An aryl hydrocarbon receptor induces VEGF expression through ATF4 under glucose deprivation in HepG2

BACKGROUND: Aryl hydrocarbon receptor (AhR) not only regulates drug-metabolizing enzyme expression but also regulates cancer malignancy. The steps to the development of malignancy include angiogenesis that is induced by tumor microenvironments, hypoxia, and nutrient deprivation. Vascular endothelial growth factor (VEGF) plays a central role in the angiogenesis of cancer cells, and it is induced by activating transcription factor 4 (ATF4). RESULTS: Recently, we identified that glucose deprivation induces AhR translocation into the nucleus and increases CYP1A1 and 1A2 expression in HepG2 cells. Here, we report that the AhR pathway induces VEGF expression in human hepatoblastoma HepG2 cells under glucose deprivation, which involves ATF4. ATF4 knockdown suppressed VEGF expression under glucose deprivation. Moreover, AhR knockdown suppressed VEGF and ATF4 expression under glucose deprivation at genetic and protein levels. CONCLUSIONS: The AhR-VEGF pathway through ATF4 is a novel pathway in glucose-deprived liver cancer cells that is related to the microenvironment within a cancer tissue affecting liver cancer malignancy

カイコBombyx moriの前部絹糸腺のアポトーシスにおける20-ヒドロキシエクジソンの二重支配

取得学位：博士(学術)，学位授与番号：博甲第396号，学位授与年月日：平成13年3月22日,学位授与年：200

Early specification of ascidian larval motor neurons

AbstractIn the tadpole larvae of the ascidian Halocynthia roretzi, six motor neurons, Moto-A, -B, and -C (a pair of each), are localized proximal to the caudal neural tube and show distinct morphology and innervation patterns. To gain insights into early mechanisms underlying differentiation of individual motor neurons, we have isolated an ascidian homologue of Islet, a LIM type homeobox gene. Earliest expression of Islet was detected in a pair of bilateral blastomeres on the dorsal edge of the late gastrula. At the neurula stage, this expression began to disappear and more posterior cells started to express Islet. Compared to expression of a series of motor neuron genes, it was confirmed that early Islet-positive blastomeres are the common precursors of Moto-A and -B, and late Islet-positive cells in the posterior neural tube are the precursors of Moto-C. Overexpression of Islet induced ectopic expression of motor neuron markers, suggesting that Islet is capable of regulating motor neuron differentiation. Since early expression of Islet colocalizes with that of HrBMPb, the ascidian homologue of BMP2/4, we tested a role of BMP in specification of the motor neuron fate. Overexpression of HrBMPb led to expansion of Lim and Islet expression toward the central area of the neural plate, and microinjection of mRNA coding for a dominant-negative BMP receptor weakened the expression of these genes. Our results suggest that determination of the ascidian motor neuron fate takes place at late gastrula stage and local BMP signaling may play a role in this step

Large and homogeneous mass enhancement in the rattling-induced superconductor KOs2_2O6_6

We have determined the Fermi surface in KOs$_2$O$_6$ ($T_c$ = 9.6 K and $B_{c2} \sim$ 32 T) via de Haas-van Alphen (dHvA) oscillation measurements and a band structure calculation. We find effective masses up to 26(1) $m_e$ ($m_e$ is the free electron mass), which are unusually heavy for compounds where the mass enhancement is mostly due to electron-phonon interactions. Orbit-resolved mass enhancement parameters $\lambda_{dHvA}$ are large but fairly homogeneous, concentrated in the range 5 -- 8. We discuss origins of the large homogeneous mass enhancement in terms of rattling motion of the K ions.Comment: Minor revisions, Fig.2a modifie

Flower visitor fauna of the narrow endemic lily Lilium rubellum Baker in a lowland habitat in Yamagata, northern Japan

