Helicobacter pylori Exploits Host Membrane Phosphatidylserine for Delivery, Localization, and Pathophysiological Action of the CagA Oncoprotein

SummaryWhen delivered into gastric epithelial cells via type IV secretion, Helicobacter pylori CagA perturbs host cell signaling and thereby promotes gastric carcinogenesis. However, the mechanisms of CagA delivery, localization, and action remain poorly understood. We show that direct contact of H. pylori with epithelial cells induces externalization of the inner leaflet enriched host phospholipid, phosphatidylserine, to the outer leaflet of the host plasma membrane. CagA, which is exposed on the bacterial surface via type IV secretion, interacts with the externalized phosphatidylserine to initiate its entry into cells. CagA delivery also requires energy-dependent host cell processes distinct from known endocytic pathways. Within polarized epithelial cells, CagA is tethered to the inner leaflet of the plasma membrane through interaction with phosphatidylserine and binds the polarity-regulating host kinase PAR1/MARK to induce junctional and polarity defects. Thus, host membrane phosphatidylserine plays a key role in the delivery, localization, and pathophysiological action of CagA

White Patchy Materials Formed in a Scoriacious Road-cut Profile on Miyake Island(Plant Production Science Soil Science)

Sulfurous gas, sulfur or sulfates are frequently contained in volcanic ejecta. We found white patchy materials (WPM) in a road-cut profile on Miyake Island, Japan. The layer containing WPM consists of scoria deposit in 1874. The major materials we identified in the WPM were CaSO_4・2H_2O and amorphous silica according to X-ray diffraction and energy dispersive X-ray analyses. A possible process for crystallization of CaSO_4・2H_2O in the WPM is the dissolution of CaSO_4・2H_2O contained in the overlying 2000 ash and its re-precipitation on the surface of the scoriacious road-cut profile. Emission of sulfur dioxide gas, converted to sulfuric acid in water, has been so abundant since the 2000 eruption that we further examined reaction products between crushed scoria and dilute H_2SO_4 (0.1-2.5mol L^). CaSO_4・2H_2O was also identified in the reaction products as well as alunogen, iron sulfate, etc. Because alunogen is highly soluble in water, CaSO_4・2H_2O was the major crystalline product after rinsing with water

A noise spectral estimation method based on VAD and recursive averaging using new adaptive parameters for non-stationary noise environments

金沢大学理工研究域　電子情報学系A noise spectral estimation method, which is used in spectral suppression noise cancellers, is proposed for highly non-stationary noise environments. Speech and non-speech frames are detected by using the entropy-based voice activity detector (VAD). An adaptive normalization parameter and a variable threshold are newly introduced for the VAD. They are very useful for rapid change in the noise spectrum and power. Furthermore, a recursive averaging method is applied to estimating the noise spectrum in the non-speech frames. In this method, an adaptive smoothing parameter is proposed, based on speech presence probability. Simulations are carried out by using many kinds of noises, including white, babble, car, pink, factory and tank, which are changed from one to the other. The segmental SNR is improved by 2.0 ~3.8dB, and noise spectral estimation error is improved by 3.2 ~ 4.7dB for the white noise and the babble noise, which are changed from one to the other

Biomimetic design of an α-ketoacylphosphonium-based light-activated oxygenation auxiliary

The biomimetic design of a transition metal complex based on the iron(IV)-oxo porphyrin π-cation radical species in cytochrome P450 enzymes has been studied extensively. Herein, we translate the functions of this iron(IV)-oxo porphyrin π-cation radical species to an α-ketoacyl phosphonium species comprised of non-metal atoms and utilize it as a light-activated oxygenation auxiliary for ortho-selective oxygenation of anilines. Visible light irradiation converts the α-ketoacyl phosphonium species to the excited state, which acts as a transiently generated oxidant. The intramolecular nature of the process ensures high regioselectivity and chemoselectivity. The auxiliary is easily removable. A one-pot protocol is also described

