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Nina Westphal, Gabriele Loers, David Lutz, Thomas Theis, Ralf Kleene, Melitta Schachner
Polysialic acid (PSA) and its major protein carrier, the neural cell adhesion molecule NCAM, play important roles in many nervous system functions during development and in adulthood. Here, we show that a PSA-carrying NCAM fragment is generated at the plasma membrane by matrix metalloproteases and transferred to the cell nucleus via endosomes and the cytoplasm. Generation and nuclear import of this fragment in cultured cerebellar neurons is induced by a function-triggering NCAM antibody and a peptide comprising the effector domain (ED) of myristoylated alanine-rich C kinase substrate (MARCKS) which interacts with PSA within the plane of the plasma membrane...
August 17, 2017: Scientific Reports
Hong-Guang Xie, Yu-Meng Jia, Ting Tai, Jin-Zi Ji
Clopidogrel is one of the most frequently prescribed drugs worldwide; however, the presence of clopidogrel resistance and high susceptibility to genetic variations and drug interactions are facilitating the development of other antiplatelet drugs. To overcome clopidogrel resistance, several promising clopidogrel analogues have been developed in China, such as vicagrel (and its deuterated analogues), PLD-301, and W1. These novel chemical analogues are all characterized by much faster and more efficient bioconversion to clopidogrel thiolactone (or 2-oxo-clopidogrel, the precursor of clopidogrel active metabolite) in the intestine than clopidogrel through bypassing the first-step P450-mediated oxidation of clopidogrel in the liver...
August 4, 2017: Journal of Cardiovascular Pharmacology
Kimberly Stieglitz
BACKGROUND: In recent years human phospholipase D enzymes (PLD1 and PLD2 isozymes) have emerged as drug targets for various diseases such as cardiovascular disease, cancer, infectious diseases and neurodegenerative conditions such as Alzheimer's and Parkinson's disease. The interest in PLD as a drug target is due to the fact that PLD enzymes belong to a superfamily of phospholipases that are essential to intracellular and extracellular signaling. Many bioactive lipid signaling molecules are generated by these enzymes including phosphatidic and lysophosphatidic acid, arachidonic acid, and diacylglycerol (DAG)...
August 15, 2017: Current Drug Discovery Technologies
Premal H Thaker, William E Brady, Heather A Lankes, Kunle Odunsi, William H Bradley, Kathleen N Moore, Carolyn Y Muller, Khursheed Anwer, Russell J Schilder, Ronald D Alvarez, Paula M Fracasso
OBJECTIVE: The study's purpose was to assess safety and efficacy of escalating doses of weekly GEN-1 with pegylated liposomal doxorubicin (PLD) in patients with recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal cancers (EOC). METHODS: Patients had persistent or recurrent platinum-resistant EOC. The trial was a standard 3+3 phase I dose escalation design with patients receiving intravenous PLD 40mg/m(2) (dose level 1 and 2) or 50mg/m(2) (dose level 3) every 28days and intraperitoneal GEN-1 at 24mg/m(2) (dose level 1) or 36mg/m(2) (dose level 2 and 3) on days 1, 8, 15, and 22 of a 28day cycle...
August 9, 2017: Gynecologic Oncology
N Blank, I Laskov, R Kessous, L Kogan, S Lau, I A Sebag, Walter H Gotlieb, L Rudski
BACKGROUND: Pegylated liposomal doxorubicin (PLD) is used as a second-line therapy for gynecologic cancers, with a better short-term toxicity profile compared to doxorubicin or other anthracyclines. METHODS: We screened 14 patients with recurrent gynecologic cancers, who underwent prolonged treatment with large cumulative doses of PLD for overt or subtle signs of cardiotoxicity (CTX) using standard and advanced echocardiography techniques [3D volumetric method for left ventricular ejection fraction (LVEF) and left ventricular/right ventricular global longitudinal strain]...
August 11, 2017: Cancer Chemotherapy and Pharmacology
Jia Guo, Samantha J Holdsworth, Audrey P Fan, Marc R Lebel, Zungho Zun, Ajit Shankaranarayanan, Greg Zaharchuk
PURPOSE: To compare performance of sequential and Hadamard-encoded pseudocontinuous arterial spin labeling (PCASL). MATERIALS AND METHODS: Monte Carlo simulations and in vivo experiments were performed in 10 healthy subjects. Field strength and sequence: 5-delay sequential (5-del. Seq.), 7-delay Hadamard-encoded (7-del. Had.), and a single-delay (1-del.) PCASL, without and with vascular crushing at 3.0T. The errors and variations of cerebral blood flow (CBF) and arterial transit time (ATT) from simulations and the CBF and ATT estimates and variations in gray matter (GM) with different ATT ranges were compared...
