25 research outputs found

    The RAB2B-GARIL5 Complex Promotes Cytosolic DNA-Induced Innate Immune Responses

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    Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor that induces the IFN antiviral response. However, the regulatory mechanisms that mediate cGAS-triggered signaling have not been fully explored. Here, we show the involvement of a small GTPase, RAB2B, and its effector protein, Golgi-associated RAB2B interactor-like 5 (GARIL5), in the cGAS-mediated IFN response. RAB2B-deficiency affects the IFN response induced by cytosolic DNA. Consistent with this, RAB2B deficiency enhances replication of vaccinia virus, a DNA virus. After DNA stimulation, RAB2B colocalizes with stimulator of interferon genes (STING), the downstream signal mediator of cGAS, on the Golgi apparatus. The GTP-binding activity of RAB2B is required for its localization on the Golgi apparatus and for recruitment of GARIL5. GARIL5 deficiency also affects the IFN response induced by cytosolic DNA and enhances replication of vaccinia virus. These findings indicate that the RAB2B-GARIL5 complex promotes IFN responses against DNA viruses by regulating the cGAS-STING signaling axis

    Yam contributes to improvement of glucose metabolism in rats.

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    To investigate whether yam improves glucose metabolism, yam-containing diets were given to Wistar rats. In a short-term experiment, fasted-rats were given 1.0 g of a control and 20% yam-containing diets. At 60 min after start of the feeding, glucose level in the yam diet group was lower or tended to be lower than that in the control diet. Insulin levels at 30 min and 60 min were significantly lower than those in the control group. In a long-term experiment, a normal diet (N) or 25% high fat diets with (Y) or without 15% yam powder (HF) were given to rats for 4 weeks. At 4 weeks, in an oral glucose tolerance test, the area under the curve (AUC) of plasma glucose level was higher in the HF group than that in the N group, whereas those in the Y groups did not differ from that in the N group. Glycosylated hemoglobin levels had similar tendency to the AUCs. Plasma leptin levels in the Y groups were significantly higher than that in the N group. In conclusion, yam may contribute to improvement of glucose metabolism. Additionally, we speculated that leptin level is possibly involved in the insulin-response to yam diets

    Capturing structural changes of the S-1 to S-2 transition of photosystem II using time-resolved serial femtosecond crystallography

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    Photosystem II (PSII) catalyzes light-induced water oxidation through an S-i-state cycle, leading to the generation of di-oxygen, protons and electrons. Pumpprobe time-resolved serial femtosecond crystallography (TR-SFX) has been used to capture structural dynamics of light-sensitive proteins. In this approach, it is crucial to avoid light contamination in the samples when analyzing a particular reaction intermediate. Here, a method for determining a condition that avoids light contamination of the PSII microcrystals while minimizing sample consumption in TR-SFX is described. By swapping the pump and probe pulses with a very short delay between them, the structural changes that occur during the S-1-to-S-2 transition were examined and a boundary of the excitation region was accurately determined. With the sample flow rate and concomitant illumination conditions determined, the S-2-state structure of PSII could be analyzed at room temperature, revealing the structural changes that occur during the S-1-to-S-2 transition at ambient temperature. Though the structure of the manganese cluster was similar to previous studies, the behaviors of the water molecules in the two channels (O1 and O4 channels) were found to be different. By comparing with the previous studies performed at low temperature or with a different delay time, the possible channels for water inlet and structural changes important for the water-splitting reaction were revealed

    The RAB2B-GARIL5 Complex Promotes Cytosolic DNA-Induced Innate Immune Responses

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    Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor that induces the IFN antiviral response. However, the regulatory mechanisms that mediate cGAS-triggered signaling have not been fully explored. Here, we show the involvement of a small GTPase, RAB2B, and its effector protein, Golgi-associated RAB2B interactor-like 5 (GARIL5), in the cGAS-mediated IFN response. RAB2B-deficiency affects the IFN response induced by cytosolic DNA. Consistent with this, RAB2B deficiency enhances replication of vaccinia virus, a DNA virus. After DNA stimulation, RAB2B colocalizes with stimulator of interferon genes (STING), the downstream signal mediator of cGAS, on the Golgi apparatus. The GTP-binding activity of RAB2B is required for its localization on the Golgi apparatus and for recruitment of GARIL5. GARIL5 deficiency also affects the IFN response induced by cytosolic DNA and enhances replication of vaccinia virus. These findings indicate that the RAB2B-GARIL5 complex promotes IFN responses against DNA viruses by regulating the cGAS-STING signaling axis

    Light-induced structural changes and the site of O=O bond formation in PSII caught by XFEL