Effect of Initial Grain Size on Dynamically Recrystallized Grain Size in AZ31 Magnesium Alloy

The effect of initial grain size on dynamically recrystallized grain size (DRX grain size) is examined in AZ31 magnesium alloy with four kinds of initial grain sizes. When the average grain size after the high-temperature compression test is plotted against Zenner-Hollomon parameter (Z-parameter), initial grain size dependence on DRX grain size appears only in the specimen with large initial grain size in the low Z region, but not in the specimen with small grain size or in high Z region. When the grain size measured only in recrystallized region is plotted against Z-parameter, initial grain size dependence on DRX grain size does not appear. From these results, it is concluded that there is no initial grain size dependence on DRX grain size when the DRX proceeds to some degree, because the DRX grain size becomes constant for a given Zvalue. The initial grain size dependence on DRX grain size observed in the low Z region would be related to the rotation of basal plane perpendicular to the compression axis during deformation before the DRX grains have been developed sufficiently

Diagnostic accuracy of narrow-band imaging and pit pattern analysis significantly improved for less-experienced endoscopists after an expanded training program

Background: Previous reports assessing diagnostic skill using narrow-band imaging (NBI) and pit pattern analysis for colorectal polyps involved only highly experienced endoscopists. Objective: To evaluate diagnostic skills of less-experienced endoscopists (LEE group) for. differentiation of diminutive colorectal polyps by using NBI and pit pattern analysis with and without magnification after an expanded training program. Design: Prospective study. Patients: This study involved 32 patients with 44 colorectal polyps (27 adenomas and 17 hyperplastic polyps) of 5 mm that were identified and analyzed by using conventional colonoscopy as well as non-magnification and magnification NBI and chromoendoscopy followed by endoscopic removal for histopathological analysis. Intervention: Before a training course, 220 endoscopic images were distributed in randomized order to residents with no prior endoscopy experience (NEE group) and to the LEE group, who had performed colonoscopies for more than 5 years but had never used NBI. The 220 images were also distributed to highly experienced endoscopists (HEE group) who had routinely used NBI for more than 5 years. The images were distributed to the NEE and LEE groups again after a training class. Magnification NBI and chromoendoscopy images were assessed by using the Sano and Kudo classification systems, respectively. Main Outcome Measurements: Diagnostic accuracy and interobserver agreement for each endoscopic modality in each group. Results: Diagnostic accuracy was significantly higher, and kappa (kappa) values improved in the LEE group for NBI with high magnification after expanded training. Diagnostic accuracy and kappa values when using high-magnification NBI were highest among endoscopic techniques for the LEE group after such training and the HEE group (accuracy 90% vs 93%; kappa = 0.79 vs 0.85, respectively). Limitations: Study involved only polyps of <= 5 mm. Conclusion: Using high-magnification NBI increased the differential diagnostic skill of the LEE group after expanded training so that it was equivalent to that of the HEE group

Evaluation of transporter-mediated hepatobiliary transport of newly developed ¹⁸F-labeled pitavastatin derivative, PTV-F1, in rats by PET imaging

Quantitative evaluations of the functions of uptake and efflux transporters directly in vivo is desired to understand an efficient hepatobiliary transport of substrate drugs. Pitavastatin is a substrate of organic anion transporting polypeptides (OATPs) and canalicular efflux transporters; thus, it can be a suitable probe for positron-emission tomography (PET) imaging of hepatic transporter functions. To characterize the performance of [¹⁸F]PTV-F1, an analogue of pitavastatin, we investigated the impact of rifampicin (a typical OATP inhibitor) coadministration or Bcrp (breast cancer resistance protein) knockout on [¹⁸F]PTV-F1 hepatic uptake and efflux in rats by PET imaging. After intravenous administration, [¹⁸F]PTV-F1 selectively accumulated in the liver, and the radioactivity detected in plasma, liver, and bile mainly derived from the parent PTV-F1 during the PET study (∼40 min). Coadministration of rifampicin largely decreased the hepatic uptake of [¹⁸F]PTV-F1 by 73%. Because of its lower clearance in rats, [¹⁸F]PTV-F1 is more sensitive for monitoring changes in hepatic OATP1B function that other previously reported OATP1B PET probes. Rifampicin coadministration also significantly decreased the biliary excretion of radioactivity by 65%. Bcrp knockout did not show a significant impact on its biliary excretion.[¹⁸F]PTV-F1 enables quantitative analysis of the hepatobiliary transport system for organic anions