August 9, 2017: Journal of Magnetic Resonance Imaging: JMRI
Ilham Smyej, Sandra De Jonghe, Adriana Looszova, Geert Mannens, Tom Verhaeghe, Sandy Thijssen, Sofie Starckx, Ann Lampo, Marie-Claude Rouan
Bedaquiline (BDQ) is an antibiotic to treat pulmonary multidrug-resistant tuberculosis (MDR-TB). Studies up to 39 weeks were conducted orally in dogs to assess the toxicity and pharmacokinetics of BDQ and its N-desmethyl metabolite (D-BDQ). Phospholipidosis (PLD) seen in the monocytic phagocytic system was considered an adaptive change. Skeletal muscle, heart, stomach, liver, and pancreas toxicities with D-BDQ as the main contributor were associated with a less-than-dose-proportional increase in plasma exposure and an overproportional tissue uptake of BDQ and D-BDQ at high-dose levels...
January 1, 2017: Toxicologic Pathology
L F M van de Laarschot, J P H Drenth
Polycystic liver disease (PLD) is a heterogeneous genetic condition. PKD1 and PKD2 germline mutations are found in patients with autosomal dominant polycystic kidney disease (ADPKD). Autosomal dominant polycystic liver disease (ADPLD) is associated with germline mutations in PRKCSH, SEC63, LRP5, and recently ALG8, and SEC61. GANAB mutations are found in both patient groups. Loss of heterozygosity of PLD-genes in cyst epithelium contributes to the development of hepatic cysts. A genetic interaction network is implied in hepatic cystogenesis that connects the endoplasmic glycoprotein control mechanisms and polycystin expression and localization...
August 4, 2017: Biochimica et Biophysica Acta
Sajal Chakraborti, Jaganmay Sarkar, Rajabrata Bhuyan, Tapati Chakraborti
Phospholipase D (PLD) catalyzes the hydrolysis of phosphatidylcholine to produce phosphatidic acid (PA) which in some cell types play a pivotal role in agonist-induced increase in NADPH oxidase-derived [Formula: see text]production. Involvement of ADP ribosylation factor (Arf) in agonist-induced activation of PLD is known for smooth muscle cells of systemic arteries, but not in pulmonary artery smooth muscle cells (PASMCs). Additionally, role of cytohesin in this scenario is unknown in PASMCs. We, therefore, determined the involvement of Arf and cytohesin in U46619-induced stimulation of PLD in PASMCs, and the probable mechanism by which curcumin, a natural phenolic compound, inhibits the U46619 response...
August 5, 2017: Molecular and Cellular Biochemistry
Xiaolong Cao, Mansi Gulati, Haobo Jiang
Insect serine proteases (SPs) and serine protease homologs (SPHs) participate in digestion, defense, development, and other physiological processes. In mosquitoes, some clip-domain SPs and SPHs (i.e. CLIPs) have been investigated for possible roles in antiparasitic responses. In a recent test aimed at improving quality of gene models in the Anopheles gambiae genome using RNA-seq data, we observed various discrepancies between gene models in AgamP4.5 and corresponding sequences selected from those modeled by Cufflinks, Trinity and Bridger...
August 2, 2017: Insect Biochemistry and Molecular Biology
Jin-Long Zhang, Kai Yuan, Mao-Qiang Wang, Jie-Yu Yan, Hai-Nan Xin, Yan Wang, Feng-Yong Liu, Yan-Hua Bai, Zhi-Jun Wang, Feng Duan, Jin-Xin Fu
BACKGROUND: Currently, treatment of symptomatic polycystic liver disease (PLD) is still a challenging problem, especially for these patients who are not feasible for surgery. Minimally invasive options such as laparoscopic fenestration and percutaneous cyst aspiration with sclerotherapy demonstrated disappointing results due to multiple lesions. Because the cysts in PLD are mostly supplied from hepatic arteries but not from portal veins, transcatheter arterial embolization (TAE) of the hepatic artery branches that supply the major hepatic cysts can lead to shrinkage of the cyst and liver size, relieve symptoms, and improve nutritional status...
August 20, 2017: Chinese Medical Journal
Zhipeng Wu, Jun Zhu
A metal-insulator-metal structure resistive switching device based on H0.5Z0.5O₂ (HZO) thin film deposited by pulse laser deposition (PLD) has been investigated for resistive random access memory (RRAM) applications. The devices demonstrated bistable and reproducible unipolar resistive switching (RS) behaviors with an extremely high OFF/ON ratio over 5400. The retention property had no degradation at 6 × 10⁴ s. The current-voltage characteristics of the HZO samples showed a Schottky emission conduction in the high voltage region (Vreset < V < Vset), while at the low voltage region (V < Vreset), the ohmic contact and space charge limited conduction (SCLC) are suggested to be responsible for the low and high resistance states, respectively...
March 22, 2017: Materials
Xingpeng Liu, Bin Peng, Wanli Zhang, Jun Zhu, Xingzhao Liu, Meng Wei
In order to develop a film electrode for the surface acoustic wave (SAW) devices working in high temperature, harsh environments, novel AlN/Pt/ZnO multilayers were prepared using pulsed laser deposition (PLD) systems on langasite (LGS) substrates. The AlN film was used as a protective layer and the ZnO buffer layer was introduced to improve the crystal quality of Pt films. The results show that the resistances of Pt and AlN/Pt film electrodes violently increase above 600 °C and 800 °C, respectively, while the resistances of AlN/Pt/ZnO electrodes have more stable electrical resistance from room temperature to 1000 °C...
