significant decrease in brain glucose uptake indicated by decline in 2-[18F]fluoro-2-deoxy-D-glucose uptake measured by microPET-imaging. Mechanistically, OVX induced a significant decline in blood-brain-barrier specific glucose transporter expression, hexokinase expression and activity. The decline in glucose availability was accompanied by a significant rise in glial LDH5 expression and LDH5/LDH1 ratio indicative of lactate generation and utilization. In parallel, a significant rise in ketone body concentration in serum occurred which was coupled to an increase in neuronal MCT2 expression and 3-oxoacid-CoA transferase (SCOT) required for conversion of ketone bodies to acetyl-CoA. In addition, OVX-induced decline in glucose metabolism was paralleled by a significant increase in Aβ oligomer levels. 17β-estradiol preserved brain glucose-driven metabolic capacity and partially prevented the OVX-induced shift in bioenergetic substrate as evidenced by glucose uptake, glucose transporter expression and gene expression associated with aerobic glycolysis. 17β-estradiol also partially prevented the OVX-induced increase in Aβ oligomer levels. Collectively, these data indicate that ovarian hormone loss in a preclinical model of Alzheimer's was paralleled by a shift towards the metabolic pathway required for metabolism of alternative fuels in brain with a concomitant decline in brain glucose transport and metabolism. These findings also indicate that estrogen plays a critical role in sustaining brain bioenergetic capacity through preservation of glucose metabolism
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