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Jingjing Wu, Mingzhi Zhang, Delong Liu
The Bruton tyrosine kinase (BTK) inhibitor, ibrutinib, has been approved for the treatment of chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrom's macroglobulinemia. Acquired resistance to ibrutinib due to BTK C481S mutation has been reported. Mutations in PLCγ2 can also mediate resistance to ibrutinib. Untoward effects due to off-target effects are also disadvantages of ibrutinib. More selective and potent BTK inhibitors (ACP-196, ONO/GS-4059, BGB-3111, CC-292) are being investigated. This review summarized the preclinical research and clinical data of ONO/GS-4059...
October 20, 2016: Oncotarget
Bharathkumar Inturi, Gurubasavaraj V Pujar, Madhusudhan N Purohit
Mycobacterium tuberculosis enoyl-ACP reductase (InhA) has been validated as a promising target for antitubercular agents. Isoniazid (INH), the most prescribed drug to treat tuberculosis (TB), inhibits a NADH-dependent InhA that provides precursors of mycolic acids, which are components of the mycobacterial cell wall. It is a pro-drug that needs activation to form the inhibitory INH-NAD adduct by KatG coding for catalase-peroxidase. The INH resistance of M. tuberculosis is caused by mutations in KatG, which may lead to multidrug-resistant TB (MDR-TB)...
October 24, 2016: Archiv der Pharmazie
Xufeng Niu, Siqian Chen, Feng Tian, Lizhen Wang, Qingling Feng, Yubo Fan
The aim of this study is to investigate the calcium and orthophosphate ions release during the transformation of amorphous calcium phosphate (ACP) to hydroxyapatite (HA) in aqueous solution. The ACP is prepared by a wet chemical method and further immersed in the distilled water for various time points till 14d. The release of calcium and orthophosphate ions is measured with calcium and phosphate colorimetric assay kits, respectively. The transition of ACP towards HA is detected by x-ray diffraction (XRD), transmission electron microscopy (TEM), and fourier transform infrared spectroscopy (FTIR)...
January 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
Weidan Na, Qing Liu, Bowen Sui, Tianyu Hu, Xingguang Su
A novel and effective fluorescence strategy was developed for sensitive and selective detection of acid phosphatase (ACP). A förster resonance energy transfer (FRET) biosensor was established by attaching nile red (NR) to graphene quantum dots (GQDs) via lecithin/β-Cyclodextrin (lecithin/β-CD) complex as the linker. The introduction of lecithin/β-CD would brought GQDs-NR pair close enough through both electrostatic interaction and hydrophobic interaction, thereby making the FRET occur and thus resulting in the fluorescence quenching of GQDs (donor) and meanwhile the fluorescence enhancement of NR (acceptor)...
December 1, 2016: Talanta
Devon E Anderson, Brandon D Markway, Derek Bond, Helen E McCarthy, Brian Johnstone
BACKGROUND: Lowering oxygen from atmospheric level (hyperoxia) to the physiological level (physioxia) of articular cartilage promotes mesenchymal stem cell (MSC) chondrogenesis. However, the literature is equivocal regarding the benefits of physioxic culture on preventing hypertrophy of MSC-derived chondrocytes. Articular cartilage progenitors (ACPs) undergo chondrogenic differentiation with reduced hypertrophy marker expression in hyperoxia but have not been studied in physioxia. This study sought to delineate the effects of physioxic culture on both cell types undergoing chondrogenesis...
October 20, 2016: Stem Cell Research & Therapy
Tina L Mistry, Lena Truong, Arun K Ghosh, Michael E Johnson, Shahila Mehboob
The enoyl-ACP reductase (FabI) enzyme is a well validated target for anti-staphylococcal drug discovery and development. With the goal of finding alternate therapeutics for drug resistant strains of S. aureus, such as methicillin resistant S. aureus (MRSA), our previously published series of benzimidazole-based inhibitors of the FabI enzyme from F. tularensis (FtFabI) have been evaluated against FabI from S. aureus (SaFabI). We report here the preliminary structure-activity relationship of this series and the prioritization of compounds toward lead optimization...
October 18, 2016: ACS Infectious Diseases
Shohei Hayashi, Yasuharu Satoh, Tetsuro Ujihara, Yusuke Takata, Tohru Dairi
In some microorganisms, polyunsaturated fatty acids (PUFAs) are biosynthesized by PUFA synthases characterized by tandem acyl carrier proteins (ACPs) in subunit A. These ACPs were previously shown to be important for PUFA productivity. In this study, we examined their function in more detail. PUFA productivities increased depending on the number of ACPs without profile changes in each subunit A of eukaryotic and prokaryotic PUFA synthases. We also constructed derivative enzymes from subunit A with 5 × ACPs...
