Identification of Physiologically Active Substances as Novel Ligands for MRGPRD

Mas-related G-protein coupled receptor member D (MRGPRD) is a G protein-coupled receptor (GPCR) which belongs to the Mas-related GPCRs expressed in the dorsal root ganglia (DRG). In this study, we investigated two novel ligands in addition to beta-alanine: (1) beta-aminoisobutyric acid, a physiologically active substance, with which possible relation to tumors has been seen together with beta-alanine; (2) diethylstilbestrol, a synthetic estrogen hormone. In addition to the novel ligands, we found that transfection of MRGPRD leads fibroblast cells to form spheroids, which would be related to oncogenicity. To understand the MRGPRD novel character, oncogenicity, a large chemical library was screened in order to obtain MRGPRD antagonists to utilize in exploring the character. The antagonist in turn inhibited the spheroid proliferation that is dependent on MRGPRD signaling as well as MRGPRD signals activated by beta-alanine. The antagonist, a small-molecule compound we found in this study, is a potential anticancer agent

MRGD, a MAS-related G-protein Coupled Receptor, Promotes Tumorigenisis and Is Highly Expressed in Lung Cancer

To elucidate the function of MAS-related GPCR, member D (MRGD) in cancers, we investigated the in vitro and in vivo oncogenic function of MRGD using murine fibroblast cell line NIH3T3 in which MRGD is stably expressed. The expression pattern of MRGD in clinical samples was also analyzed. We found that overexpression of MRGD in NIH3T3 induced focus formation and multi-cellular spheroid formation, and promoted tumors in nude mice. In other words, overexpression of MRGD in NIH3T3 induced the loss of contact inhibition, anchorage-independent growth and in vivo tumorigenesis. Furthermore, it was found that the ligand of MRGD, beta-alanine, enhanced spheroid formation in MRGD-expressing NIH3T3 cells. From investigation of clinical cancer tissues, we found high expression of MRGD in several lung cancers by immunohistochemistry as well as real time PCR. Based on these results, MRGD could be involved in tumorigenesis and could also be a novel anticancer drug target

Vegetation and Colonization Status of Mycorrhizal and Endophytic Fungi in Plant Species on Acidic Barren at Crater Basin of Volcano Esan in Hokkaido, Japan

We investigated the colonization status of mycorrhizal and endophytic fungi in roots of plants established on an acidic barren at volcano Esan, Hokkaido, Japan. In total, 87 individuals of 21 plant taxa were investigated in four different vegetation sites and the surrounding area. Ericaceous plants such as Empetrum nigrum var. japonicum, Ledum palustre var. diversipilosum, Vaccinium vitis-idaea var. minus and Loiseleuria procumbens were the main colonizers at the study sites and dominated under even the most severe conditions of low soil moisture and nutrient content. They were associated with ericoid mycorrhizal (ERM) fungi at all vegetation sites and erratically with dark septate endophytic (DSE) fungi. They commonly associated together with arbuscular mycorrhizal (AM) fungi only at sites where Sasa senanensis dominated. Among the ericaceous plants, only Enkianthus campanulatus associated with AM and DSE fungi and had no associations with ERM fungi. Other herbaceous and woody plants associated commonly with AM or erratically with DSE fungi, except for Carex sp. and Polygonum spp. which erratically associated with AM and DSE fungi. Mycorrhizal associations were common in representative vegetation on the crater basin of Mt. Esan. In particular, ERM associations might play a significant role in invasion and establishment of ericaceous plants, and also in the development of plant communities in the harsh environment at Mt. Esan

Microstructural transitions in resistive random access memory composed of molybdenum oxide with copper during switching cycles

The switching operation of a Cu/MoOx/TiN resistive random access memory (ReRAM) device was investigated using in situ transmission electron microscopy (TEM), where the TiN surface was slightly oxidized (ox-TiN). The relationship between the switching properties and the dynamics of the ReRAM microstructure was confirmed experimentally. The growth and/or shrinkage of the conductive filament (CF) can be classified into two set modes and two reset modes. These switching modes depend on the device's switching history, factors such as the amount of Cu inclusions in the MoOx layer and the CF geometry. High currents are needed to produce an observable change in the CF. However, sharp and stable switching behaviour can be achieved without requiring such a major change. The local region around the CF is thought to contribute to the ReRAM switching process

IHC analysis of MRGD expression.

<p>Cell block samples were used to confirm the antibody specificity in immunostaining. HEK293/αvβ3 cells transfected with MRGD expression vector (<b>A</b>) or Mock vector (<b>B</b>) are shown. <b>C.</b> The representative staining of lung adenocarcinoma which is positive for MRGD.</p