Synthesis of potent chemical inhibitors of dynamin GTPase

Dynamin is a key regulatory protein in clathrin mediated endocytosis. Compared to genetic or immunological tools, small chemical dynamin inhibitors such as dynasore have the potential to study the dynamic nature of endocytic events in cells. Dynasore inhibits dynamin GTPase activity and transferrin uptake at IC(50) similar to 15 mu M but use in some biological applications requires more potent inhibitor than dynasore. Here, we chemically modified the side chains of dynasore and found that two derivatives, DD-6 and DD-11 more potently inhibited transferrin uptake (IC(50): 4.00 mu M for DD-6, 2.63 mu M for DD-11) and dynamin GTPase activity (IC(50:) 5.1 mu M for DD-6, 3.6 mu M for DD-11) than dynasore. The effect was reversible and they were washed more rapidly out than dynasore. TIRF microscopy showed that they stabilize the clathrin coats on the membrane. Our results indicated that new dynasore derivatives are more potent inhibitor of dynamin, displaying promise as leads for the development of more effective analogues for broader biological applications. (c) 2010 Elsevier Ltd. All rights reserved.Odell LR, 2009, CHEMMEDCHEM, V4, P1182, DOI 10.1002/cmdc.200900054Hill TA, 2009, J MED CHEM, V52, P3762, DOI 10.1021/jm900036mMiyauchi K, 2009, CELL, V137, P433, DOI 10.1016/j.cell.2009.02.046de Beco S, 2009, P NATL ACAD SCI USA, V106, P7010, DOI 10.1073/pnas.0811253106Lu WB, 2009, J BIOL CHEM, V284, P1930, DOI 10.1074/jbc.M803691200Otsuka A, 2009, BIOCHEM BIOPH RES CO, V378, P478, DOI 10.1016/j.bbrc.2008.11.066Kirchhausen T, 2008, METHOD ENZYMOL, V438, P77, DOI 10.1016/S0076-6879(07)38006-3Quan A, 2007, MOL PHARMACOL, V72, P1425, DOI 10.1124/mol.107.034207Newton AJ, 2006, P NATL ACAD SCI USA, V103, P17955, DOI 10.1073/pnas.0606212103Macia E, 2006, DEV CELL, V10, P839, DOI 10.1016/j.devcel.2006.04.002Roux A, 2006, NATURE, V441, P528, DOI 10.1038/nature04718Hill T, 2005, J MED CHEM, V48, P7781, DOI 10.1021/jm040208lCao H, 2005, NAT CELL BIOL, V7, P483, DOI 10.1038/ncb1246Abazeed ME, 2005, J BIOL CHEM, V280, P4442, DOI 10.1071/jbc.M412553200Hill TA, 2004, BIOORG MED CHEM LETT, V14, P3275, DOI 10.1016/j.bmcl.2004.03.096Nichols B, 2003, J CELL SCI, V116, P4707, DOI 10.1242/jcs.00840Nabi IR, 2003, J CELL BIOL, V161, P673, DOI 10.1083/jcb.200302028Hill E, 2001, J CELL BIOL, V152, P309DAMKE H, 1994, J CELL BIOL, V127, P915

Ultrasonography of the ankle joint

Ankle disorders are a relatively common pathological condition, and ankle injuries account for approximately 14% of sports-related orthopedic emergency visits. Various imaging modalities can be used to make a diagnosis in cases of ankle pain; however, ultrasound (US) has several benefits for the evaluation of ankle pain, especially in the tendons, ligaments, and nerves of the ankle. The purpose of this article is to review the common causes of ankle pathology, with particular reference to US features. In addition, the importance of a dynamic evaluation and a stress test with US is emphasized

Position Classification of the Endotracheal Tube with Automatic Segmentation of the Trachea and the Tube on Plain Chest Radiography Using Deep Convolutional Neural Network

Background: This study aimed to develop an algorithm for multilabel classification according to the distance from carina to endotracheal tube (ETT) tip (absence, shallow > 70 mm, 30 mm ≤ proper ≤ 70 mm, and deep position < 30 mm) with the application of automatic segmentation of the trachea and the ETT on chest radiographs using deep convolutional neural network (CNN). Methods: This study was a retrospective study using plain chest radiographs. We segmented the trachea and the ETT on images and labeled the classification of the ETT position. We proposed models for the classification of the ETT position using EfficientNet B0 with the application of automatic segmentation using Mask R-CNN and ResNet50. Primary outcomes were favorable performance for automatic segmentation and four-label classification through five-fold validation with segmented images and a test with non-segmented images. Results: Of 1985 images, 596 images were manually segmented and consisted of 298 absence, 97 shallow, 100 proper, and 101 deep images according to the ETT position. In five-fold validations with segmented images, Dice coefficients [mean (SD)] between segmented and predicted masks were 0.841 (0.063) for the trachea and 0.893 (0.078) for the ETT, and the accuracy for four-label classification was 0.945 (0.017). In the test for classification with 1389 non-segmented images, overall values were 0.922 for accuracy, 0.843 for precision, 0.843 for sensitivity, 0.922 for specificity, and 0.843 for F1-score. Conclusions: Automatic segmentation of the ETT and trachea images and classification of the ETT position using deep CNN with plain chest radiographs could achieve good performance and improve the physician’s performance in deciding the appropriateness of ETT depth

Catalytic Copyrolysis of Cellulose and Thermoplastics over HZSM‑5 and HY

Catalytic pyrolysis with HZSM-5 is a promising method for the production of renewable aromatic hydrocarbons directly from biomass, even though the aromatic yields are still very low. Recent studies have shown that cofeeding of biomass with plastic significantly improves the aromatic yield due to high hydrogen content in plastic. In an effort to determine the influence of the zeolite pore size and the molecular diameter of cofeeding plastic on the aromatic production, catalytic copyrolysis of cellulose and thermoplastics, including random polypropylene (PP) and linear low density polyethylene (LLDPE) was conducted over HZSM-5 and HY catalysts. Thermogravimetric (TG) results showed that maximum decomposition temperature of PP was shifted to the higher temperature when PP was copyrolyzed with cellulose over HZSM-5 because the diffusion of PP molecules was hindered by the cellulose-derived coke and char. This hindering effect was attenuated by employing LLDPE as the cofeeding plastic due to its smaller molecular diameter than PP, and/or applying HY due to its larger pore size than HZSM-5. Heart-cut-evolved gas analysis (EGA)-GC/MS and flash pyrolysis-GC/FID were used to monitor the detailed product distribution and yields. The synergistic aromatic formation was easily achieved over HY catalyst for both PP and LLDPE, demonstrating the effectiveness of the larger pore zeolite for the catalytic copyrolysis. In contrast, HZSM-5 was very effective for the enhancement of aromatic production under severe reaction conditions, such as high catalyst to feed ratio (i.e., 10:1) or high pyrolysis temperature (i.e., 600 °C)