October 18, 2016: Scientific Reports
Traci M Kazmerski, Daniel J Weiner, Janice Matisko, Diane Schachner, Whitney Lerch, Carol May, Scott H Maurer
INTRODUCTION: Advance care planning (ACP), though recommended, has not been studied in adolescents with cystic fibrosis (CF). This quality improvement project engaged adolescents with advanced CF disease in ACP and assessed patient and CF provider attitudes and preferences regarding ACP discussions and tools. MATERIALS AND METHODS: Patients ≤22 years with advanced CF (FEV1 ≤40% predicted, >2 pulmonary exacerbations requiring IV antibiotics in 1 year, and/or use of home oxygen or non-invasive ventilation) were referred to the pediatric palliative care team (PC)...
October 17, 2016: Pediatric Pulmonology
Yong Li, Xu Wang, Jie Yang, Xilei Xie, Mengmeng Li, Jinye Niu, Lili Tong, Bo Tang
Carbon monoxide (CO), a crucial gas message molecule, plays an important role in the regulation of physiological and pathological process. Hypoxia-induced CO is involved in modulating various cellular activities, including signal transduction, proliferation, and apoptosis. However, tracking CO fluctuation in the hypoxic cells is still a challenge due to lack of straight forward, visualized and non-invasive tools. In this work, based on metal palladium-catalyzed reaction, we present the rational design, synthesis and biological utility of an azobenzene-cyclopalladium-based fluorescent probe, ACP-2, for CO monitoring...
October 17, 2016: Analytical Chemistry
Xavier Freixa, Laura Llull, Sameer Gafoor, Ignacio Cruz-Gonzalez, Samera Shakir, Heyder Omran, Sergio Berti, Gennaro Santoro, Joelle Kefer, Ulf Landmesser, Jens Erik Nielsen-Kudsk, Prapa Kanagaratnam, Fabian Nietlispach, Steffen Gloekler, Adel Aminian, Paolo Danna, Marco Rezzaghi, Friederike Stock, Miroslava Stolcova, Luis Paiva, Marco Costa, Xavier Millán, Reda Ibrahim, Tobias Tichelbäcker, Wolfgang Schillinger, Jai-Wun Park, Horst Sievert, Bernhard Meier, Apostolos Tzikas
Cardioembolic strokes are generally more lethal and disabling than other source of strokes. Data from PROTECT AF (Watchman Left Atrial Appendage Closure Technology for Embolic Protection in Patients With Atrial Fibrillation) suggest that strokes after left atrial appendage occlusion (LAAO) with the Watchman device are less disabling than those in the warfarin group. No data assessing the severity of strokes after LAAO with the AMPLATZER Cardiac Plug (ACP) are available. The objective of the study was to evaluate the severity of cerebrovascular events after LAAO with the ACP in a population mostly characterized by an absolute or relative contraindication to oral anticoagulation...
September 15, 2016: American Journal of Cardiology
Zhenle Yang, Hongying Ji, Dantong Liu
Cyperus esculentus is unique in that it can accumulate rich oil in tuber. However, the underlying mechanism of tuber oil biosynthesis is still unclear. Our transcriptional analyses of the pathways from pyruvate production up to triacylglycerol (TAG) accumulation in tuber revealed many distinct species-specific lipid expression patterns from oil seeds and fruits, indicating that in C. esculentus tuber, (1) carbon flux from sucrose toward plastid pyruvate could be produced mostly through cytosolic glycolytic pathway, (2) acetyl-CoA synthetase might be an important contributor to acetyl-CoA formation for plastid fatty acid biosynthesis, (3) expression pattern for stearoyl-ACP desaturase was associated with high oleic acid composition, (4) it was most likely that endoplasmic reticulum-associated acyl-CoA synthetase played a significant role in the export of fatty acids between the plastid and ER, (5) lipid phosphate phosphatase (LPP)-δ was most probably related to the formation of DAG pool in Kennedy pathway, (6) diacylglyceroltransacylase 2 (DGAT2) and phospholipid:diacylglycerolacyltransferase 1 (PDAT1) might play crucial roles in tuber oil biosynthesis...
October 13, 2016: Plant & Cell Physiology
J Tyler Youngquist, Travis C Korosh, Brian F Pfleger
Free fatty acids (FFA) are an attractive platform chemical that serves as a functional intermediate in metabolic pathways for producing oleochemicals. Many groups have established strains of Escherichia coli capable of producing various chain-length mixtures of FFA by heterologous expression of acyl-ACP thioesterases. For example, high levels of dodecanoic acid are produced by an E. coli strain expressing the Umbellularia californica FatB2 thioesterase, BTE. Prior studies achieved high dodecanoic acid yields and productivities under phosphate-limiting media conditions...
October 13, 2016: Journal of Industrial Microbiology & Biotechnology
Jiangwei Yao, Megan E Ericson, Matthew W Frank, Charles O Rock
Enoyl-acyl carrier protein reductase catalyzes the last step in each elongation cycle of type II bacterial fatty acid synthesis and is a key regulatory protein in bacterial fatty acid synthesis. The facultative intracellular pathogen Listeria monocytogenes encodes two functional enoyl-ACP isoforms based on their ability to complement the temperature-sensitive growth phenotype of E. coli strain JP1111 (fabI(Ts)). The FabI isoform was inactivated by the FabI selective inhibitor AFN-1252, but the FabK isoform was not affected by the drug as expected...
