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https://www.readbyqxmd.com/read/28549259/purinergic-2x7-receptor-activation-regulates-wnt-signaling-in-human-mandibular-derived-osteoblasts
#1
Pimrumpai Rochanakit Sindhavajiva, Panunn Sastravaha, Mansuang Arksornnukit, Prasit Pavasant
OBJECTIVE: Purinergic 2X7 receptor (P2X7R) activation modulates in vitro mineralization by primary rat and human osteoblasts. However, the detailed mechanism of how P2X7R activation affects primary human osteoblasts remains unclear. The aim of this study was to investigate the effect of P2X7R activation on human mandibular-derived osteoblast (hMOB) differentiation. DESIGN: Primary human osteoblasts were obtained from non-pathologic mandibular bone from healthy patients...
May 18, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/28549064/chemomechanical-regulation-of-myosin-ic-cross-bridges-deducing-the-elastic-properties-of-an-ensemble-from-single-molecule-mechanisms
#2
Florian Berger, A J Hudspeth
Myosin Ic is thought to be the principal constituent of the motor that adjusts mechanical responsiveness during adaptation to prolonged stimuli by hair cells, the sensory receptors of the inner ear. In this context myosin molecules operate neither as filaments, as occurs in muscles, nor as single or few molecules, as characterizes intracellular transport. Instead, myosin Ic molecules occur in a complex cluster in which they may exhibit cooperative properties. To better understand the motor's remarkable function, we introduce a theoretical description of myosin Ic's chemomechanical cycle based on experimental data from recent single-molecule studies...
May 26, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28548864/oral-administration-of-a-medium-containing-both-d-aspartate-producing-live-bacteria-and-d-aspartate-reduces-rectal-temperature-in-chickens
#3
P H Do, P V Tran, M A Bahry, H Yang, G Han, A Tsuchiya, Y Asami, M Furuse, V S Chowdhury
1. The aim of this study was to investigate the effects on the rectal temperature of young chickens of the oral administration of a medium that contained both live bacteria that produce D-aspartate (D-Asp) and D-Asp. 2. In Experiment 1, chickens were subjected to chronic oral administration of either the medium (containing live bacteria and 2.46 μmol D-Asp) or water from 7 to 14 d of age. Plasma-free amino acids as well as mitochondrial biogenic gene expression in the breast muscle were analysed. In Experiment 2, 7-d-old chickens were subjected to acute oral administration of the above medium or of an equimolar amount of D-Asp to examine their effect on changes in rectal temperature...
May 26, 2017: British Poultry Science
https://www.readbyqxmd.com/read/28548825/nepetaefolins-a-j-cytotoxic-chinane-and-abietane-diterpenoids-from-caryopteris-nepetaefolia
#4
Cheng-Gang Zhang, Gui-Xin Chou, Xu-Dong Mao, Qing-Shan Yang, Jian-Li Zhou
Nepetaefolins A-J (1-10) and seven known compounds were isolated from the whole plant of Caryopteris nepetaefolia. The absolute configurations of 1-3 were determined from single-crystal X-ray diffraction and spectroscopic data. Compounds 6 and 7, with IC50 values of 6.3-9.0 μM, showed higher cytotoxicity than paclitaxel in one non-small-cell lung cancer, patient-derived xenograft (PDX) model when tested using PDX models and the adenosine triphosphate-tumor chemosensitivity assay (ATP-TCA).
May 26, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28548660/transcriptomic-and-micrornaomic-profiling-reveals-multi-faceted-mechanisms-to-cope-with-phosphate-stress-in-a-dinoflagellate
#5
Xinguo Shi, Xin Lin, Ling Li, Meizhen Li, Brian Palenik, Senjie Lin
Although gene regulation can occur at both transcriptional and epigenetic (microRNA) levels, combined transcriptomic and microRNAomic responses to environmental stress are still largely unexplored for marine plankton. Here, we conducted transcriptome and microRNAome sequencing for Prorocentrum donghaiense to understand the molecular mechanisms by which this dinoflagellate copes with phosphorus (P) deficiency. Under P-depleted conditions, G1/S specific cyclin gene was markedly downregulated, consistent with growth inhibition, and genes related to dissolved organic phosphorus (DOP) hydrolysis, carbon fixation, nitrate assimilation, glycolysis, and cellular motility were upregulated...