January 16, 2017: Materials
Ya-Hui Hsu, Hsing-Wei Hung, Shu-Ching Chen
BACKGROUND: Anti-cancer chemotherapy may cause skin-toxicity reactions. Different types of cooling packages affect chemotherapy-induced skin toxicity reactions differently. PURPOSE: To evaluate the effects of cooling packing care on chemotherapy-induced skin toxicity reactions in cancer patients receiving chemotherapy. METHODS: A systematic review approach was used. Searches were conducted in databases including Cochrane Library, Embase, MEDLINE, PubMed and Airiti Library using the keywords "chemotherapy cutaneous toxicity", "chemotherapy skin reaction", "chemotherapy skin toxicity", "frozen glove", "frozen sock", "cooling packaging care", "ice gloves", "ice socks", "usual care", "severity", "comfort", "satisfaction", "severity", and "comfort"...
August 2017: Hu Li za Zhi the Journal of Nursing
Kaustav Majumder, John R Spratt, Christopher T Holley, Samit S Roy, Rebecca J Cogswell, Kenneth Liao, Ranjit John
BACKGROUND: Liver dysfunction in left ventricular assist device (LVAD) recipients is common both before and after implantation. Postoperative liver dysfunction (PLD) develops in some LVAD recipients without preoperative liver dysfunction. The aim of this study was to assess clinical outcomes in such patients. METHODS: Records of all patients undergoing implantation of a HeartMate II (HM II, St. Jude Medical, Inc, Minneapolis, MN) LVAD at a single center at the University of Minnesota from January 2005 through June 2014 were analyzed...
July 28, 2017: Annals of Thoracic Surgery
Partha P Dey, Alika Khare
In the present report, the structural, compositional, morphological, and photoluminescence properties of nanostructured non-stoichiometric silicon oxide (nc-Si:SiO2 or SiOx) thin films fabricated by pulsed-laser ablation of silicon in the presence of oxygen pressure, from 10(-4) to 0.5 mbar, are presented. X-ray diffraction spectra and Raman spectra confirmed the formation of nanocrystalline Si within the films while electron diffraction X-ray spectroscopy confirmed the increase in oxygen content with increasing O2 pressure...
August 16, 2017: Physical Chemistry Chemical Physics: PCCP
Zhaoqiang Zheng, J D Yao, Bing Wang, G W Guo Wei Yang
Gas sensors play a vital role among a wide range of practical applications. Recently, propelled by the development of layered materials, gas sensors have gained much progress. However, the high operation temperature has restricted their further application. Herein, via a facile pulsed laser deposition (PLD) method, we demonstrate a flexible, transparent and high-performance gas sensor made of highly-crystalline indium selenide (In2Se3) film. Under UV-Vis-NIR light or even solar energy activation, the constructed gas sensors exhibit superior properties for detecting acetylene (C2H2) gas at room temperature...
July 31, 2017: Nanotechnology
Guido Ufer, Anke Gertzmann, Francisco Gasulla, Horst Röhrig, Dorothea Bartels
Phospholipase D (PLD) and its cleavage product phosphatidic acid (PA) are crucial in plant stress-signalling. Although some targets of PLD and PA have been identified, the signalling pathway is still enigmatic. This study demonstrates that the phosphoprotein At5g39570, now called PLD regulated protein1 (PLDrp1) from Arabidopsis thaliana is directly regulated by PLDα1. The protein PLDrp1 can be divided into two regions with distinct properties. The conserved N-terminal region specifically binds PA, while the repeat-rich C-terminal domain suggests interactions with RNAs...
July 29, 2017: Plant Journal: for Cell and Molecular Biology
Heather B Bradshaw, Emma Leishman
Classifications and characterizations of specific proteins, such as enzymes, not only allow us to understand biosynthetic and metabolic pathways but they also help to drive our understanding of protein structure and function. How those characterizations are evaluated, however, may change our interpretations and lead us into broader and novel directions in research. Here, we will make the argument that using lipidomics as a tool for characterizing enzymatic function over more traditional toolkit options allows for these types of revelations...
2017: Methods in Enzymology
J Maia, M Almada, A Silva, G Correia-da-Silva, N Teixeira, S I Sá, B M Fonseca
The endocannabinoid system (ECS) is involved in several physiological events that resulted in a growing interest in its modulation. Moreover, the uterine levels of anandamide (AEA), the major endocannabinoid, must be tightly regulated to create proper embryo implantation conditions. However, there are no evidences about the regulation of AEA in uterus by estrogen. Thus, the aim of this study is to elucidate whether estradiol benzoate (EB) and tamoxifen (TAM) administration to ovariectomized (OVX) rats can induce changes in the expression of cannabinoid receptors and AEA-metabolic enzymes in uterus by evaluating gene transcription and protein levels by qPCR, Western blot and immunohistochemistry...
July 22, 2017: Journal of Steroid Biochemistry and Molecular Biology
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