the adenosine A 2B receptor is a critical protein in intestinal water secretion. in the present study, we screened compound libraries to identify inhibitors of the A 2B receptor and evaluated their effect on adenosine-induced intestinal fluid secretion. The screening identified the dihydropyridine calcium antagonists nifedipine and nisoldipine. Their respective affinities for the A 2B receptor (K i value) were 886 and 1,399 nM. Nifedipine and nisoldipine, but not amlodipine or nitrendipine, inhibited both calcium mobilization and adenosine-induced cAMp accumulation in cell lines. Moreover, adenosine injection into the lumen significantly increased fluid volume in the colonic loop of wild-type mice but not A 2B receptor-deficient mice. PSB-1115, a selective A 2B receptor antagonist, and nifedipine prevented elevated adenosine-stimulated fluid secretion in mice. Our results may provide useful insights into the structure-activity relationship of dihydropyridines for A 2B receptor. As colonic fluid secretion by adenosine seems to rely predominantly on the A 2B receptor, nifedipine could be a therapeutic candidate for diarrhoea-related diseases.Adenosine is an important mediator of multiple functions, such as intestinal secretion, contraction, inflammation, and sensation in the gastrointestinal tract 1-3 . Among adenosine receptors, the A 2B receptor is highly expressed in the colon and has critical roles in pathological conditions 4 . In general, adenosine levels and A 2B receptor expression are low under normal conditions, but increase in response to ischemia, inflammation, and tissue injuries. The activated A 2B receptor stimulates intestinal water secretion and sensation or modulates inflammatory response and colonic motility 5,6 . As a result, it is associated with the development of gastrointestinal diseases, such as irritable bowel syndrome (IBS), secretary diarrhoea, and inflammatory bowel disease 7,8 . Therefore, this receptor has attracted substantial attention as a therapeutic target. Although pharmacological and molecular tools, including genetically modified mouse models, have revealed multiple functions of the A 2B receptor, such as immunomodulation, relaxation of smooth muscle, and intestinal secretion 5,9 , our understanding of its biology remains unclear.Diarrhoea is caused by bacterial and viral infections, inflammatory processes, drugs, genetic disorders, and abnormal intestinal secretion or electrolyte absorption 10,11 . However, the pathophysiology of diarrhoea is not fully understood. Chloride secretion into the lumen following activation of the cystic fibrosis transmembrane conductance regulator (CFTR) channel in intestinal epithelial cells plays a crucial role in secretory diarrhoea 1,12 . Several studies suggest that A 2B receptor activation causes fluid secretion into the lumen. In vitro studies using colonic epithelial cells have demonstrated that adenosine increases luminal water volume through apical or basolateral www.nature.com/scientificreports www.nature.com/scientificreports/ similar ...

The deployment of Internet of Things (IoT) services in a variety of fields has recently resulted in a rapid rise in the number of connected devices and the traffic volume generated by those devices across networks. In these cases, the problems of the Internet become remarkable. To address these issues, Pub/Sub type communication appears to be a viable option. This communication provides simplified communication sequences and is independent of IP flows. However, it may allow a DDoS attack because the Domain Name System (DNS) is not required and incoming traffic can be admitted without protection. This study proposes the traffic limitation function by Token Bucket Filter on Pub/Sub type communication. This study intends to utilize MQ Telemetry Transport (MQTT) as one of the most popular Pub/Sub type communication. It also reports the development of the prototype system, including the proposal and evaluation using this prototype system.

In MQTT for IoT communication, multiple brokers should be deployed to accommodate a number of end devices. However, routing mechanisms among these brokers have yet to be specified. In this paper, a new routing mechanism for this purpose is proposed. This mechanism is aimed at layer 2 base control. It provides co-operations with MQTT and the Spanning Tree Protocol and invokes a traffic reduction and simplified transfer by an independent IP flow. In this paper, the detailed communication sequences are proposed, and the reasonability of the proposed mechanism based on a performance evaluation using prototyping is highlighted.

We developed a hybrid model membrane by combining natural and polymeric phospholipid bilayers, and silicone elastomer (polydimetylsiloxan; PDMS). A micropatterned membrane composed of polymeric and fluid bilayers was generated on a glass substrate. The polymeric bilayer was made of a diacetylene phospholipid, and had a reactive amine moiety on the surface. We bonded PDMS microstructures onto the polymeric bilayer by attaching biotin onto the surface and using the biotin-streptavidin linkage. We also employed lipid vesicles as a bonding agent between polymeric bilayer and PDMS. The model membrane achieved a unique 3D structure for confining and transporting molecules in a small space between the membrane and PDMS, which can be used as a novel biosensing platform. 2P206 ベシクル基盤分子ロボットのための分子センサーの開発Development of a molecular sensor for vesicle-based molecular robots Koh-ichiroh Shohda, Akira Suyama (The University of Tokyo)A molecular robot based on a vesicle or a gel as a body is composed of molecular sensors, molecular computers, and molecular actuators in the molecular robotics project. We develop a molecular sensor that is a conjugated molecule of DNA strands and a hydrophobic molecule. The sensor molecule located into a membrane of giant unilamellar vesicle can hybridize with a complementary DNA/RNA strand that represents an environmental signal. The hybridization approximates two sensor molecules, consequently a single-stranded DNA will be released into an inner water pool of vesicle. The released DNA will be a trigger for molecular computers encapsulated in GUV-based molecular robots. Cells contain thousands of lipid varieties. To know the lipid roles, each lipid behavior is important. Lipid binding probes have been used to visualize their target lipids. To characterize the interaction between lipids and probes, we try to construct the system based on quartz crystal microbalance (QCM). Although the simple method for the fixation of lipid membrane on sensor is vesicle fusion, the method is not suited for the complex composition of lipids. Therefore, we applied the linker based liposome fixation. In this method, the sensor was covered with planar lipid bilayers containing linkers and target liposomes were fixed with linkers. We are able to characterize the binding kinetics of lipid probe in the flexible liposome condition (composition, size, density). Bacteriorhodopsin (bR) is a light-driven proton pump that forms twodimensional crystal, called purple membrane (PM). While PM is a flat membrane in a native environment, PM spontaneously converts its membrane structure into a uniformly-sized vesicle (50 nm in diameter) in the presence of a detergent. So far, the molecular arrangement in the bRvesicle is undissolved. Here, we applied high-speed atomic force microscopy to directly visualize the molecular arrangement of bR in the bR-vesicle. On mica surface, the bR-vesicle collapsed to form a flat membrane with a thickness of 8 nm. In high-magnification images, honeycomb structure was observed in the bR-vesicle. This m...

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