Myristic Acid, A Side Chain of Phorbol Myristate Acetate (PMA), Can Activate Human Polymorphonuclear Leukocytes to Produce Oxygen Radicals More Potently than PMA

Myristic acid (MyA), which is a saturated fatty acid (C14:0) and a side chain of phorbol 12-myristate 13-acetate (PMA), was examined if MyA stimulates human polymorphonuclear leukocytes (PMNs) to release oxygen radicals comparable to PMA by applying electron paramagnetic resonance (EPR)-spin-trapping method. When MyA was added to isolated human PMNs, spin adducts of 5,5-dimethyl-1-pyrroline-N-oxide (DMPO)-OH and DMPO-OOH were time-dependently observed. The amounts of these spin adducts were larger than those of PMNs stimulated by PMA. These results clearly show that MyA is more potent agent to prime human PMNs than PMA, in a point of view of not only O2·− but also ·OH production. This fact calls attention that too much intake of MyA that is known to be contained vegetable oils can lead to crippling effect through uncontrolled production of reactive oxygen species

aPKC and DOC2b in glucose transport

Aims/introduction: Double C2 domain protein b (DOC2b), one of the synaptotagmins, has been shown to translocate to the plasma membrane, and to initiate membrane-fusion processes of vesicles containing glucose transporter 4 proteins on insulin stimulation. However, the mechanism by which DOC2b is regulated remains unclear. Herein, we identified the upstream regulatory factors of DOC2b in insulin signal transduction. We also examined the role of DOC2b on systemic homeostasis using DOC2b knockout (KO) mice. Materials and Methods: We first identified DOC2b binding proteins by immunoprecipitation and mutagenesis experiments. Then, DOC2b KO mice were generated by disrupting the first exon of the DOC2b gene. In addition to the histological examination, glucose metabolism was assessed by measuring parameters on glucose/insulin tolerance tests. Insulin-stimulated glucose uptake was also measured using isolated soleus muscle and epididymal adipose tissue. Results: We identified an isoform of atypical protein kinase C (protein kinase C iota) that can bind to DOC2b and phosphorylates one of the serine residues of DOC2b (S34). This phosphorylation is essential for DOC2b translocation. DOC2b KO mice showed insulin resistance and impaired oral glucose tolerance on insulin and glucose tolerance tests, respectively. Insulin-stimulated glucose uptake was impaired in isolated soleus muscle and epididymal adipose tissues from DOC2b KO mice. Conclusions: We propose a novel insulin signaling mechanism by which protein kinase C iota phosphorylates DOC2b, leading to glucose transporter 4 vesicle translocation, fusion and facilitation of glucose uptake in response to insulin. The present results also showed DOC2b to play important roles in systemic glucose homeostasis

Wide-bandgap GaN-based watt-class photonic-crystal lasers

青色GaN系フォトニック結晶レーザーの高出力・高ビーム品質動作に成功 --次世代の高品位レーザー加工、高輝度照明、水中LiDAR等の実現に向けて--. 京都大学プレスリリース. 2022-11-04.Short-wavelength (blue-violet-to-green) lasers with high power and high beam quality are required for various applications including the machining of difficult-to-process materials and high-brightness illuminations and displays. Promising light sources for such applications are wide-bandgap GaN-based photonic-crystal surface-emitting lasers (PCSELs), which are based on two-dimensional resonance in the photonic crystal. Developments of these devices have lagged behind those of longer-wavelength GaAs-based PCSELs, because device designs for achieving robust two-dimensional resonance and a nanofabrication process that avoids introducing disorders have remained elusive for wide-bandgap GaN-based materials. Here, we address these issues and successfully realize GaN-based PCSELs with high, watt-class (>1 W) output power and a circular, single-lobed beam with a very narrow (~0.2°) divergence angle at blue wavelengths. In addition, we demonstrate continuous-wave operation with a high output power (~320 mW) and a high beam quality (M²~1). Our results will enable the use of GaN-based PCSELs in the above-mentioned applications

Myosin motor Myo1c and its receptor NEMO/IKK-γ promote TNF-α–induced serine307 phosphorylation of IRS-1