May 26, 2017: ISME Journal
https://www.readbyqxmd.com/read/28548451/molecular-and-functional-characterization-of-the-american-cockroach-periplaneta-americana-rab5-the-first-exopterygotan-low-molecular-weight-ovarian-gtpase-during-oogenesis
#6
Mohamed Elmogy, Amr A Mohamed, Muhammad Tufail, Tomohide Uno, Makio Takeda
The small Rab GTPases are key regulators of membrane vesicle trafficking. Ovaries of Periplaneta americana (Linnaeus) (Blattodea: Blattidae) have small molecular weight GTP/ATP-binding proteins during early and late vitellogenic periods of oogenesis. However, the identification and characterization of the detected proteins have not been yet reported. Herein, we cloned a cDNA encoding Rab5 from the American cockroach, P. americana, ovaries (PamRab5). It comprises 796 bp, encoding a protein of 213 amino acid residues with a predicted molecular weight of 23...
May 26, 2017: Insect Science
https://www.readbyqxmd.com/read/28548247/market-for-artemether-lumefantrine-to-treat-childhood-malaria-in-a-district-of-southern-mozambique
#7
Sergi Alonso, Khátia Munguambe, Elisa Sicuri
Malaria is one of the leading causes of death in sub-Saharan Africa. Artemisinin-based combination therapies are used as first-line treatment drugs, but their market is far from competitive. Market failures include limited availability, low quality, lack of information, and high costs of access. We estimated the theoretical demand for one of the most common artemisinin-based combination therapies, artemether-lumefantrine (AL), and its determinants among caregivers of children with malaria seeking care at public health facilities, thus, entitled to receive drugs for free, in southern Mozambique (year 2012)...
May 26, 2017: Health Economics
https://www.readbyqxmd.com/read/28547658/time-of-day-dependent-expression-of-purinergic-receptors-in-mouse-suprachiasmatic-nucleus
#8
Julian Lommen, Anna Stahr, Marc Ingenwerth, Amira A H Ali, Charlotte von Gall
Purinergic P2X and P2Y receptors are involved in mediating intercellular signalling via purines such as adenosine triphosphate (ATP). P2X and P2Y receptors have been implicated in numerous body functions including learning, memory and sleep. All of these body functions show time-of-day-dependent variations controlled by the master circadian oscillator located in the suprachiasmatic nucleus (SCN). Evidence exists for a role of purinergic signalling in intercellular coupling within SCN. However, few studies have been performed on the expression of purinergic receptors in SCN...
May 26, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28547528/manganese-ii-chloride-alters-nucleotide-and-nucleoside-catabolism-in-zebrafish-danio-rerio-adult-brain
#9
Stefani Altenhofen, Débora Dreher Nabinger, Talita Carneiro Brandão Pereira, Carlos Eduardo Leite, Maurício Reis Bogo, Carla Denise Bonan
ATP and adenosine, the main signaling molecules of purinergic system, are involved in toxicological effects induced by metals. The manganese (Mn) exposure induces several cellular changes, which could interfere with signaling pathways, such as the purinergic system. In this study, we evaluated the effects of exposure to manganese(II) chloride (MnCl2) during 96 h on nucleoside triphosphate diphosphohydrolase (NTPDase), ecto-5'-nucleotidase, and adenosine deaminase (ADA) activities, followed by analyzing the gene expression patterns of NTPDases (entpd1, entpd2a...