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    Photosystem II (PSII) is a huge membrane-protein complex consisting of 20 different subunits with a total molecular mass of 350 kDa for a monomer. It catalyses light-driven water oxidation at its catalytic centre, the oxygen-evolving complex (OEC). The structure of PSII has been analysed at 1.9 Å resolution by synchrotron radiation X-rays, which revealed that the OEC is a Mn4CaO5 cluster organized in an asymmetric, 'distorted-chair' form. This structure was further analysed with femtosecond X-ray free electron lasers (XFEL), providing the 'radiation damage-free' structure. The mechanism of O=O bond formation, however, remains obscure owing to the lack of intermediate-state structures. Here we describe the structural changes in PSII induced by two-flash illumination at room temperature at a resolution of 2.35 Å using time-resolved serial femtosecond crystallography with an XFEL provided by the SPring-8 ångström compact free-electron laser. An isomorphous difference Fourier map between the two-flash and dark-adapted states revealed two areas of apparent changes: around the QB/non-haem iron and the Mn4CaO5 cluster. The changes around the QB/non-haem iron region reflected the electron and proton transfers induced by the two-flash illumination. In the region around the OEC, a water molecule located 3.5 Å from the Mn4CaO5 cluster disappeared from the map upon two-flash illumination. This reduced the distance between another water molecule and the oxygen atom O4, suggesting that proton transfer also occurred. Importantly, the two-flash-minus-dark isomorphous difference Fourier map showed an apparent positive peak around O5, a unique μ4-oxo-bridge located in the quasi-centre of Mn1 and Mn4 (refs 4,5). This suggests the insertion of a new oxygen atom (O6) close to O5, providing an O=O distance of 1.5 Å between these two oxygen atoms. This provides a mechanism for the O=O bond formation consistent with that proposed previousl

    蔬菜水耕栽培の実用化に関する研究 XVII : 定植時の葉数がトマトの生育・収量におよぼす影響(農学部門)

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    トマトの水耕栽培における定植の適期を決定するために, 春作と秋作とにつき, 展開葉数が3,6,9,12枚時に定植して生育, 収量を比較した。品種は大型福寿, 培養液はれき耕用園試処方第1例の50%液を使用した。定植がおそくなると, 定植時および栽培終了時の草丈が大, 葉の大きさが小, 栽培終了時の植物体乾物含有率が大, 栽培前半の養水分吸収量が少, 開花数が少, 開花日がおそく, 開花より果実収穫までの日数が少となった。収量は, 春作では定植の早い区で大となったが, 秋作では定植のおそい区で大となった。Ohgata-Fukujyu tomatoes sown in sand and then water-cultured in nursery bed, were planted out in the culture bed at 3-, 6-, 9-, or 12-leaf stage, to determine the adequate age of transplants at planting out, in water culture. As the results of the later planting out, plant heights both at the time of planting out and the termination of experiment were higher, leaves were smaller, dry matter contents of plant component organs were higher, water and nutrient absorptions during early growth were lower, no. of flowers was less and no. of days required for fruit maturation was less, than those by the early planting out. The yield was lower and was often delayed by the later planting out in the spring crop, while it was higher and was delayed by a few days by the later planting out in the fall crop

    Theoretical analysis of angular distribution of scattering in nozzle components using a response-function method for proton spot-scanning therapy

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    In spot-scanning proton therapy, highly precise beam control is required in the treatment nozzle such that the proton beam does not spread out during transportation by restraining the divergence of the beam angle and spot size, simultaneously. In order to evaluate the beam-broadening behaviour induced by passing through the various nozzle components, we have developed a new method to calculate the angular divergence profile of a proton beam in the nozzle. The angular divergence of the proton beam for each nozzle component is calculated by the Monte Carlo simulation code, Geant4, assuming that the initial beam has no divergence. The angular divergence profiles generated in the various nozzle components are then fitted by the analytic function formula with triple Gaussian distributions. The fitted profiles can be treated like analytic response functions and the angular divergence profile in the nozzle can be easily and systematically calculated by using a convolution theorem. The beam-broadening behaviour during transportation in the nozzle is carefully evaluated. The beam profiles are well-characterized by the proposed angular divergence analysis, i.e. triple Gaussian profile analysis. The primary Gaussian part of the beam profile is mainly generated by air and dose monitors with plate electrode components. The secondary and tertiary Gaussian parts are so-called wide-angle scattering and generated mainly by spot-position and profile monitors with metal window and wire components. The scattering of the nozzle component can be analysed using the proposed response function method for the angular distribution. Multiple convolved angular scattering can be determined from the response function of the individual nozzle components. The angular distribution from small to large angle regions can then be quantitatively evaluated by the proposed method. The method is quite simple and generalized, and is a straightforward way to understand the nozzle and component characteristics related to the beam-broadening behaviour
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