October 10, 2016: Infection and Immunity
Andrew G Nicholson, Frank Detterbeck, Alexander Marx, Anja C Roden, Alberto M Marchevsky, Kiyoshi Mukai, Gang Chen, Mirella Marino, Michael A den Bakker, Woo-Ick Yang, Meagan Judge, Lynn Hirschowitz
AIMS: The International Collaboration on Cancer Reporting (ICCR) is a not-for-profit organisation formed by the Royal Colleges of Pathologists of Australasia and the United Kingdom, the College of American Pathologists, the Canadian Association of Pathologists-Association Canadienne des Pathologists (CAP-ACP) in association with the Canadian Partnership Against Cancer (CPAC), and the European Society of Pathology (ESP). Its goal is to produce standardised, internationally agreed, evidence-based datasets for use throughout the world...
October 13, 2016: Histopathology
Grigoriy E Gurvits, Gloria Lan, Amy Tan, Arlene Weissman
BACKGROUND: Increasing prevalence of inflammatory bowel disease (IBD) poses significant challenges to medical community. Preventive medicine, including vaccination against opportunistic infections, is important in decreasing morbidity and mortality in patients with IBD. We conduct first study to evaluate general awareness and adherence to immunisation guidelines by primary care physicians in the USA. METHODS: We administered an electronic questionnaire to the research panel of the American College of Physicians (ACP) assessing current vaccination practices, barriers to vaccination and provider responsibility for administering vaccinations and compared responses with the European Crohn's and Colitis Organization consensus guidelines and expert opinion from the USA...
October 12, 2016: Postgraduate Medical Journal
Yong Wang
We design an axiomatization for reversible computation called reversible ACP (RACP). It has four extendible modules: basic reversible processes algebra, algebra of reversible communicating processes, recursion and abstraction. Just like process algebra ACP in classical computing, RACP can be treated as an axiomatization foundation for reversible computation.
2016: SpringerPlus
Meredith A Skiba, Andrew P Sikkema, William D Fiers, William H Gerwick, David H Sherman, Courtney C Aldrich, Janet L Smith
Polyketide metabolites produced by modular type I polyketide synthases (PKS) acquire their chemical diversity through the variety of catalytic domains within modules of the pathway. Methyltransferases are among the least characterized of the catalytic domains common to PKS systems. We determined the domain boundaries and characterized the activity of a PKS C-methyltransferase (C-MT) from the curacin A biosynthetic pathway. The C-MT catalyzes S-adenosylmethionine-dependent methyl transfer to the α-position of β-ketoacyl substrates linked to acyl carrier protein (ACP) or a small-molecule analog, but does not act on β-hydroxyacyl substrates or malonyl-ACP...
October 10, 2016: ACS Chemical Biology
Yingjia Han, Gen Xu, Hewei Du, Jieyun Hu, Zhanji Liu, Hui Li, Jiansheng Li, Xiaohong Yang
We identified 11 SAD genes, and mined their natural variations associated with the conservation of stearic to oleic acid, especially ZmSAD1 supported by both the QTL and an expression QTL. Maize oil is generally regarded as a healthy vegetable oil owing to its low abundance of saturated fatty acids. Stearoyl-ACP desaturase (SAD) is a key rate-limiting enzyme for the conservation of stearic (C18:0) to oleic (C18:1) acid. Here, 11 maize SAD genes were identified to have more divergent functions than Arabidopsis SAD genes...
October 7, 2016: TAG. Theoretical and Applied Genetics. Theoretische und Angewandte Genetik
Frank J Byrne, Matthew P Daugherty, Elizabeth E Grafton-Cardwell, James A Bethke, Joseph G Morse
BACKGROUND: Studies were conducted to evaluate uptake and retention of 3 systemic neonicotinoid insecticides, dinotefuran, imidacloprid, and thiamethoxam, in potted citrus nursery plants treated at standard label rates. Infestation of these plants placed at a field site with moderate levels of Asian citrus psyllid (ACP) was monitored for 14 weeks following treatments and insecticide residues in leaf tissue were quantified using ELISA. Bioassays were conducted using leaves harvested on various dates post-treatment to compare the efficacies of residues against adult ACP...
October 7, 2016: Pest Management Science
Anat Akiva, Michael Kerschnitzki, Iddo Pinkas, Wolfgang Wagermaier, Karina Yaniv, Peter Fratzl, Lia Addadi, Steve Weiner
Both in vivo and ex vivo observations support the hypothesis that bone mineral formation proceeds via disordered precursor phases. The characteristics of the precursor phases are however not well defined, but OCP-like, ACP-like and HPO42- enriched phases were detected. Here we use in vivo Raman spectroscopy and high-resolution wide-angle X-ray diffraction (WAXD) to characterize and map at 2µm resolution the mineral phases in the rapidly forming tail fin bones of living zebrafish larvae and zebrafish larvae immediately after sacrifice, respectively...
October 6, 2016: Journal of the American Chemical Society
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