May 25, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28547381/purinergic-signalling-links-mechanical-breath-profile-and-alveolar-mechanics-with-the-pro-inflammatory-innate-immune-response-causing-ventilation-induced-lung-injury
#10
REVIEW
Djo Hasan, Paul Blankman, Gary F Nieman
Severe pulmonary infection or vigorous cyclic deformation of the alveolar epithelial type I (AT I) cells by mechanical ventilation leads to massive extracellular ATP release. High levels of extracellular ATP saturate the ATP hydrolysis enzymes CD39 and CD73 resulting in persistent high ATP levels despite the conversion to adenosine. Above a certain level, extracellular ATP molecules act as danger-associated molecular patterns (DAMPs) and activate the pro-inflammatory response of the innate immunity through purinergic receptors on the surface of the immune cells...
May 26, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28546431/disruption-of-mitochondrial-electron-transport-chain-function-potentiates-the-pro-apoptotic-effects-of-mapk-inhibition
#11
Andrew P Trotta, Jesse D Gelles, Madhavika N Serasinghe, Patrick Loi, Jack L Arbiser, Jerry E Chipuk
The mitochondrial network is a major site of ATP production through the coupled integration of the electron transport chain (ETC) with oxidative phosphorylation. In melanoma, arising from the Val600Glu mutation in the kinase v-RAF murine sarcoma viral oncogene homolog B (BRAFV600E), oncogenic signaling enhances glucose-dependent metabolism, while reducing mitochondrial ATP production. Likewise, when BRAFV600E is pharmacologically inhibited by targeted therapies (e.g. PLX-4032/Vemurafenib), glucose metabolism is reduced and cells increase mitochondrial ATP production to sustain survival...
May 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28546114/melaleuca-alternifolia-essential-oil-prevents-alterations-to-purinergic-enzymes-and-ameliorates-the-innate-immune-response-in-silver-catfish-infected-with-aeromonas-hydrophila
#12
Matheus D Baldissera, Carine F Souza, Pedro H Doleski, Agueda C de Vargas, Marta M M F Duarte, Thiago Duarte, Aline A Boligon, Daniela B R Leal, Bernardo Baldisserotto
Aeromonas hydrophila infection represents a major impediment to the development of aquaculture, leading to important economic losses. Over the last few years, different methods have been used to counteract and minimize the negative effects of this infection, such as the use of Melaleuca alternifolia essential oil, popularly known as tea tree oil (TTO), that possess a bactericide action against A. hydrophila. The purinergic system develops an important role in the inflammatory response, principally due to involvement of adenosine triphosphate (ATP) in the inflammatory process, as well as by the anti-inflammatory properties of adenosine (Ado), a molecule that is controlled by NTPDase, 5'-nucleotidase and adenosine deaminase (ADA) enzymes...
May 22, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28545374/modulators-of-the-efflux-pump-cdr1p-of-candida-albicans-mechanisms-of-action-and-chemical-features
#13
Viet-Khoa Tran-Nguyen, Rajendra Prasad, Pierre Falson, Ahcène Boumendjel
The multicomponent primary active ATP-binding cassette transporter Cdr1p in the structure of the pathogenic yeast Candida albicans is among the culprits of antifungal agent resistance reported in recent decades. So far, various potential novel inhibitors/ modulators of this protein have been purified, synthesized, and biologically tested, with results showing their ability to effectively reverse CaCdr1p-mediated drug resistance phenomenon. These compounds are of diverse origins, possess non-identical structural features and adopt different mechanisms of action...
May 22, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28544747/k-ras-mutation-and-amplification-status-is-predictive-of-resistance-and-high-basal-pakt-is-predictive-of-sensitivity-to-everolimus-in-biliary-tract-cancer-cell-lines
#14
Yvonne Yeung, David K Lau, Fiona Chionh, Hoanh Tran, Janson W T Tse, Andrew J Weickhardt, Mehrdad Nikfarjam, Andrew M Scott, Niall C Tebbutt, John M Mariadason
Advanced biliary tract cancer (BTC) has a poor prognosis and limited treatment options. The PI3K/Akt/mTOR signaling pathway is hyperactivated in a subset of BTCs and clinical activity to the mTOR inhibitor everolimus has been observed in some BTC patients. The goal of this study was to identify biomarkers predictive of everolimus response. Twenty BTC cell lines were assessed for everolimus sensitivity with a spectrum of growth inhibitory responses observed. Molecular biomarkers of sensitivity and resistance were identified by interrogation of the activation status of the Ras/MAPK and PI3K/Akt/mTOR pathways...