Floral visitor fauna of the narrow endemic lily Lilium rubellum was examined in a lowland habitat in Kaminoyama City, Yamagata Prefecture, northern Japan. Flowers of L. rubellum bloomed from early to late June. During 23 h of observing floral visitors, 64 insects were detected on L. rubellum flowers. Although coleopteran insects were most frequently found on L. rubellum flowers, they did not seem to be effective pollinators because of their body size. Bees were less frequently observed than coleopteran insects, but all individuals contacted sexual organs in L. rubellum flowers. Syrphid flies were seen less frequently, but they were also considered effective pollinators. From our observations, L. rubellum is a bee-pollinated species of the genus Lilium. Bee pollination has also been recorded in a species of Lilium sect. Archelirion, L. japonicum var. abeanum. The floral characteristics of L. japonicum var. abeanum (e.g., pinkish color, relatively small and tubular corolla, and lateral insertion of anthers into the corolla) were similar to those of L. rubellum and the character combination may be related to the bee-pollination mode in Lilium. key words： bee pollination, Bombus, Ceratina, flower visitor fauna, Lilium japonicum var. abeanum, Lilium rubellum, nitidulid beetle, syrphid fl

Fermi level tuning of Ag-doped Bi2Se3 topological insulator

The temperature dependence of the resistivity (rho) of Ag-doped Bi2Se3 (AgxBi2-xSe3) shows insulating behavior above 35 K, but below 35 K, rho suddenly decreases with decreasing temperature, in contrast to the metallic behavior for non-doped Bi2Se3 at 1.5-300 K. This significant change in transport properties from metallic behavior clearly shows that the Ag doping of Bi2Se3 can effectively tune the Fermi level downward. The Hall effect measurement shows that carrier is still electron in AgxBi2-xSe3 and the electron density changes with temperature to reasonably explain the transport properties. Furthermore, the positive gating of AgxBi2-xSe3 provides metallic behavior that is similar to that of non-doped Bi2Se3, indicating a successful upward tuning of the Fermi level

Supersymmetric Wilson Loops in N=6 Super Chern-Simons-matter theory

We study supersymmetric Wilson loop operators in ABJM theory from both sides of the AdS_4/CFT_3 correspondence. We first construct some supersymmetric Wilson loops. The perturbative computations are performed in the field theory side at the first two orders. A fundamental string solution ending on a circular loop is also studied.Comment: 21 pages, 6 figures; v2: minor changes; v3, 21 pages, 4 figures, major revisions, published versio

De Novo Mutations in GNAO1, Encoding a Gαo Subunit of Heterotrimeric G Proteins, Cause Epileptic Encephalopathy

Heterotrimeric G proteins, composed of α, β, and γ subunits, can transduce a variety of signals from seven-transmembrane-type receptors to intracellular effectors. By whole-exome sequencing and subsequent mutation screening, we identified de novo heterozygous mutations in GNAO1, which encodes a Gαo subunit of heterotrimeric G proteins, in four individuals with epileptic encephalopathy. Two of the affected individuals also showed involuntary movements. Somatic mosaicism (approximately 35% to 50% of cells, distributed across multiple cell types, harbored the mutation) was shown in one individual. By mapping the mutation onto three-dimensional models of the Gα subunit in three different complexed states, we found that the three mutants (c.521A>G [p.Asp174Gly], c.836T>A [p.Ile279Asn], and c.572_592del [p.Thr191_Phe197del]) are predicted to destabilize the Gα subunit fold. A fourth mutant (c.607G>A), in which the Gly203 residue located within the highly conserved switch II region is substituted to Arg, is predicted to impair GTP binding and/or activation of downstream effectors, although the p.Gly203Arg substitution might not interfere with Gα binding to G-protein-coupled receptors. Transient-expression experiments suggested that localization to the plasma membrane was variably impaired in the three putatively destabilized mutants. Electrophysiological analysis showed that Gαo-mediated inhibition of calcium currents by norepinephrine tended to be lower in three of the four Gαo mutants. These data suggest that aberrant Gαo signaling can cause multiple neurodevelopmental phenotypes, including epileptic encephalopathy and involuntary movements