Tumor necrosis factor-α (TNF-α) signaling through the IκB kinase (IKK) complex attenuates insulin action via the phosphorylation of insulin receptor substrate 1 (IRS-1) at Ser307. However, the precise molecular mechanism by which the IKK complex phosphorylates IRS-1 is unknown. In this study, we report nuclear factor κB essential modulator (NEMO)/IKK-γ subunit accumulation in membrane ruffles followed by an interaction with IRS-1. This intracellular trafficking of NEMO requires insulin, an intact actin cytoskeletal network, and the motor protein Myo1c. Increased Myo1c expression enhanced the NEMO–IRS-1 interaction, which is essential for TNF-α– induced phosphorylation of Ser307–IRS-1. In contrast, dominant inhibitory Myo1c cargo domain expression diminished this interaction and inhibited IRS-1 phosphorylation. NEMO expression also enhanced TNF-α–induced Ser307–IRS-1 phosphorylation and inhibited glucose uptake. In contrast, a deletion mutant of NEMO lacking the IKK-β–binding domain or silencing NEMO blocked the TNF-α signal. Thus, motor protein Myo1c and its receptor protein NEMO act cooperatively to form the IKK–IRS-1 complex and function in TNF-α–induced insulin resistance

Temporal subtraction CT with nonrigid image registration improves detection of bone metastases by radiologists: results of a large-scale observer study

To determine whether temporal subtraction (TS) CT obtained with non-rigid image registration improves detection of various bone metastases during serial clinical follow-up examinations by numerous radiologists. Six board-certified radiologists retrospectively scrutinized CT images for patients with history of malignancy sequentially. These radiologists selected 50 positive and 50 negative subjects with and without bone metastases, respectively. Furthermore, for each subject, they selected a pair of previous and current CT images satisfying predefined criteria by consensus. Previous images were non-rigidly transformed to match current images and subtracted from current images to automatically generate TS images. Subsequently, 18 radiologists independently interpreted the 100 CT image pairs to identify bone metastases, both without and with TS images, with each interpretation separated from the other by an interval of at least 30 days. Jackknife free-response receiver operating characteristics (JAFROC) analysis was conducted to assess observer performance. Compared with interpretation without TS images, interpretation with TS images was associated with a significantly higher mean figure of merit (0.710 vs. 0.658; JAFROC analysis, P = 0.0027). Mean sensitivity at lesion-based was significantly higher for interpretation with TS compared with that without TS (46.1% vs. 33.9%; P = 0.003). Mean false positive count per subject was also significantly higher for interpretation with TS than for that without TS (0.28 vs. 0.15; P < 0.001). At the subject-based, mean sensitivity was significantly higher for interpretation with TS images than that without TS images (73.2% vs. 65.4%; P = 0.003). There was no significant difference in mean specificity (0.93 vs. 0.95; P = 0.083). TS significantly improved overall performance in the detection of various bone metastases

Infection risk in hemodialysis patient

Chronic care patients undergoing hemodialysis for treatment of end-stage renal failure experience higher rates of bloodstream-associated infection due to the patients' compromised immune system and management of the bloodstream through catheters. Staphylococcus species are a common cause of hemodialysis catheter-related bloodstream infections. We investigated environmental bacterial contamination of dialysis wards and contamination of hemodialysis devices to determine the source of bacteria for these infections. All bacterial samples were collected by the swab method and the agarose stamp method. And which bacterium were identified by BBL CRYSTAL Kit or 16s rRNA sequences. In our data, bacterial cell number of hemodialysis device was lower than environment of patient surrounds. But Staphylococcus spp. were found predominantly on the hemodialysis device (46.8%), especially on areas frequently touched by healthcare-workers (such as Touch screen). Among Staphylococcus spp., Staphylococcus epidermidis was most frequently observed (42.1% of Staphylococcus spp.), and more surprising, 48.2% of the Staphylococcus spp. indicated high resistance for methicillin. Our finding suggests that hemodialysis device highly contaminated with bloodstream infection associated bacteria. This study can be used as a source to assess the risk of contamination-related infection and to develop the cleaning system for the better prevention for bloodstream infections in patients with hemodialysis