Effect of Texture of AZ31 Magnesium Alloy Sheet on Mechanical Properties and Formability at High Strain Rate

The mechanical properties and formability of AZ31 magnesium alloy strips having different textures were investigated at a high strain rate based on that occuring in mass production by press forming. Forming at a high strain rate on the order of 10 0 s À1 requires a high temperature of over 473 K. To obtain accurate stress-strain curves, a high-speed testing machine that can maintain a constant true strain rate was used, and the change in gauge length on a test piece in a furnace was measured during the testing time of about 0.5 s. For the specimens, rolled strips consisting of fine grains (about 10 mm) and an extruded strip consisting of coarse grains (about 40 mm) were used. The {0001} textures of the extruded strip and one of the rolled strips were strongly oriented parallel to the rolled surface, but the texture of another rolling strip had two peaks that were inclined at 5 $15 deg in front of and behind the rolling direction. At the high strain rate of 10 0 s À1 , elongation decreased for every specimen. Nevertheless, a limiting drawing ratio (LDR) of 2:1$ 2:2 was obtained under uniform heating above 503 K in all the specimens except for the extruded strip. The high LDR of the rolled strip having a two-peak texture was maintained in forming at temperatures down to 473 K, in contrast to the LDR of the strongly oriented rolled strip, which reduced rapidly when formed at temperatures less than 503 K

Severe sepsis caused by Aeromonas hydrophila in a patient using tocilizumab: a case report

<p>Abstract</p> <p>Introduction</p> <p><it>Aeromonas </it>species do not commonly cause disease in humans. However, when disease is seen, it often occurs in patients with underlying immunosuppression or malignancy and has a high fatality rate.</p> <p>Case presentation</p> <p>A 72-year-old Japanese woman with rheumatoid arthritis treated with tocilizumab (which has an immunosuppressive effect) presented with severe epigastric pain. She had a fever with chills, hypotension and jaundice. She was diagnosed with acute suppurative cholangitis and treated with cefoperazone-sulbactam and an endoscopic drainage was performed. Jaundice was slightly improved, but the shock state and inflammatory reactions were prolonged as typical of septic shock. On the second day after admission, an electrocardiogram showed ST segment elevation and echocardiography showed ventricular wall dysfunction. Coronary arteries were patent in coronary angiography and she was diagnosed with stress-induced cardiomyopathy. Blood cultures showed <it>Aeromonas hydrophila</it>. A stool culture was negative for <it>A. hydrophila</it>. On day six, her white blood cell count and neutrophils were normalized and cefoperazone-sulbactam treatment was halted. Left ventricular function normalized on day twelve and a laparoscopic cholecystectomy for cholelithiasis was performed on the 16th day of hospitalization. A culture from the bile showed <it>A. hydrophila</it>. Eighteen days after surgery, tocilizumab treatment was restarted and there were no complications. Two months after restarting tocilizumab, our patient is stable without any serious events.</p> <p>Conclusion</p> <p>We present a rare case of <it>A. hydrophila </it>sepsis and acute suppurative cholangitis in an elderly patient with gallstones and rheumatoid arthritis using tocilizumab. This clinical course may suggest that preemptive treatment for cholelithiasis prior to using molecular-targeting agents might be feasible in elderly patients.</p