Vascular Endothelial Adrenomedullin-RAMP2 System Is Essential for Vascular Integrity and Organ Homeostasis

信州大学博士（医学）・学位論文・平成25年3月31日授与（甲第935号）・小山 晃英Background-Revealing the mechanisms underlying the functional integrity of the vascular system could make available novel therapeutic approaches. We previously showed that knocking out the widely expressed peptide adrenomedullin (AM) or receptor activity-modifying protein 2 (RAMP2), an AM-receptor accessory protein, causes vascular abnormalities and is embryonically lethal. Our aim was to investigate the function of the vascular AM-RAMP2 system directly. Methods and Results-We generated endothelial cell-specific RAMP2 and AM knockout mice (E-RAMP2(-/-) and E-AM(-/-)). Most E-RAMP2(-/-) mice died perinatally. In surviving adults, vasculitis occurred spontaneously. With aging, E-RAMP2(-/-) mice showed severe organ fibrosis with marked oxidative stress and accelerated vascular senescence. Later, liver cirrhosis, cardiac fibrosis, and hydronephrosis developed. We next used a line of drug-inducible E-RAMP2(-/-) mice (DI-E-RAMP2(-/-)) to induce RAMP2 deletion in adults, which enabled us to analyze the initial causes of the aforementioned vascular and organ damage. Early after the induction, pronounced edema with enhanced vascular leakage occurred. In vitro analysis revealed the vascular leakage to be caused by actin disarrangement and detachment of endothelial cells. We found that the AM-RAMP2 system regulates the Rac1-GTP/RhoA-GTP ratio and cortical actin formation and that a defect in this system causes the disruption of actin formation, leading to vascular and organ damage at the chronic stage after the gene deletion. Conclusions-Our findings show that the AM-RAMP2 system is a key determinant of vascular integrity and homeostasis from prenatal stages through adulthood. Furthermore, our models demonstrate how endothelial cells regulate vascular integrity and how their dysregulation leads to organ damage. (Circulation. 2013;127:842-853.)ArticleCIRCULATION. 127(7):842-853 (2013)journal articl

4D Imaging and Diffraction Dynamics of Single-Particle Phase Transition in Heterogeneous Ensembles

In this Letter, we introduce conical-scanning dark-field imaging in four-dimensional (4D) ultrafast electron microscopy to visualize single-particle dynamics of a polycrystalline ensemble undergoing phase transitions. Specifically, the ultrafast metal–insulator phase transition of vanadium dioxide is induced using laser excitation and followed by taking electron-pulsed, time-resolved images and diffraction patterns. The single-particle selectivity is achieved by identifying the origin of all constituent Bragg spots on Debye–Scherrer rings from the ensemble. Orientation mapping and dynamic scattering simulation of the electron diffraction patterns in the monoclinic and tetragonal phase during the transition confirm the observed behavior of Bragg spots change with time. We found that the threshold temperature for phase recovery increases with increasing particle sizes and we quantified the observation through a theoretical model developed for single-particle phase transitions. The reported methodology of conical scanning, orientation mapping in 4D imaging promises to be powerful for heterogeneous ensemble, as it enables imaging and diffraction at a given time with a full archive of structural information for each particle, for example, size, morphology, and orientation while minimizing radiation damage to the specimen

A influência da estrutura de propriedade e controle sobre o valor de mercado corporativo no Brasil

O modelo brasileiro de governança corporativa é caracterizado pela elevada concentração na estrutura societária que, em geral, culmina na sobreposição da propriedade e da administração das companhias. Segundo a literatura, o acúmulo de ações pelo(s) controlador(es) pode impactar o desempenho corporativo devido ao efeito-alinhamento (ou incentivo) e ao efeito-entrincheiramento. A princípio, a presença de grandes acionistas estaria associada a benefícios para a organização, uma vez que poderia aumentar a eficácia do monitoramento da gestão. Todavia, patamares muito elevados de concentração acionária podem permitir que os controladores dominem o processo decisório da corporação, o que poderia resultar na expropriação da riqueza dos acionistas minoritários. A relevância da estrutura societária como mecanismo interno dos sistemas de governança corporativa motivou a realização do presente estudo. Este artigo teve como objetivo testar se a concentração de propriedade e controle influencia o valor de mercado corporativo. Para tanto, foi utilizado um painel não balanceado para o período de 2001 a 2010, composto por 237 empresas brasileiras não financeiras de capital aberto, que somou 1.199 observações. Foram empregados modelos dinâmicos de regressão, estimados pelo Método dos Momentos Generalizado Sistêmico (MMG-Sis), para mitigar possíveis fontes de endogeneidade como a omissão de variáveis, o efeito-feedback e a simultaneidade. Constatou-se a existência de relação quadrática entre concentração no direito sobre o fluxo de caixa do acionista controlador e o valor de mercado das firmas. Ademais, os resultados indicam que o valor de mercado corrigido das ações do maior acionista captou o efeito-incentivo, enquanto a concentração no direito de voto capturou o efeito-entrincheiramento

Jahn-Teller Effect of Cu-Ferrite Films by Solid Reaction

Copper iron oxide (CuFe2O4 : Cu-ferrite) thin film was prepared on a glass substrate by vacuum evaporation and solid reaction, and annealed at 400 °C in the air. The obtained film was identified by X-ray diffraction analysis as Cu-ferrite film having a tetragonal lattice. The axial ratio (c/a) of the film was 1.507 and was larger than that of ASTM data because the lattice distortion of the films seems to be large by difference of a preparation method. The temperature dependence of the magnetization and conductivities of the film showed remarkable changes at about 360°C, which were considered to be caused by phase transition due to the Jahn-Teller effect