Particle control in long-pulse discharge using divertor pumping in LHD

Density control is crucial for maintaining stable confined plasma. Divertor pumping, where neutral particles are compressed and exhausted in the divertor region, was developed for this task for the Large Helical Device. In this study, neutral particle pressure, which is related to recycling, was systematically scanned in the magnetic configuration by changing the magnetic axis position. High neutral particle pressure and compression were obtained in the divertor for a high plasma electron density and the inner magnetic axis configuration. Density control using divertor pumping with gas puffing was applied to electron cyclotron heated plasma in the inner magnetic axis configuration, which provides high neutral particle compression and exhaust in the divertor. Stable plasma density and electron temperature were maintained with divertor pumping. A heat analysis shows that divertor pumping did not affect edge electron heat conductivity, but it led to low electron heat conductivity in the core caused by electron-internal-transport-barrier-like formation

Integrated radiation monitoring and interlock system for the LHD deuterium experiments

The Large Helical Device (LHD) successfully started the deuterium experiment in March 2017, in which further plasma performance improvement is envisaged to provide a firm basis for the helical reactor design. Some major upgrades of facilities have been made for safe and productive deuterium experiments. For radiation safety, the tritium removal system, the integrated radiation monitoring system, and the access control system have been newly installed. Each system has new interlock signals that will prevent any unsafe plasma operation or plant condition. Major interlock extensions have been implemented as a part of the integrated radiation monitoring system, which also has an inter-connection to the LHD central operation and control system. The radiation monitoring system RMSAFE (Radiation Monitoring System Applicable to Fusion Experiments) is already operating for monitoring γ(X)-rays in LHD. Some neutron measurements have been additionally applied for the deuterium experiments. The LHD data acquisition system LABCOM can acquire and process 24 h every day continuous data streams. Since γ(X)-ray and neutron measurements require higher availability, the sensors, controllers, data acquisition computers, network connections, and visualization servers have been designed to be duplicated or multiplexed for redundancy. The radiation monitoring displays in the LHD control room have been carefully designed to have excellent visual recognition, and to make users immediately aware of several alerts regarding the dose limits. The radiation safety web pages have been also upgraded to always show both dose rates of γ(X)-rays and neutrons in real time

Research and development of exclusive equipment for cell-free and concentrated ascites reinfusion therapy (CART) by medical-industrial, hospital-university, and multifarious worker cooperation

Cell-free and concentrated ascites reinfusion therapy（CART）is an effective and safe therapy for patients with refractory ascites or pleural effusion. CART was initially indicated for cirrhotic ascites, and has come to be widely used for malignant ascites. Recently, cancer therapy that applies cancer cells obtained by filtration process is considered, and CART attracts attention as one of the important therapies to support future cancer therapy. However, the numbers of CART in Japan is not sufficient because the equipment for CART is high price and large. Additionally, the specialized medical staff such as clinical engineers is necessary for CART because of complicated operation. Therefore, we think that development of next-generation type equipment for CART that can be performed safely, easily, and reliably is necessary. We could develop the exclusive equipment for CART according to the project management by multifarious worker cooperation in five years

Overview of transport and MHD stability study: focusing on the impact of magnetic field topology in the Large Helical Device

The progress in the understanding of the physics and the concurrent parameter extension in the large helical device since the last IAEA-FEC, in 2012 (Kaneko O et al 2013 Nucl. Fusion 53 095024), is reviewed. Plasma with high ion and electron temperatures (Ti(0) ~ Te(0) ~ 6 keV) with simultaneous ion and electron internal transport barriers is obtained by controlling recycling and heating deposition. A sign flip of the nondiffusive term of impurity/momentum transport (residual stress and convection flow) is observed, which is associated with the formation of a transport barrier. The impact of the topology of three-dimensional magnetic fields (stochastic magnetic fields and magnetic islands) on heat momentum, particle/impurity transport and magnetohydrodynamic stability is also discussed. In the steady state operation, a 48 min discharge with a line-averaged electron density of 1 × 1019 m−3 and with high electron and ion temperatures (Ti(0) ~ Te(0) ~ 2 keV), resulting in 3.36 GJ of input energy, is achieved