May 24, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28544649/activation-of-co2-by-vanadium-nitrogenase
#15
Nathaniel Sickerman, Yilin Hu, Markus Walter Ribbe
The reduction of CO2 into useful products, including hydrocarbon fuels, is an ongoing area of particular interest due to efforts to mitigate buildup of this greenhouse gas. While the industrial Fischer-Tropsch process can facilitate the hydrogenation of CO2 with H2 to form short-chain hydrocarbon products under high temperatures and pressures, a desire to perform these reactions under ambient conditions has inspired the use of biological approaches. Particularly, enzymes offer insight into how to activate and reduce CO2, but only one enzyme, nitrogenase, can perform the multielectron, multiproton reduction of CO¬2 into hydrocarbons...
May 22, 2017: Chemistry, An Asian Journal
https://www.readbyqxmd.com/read/28544624/pyrimidine-containing-epidermal-growth-factor-receptor-kinase-inhibitors-synthesis-and-biological-evaluation
#16
Gaurav Joshi, Himanshu Nayyar, Sourav Kalra, Praveen Sharma, Anjana Munshi, Sandeep Singh, Raj Kumar
Structure based design and synthesis of pyrimidine containing reversible epidermal growth factor receptor (EGFR) inhibitors 1a-d are reported. The compounds (1a-d) inhibited the EGFR kinase activity in vitro with IC50 range 740 nM to 3 μM. mRNA expression of EGFR downstream target genes i.e. twist, c-fos and aurora were found to be altered upon treatment with compounds 1a-d. The compounds 1a-d exhibited excellent anticancer activity at low micromolar level (3.2-9 μM) in lung, colon and breast cancer cell lines...
May 23, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28544603/metabolic-reprogramming-of-macrophages-exposed-to-silk-poly-lactic-co-glycolic-acid-and-silica-nanoparticles
#17
Raquel Saborano, Thidarat Wongpinyochit, John D Totten, Blair F Johnston, F Philipp Seib, Iola F Duarte
Monitoring macrophage metabolism in response to nanoparticle exposure provides new insights into biological outcomes, such as inflammation or toxicity, and supports the design of tailored nanomedicines. This paper describes the metabolic signature of macrophages exposed to nanoparticles ranging in diameter from 100 to 125 nm and made from silk, poly(lactic-co-glycolic acid) or silica. Nanoparticles of this size and type are currently at various stages of preclinical and clinical development for drug delivery applications...
May 8, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28544567/chemoproteomics-aided-medicinal-chemistry-for-the-discovery-of-epha2-inhibitors
#18
Stephanie Heinzlmeir, Jonas Lohse, Tobias Treiber, Denis Kudlinzki, Verena Linhard, Santosh Lakshmi Gande, Sridhar Sreeramulu, Krishna Saxena, Xiaofeng Liu, Mathias Wilhelm, Harald Schwalbe, Bernhard Kuster, Guillaume Médard
The receptor tyrosine kinase EPHA2 has gained interest as therapeutic drug target in cancer and infectious diseases. However, EPHA2 research and EPHA2-based therapies have been hampered by the lack of selective small molecule inhibitors. Here, we report on the synthesis and evaluation of dedicated EPHA2 inhibitors based on the clinical BCR-ABL/SRC inhibitor Dasatinib as a lead structure. We designed hybrid structures of Dasatinib and the previously known EPHA2 binders CHEMBL249097, PD-173955 and a known EPHB4 inhibitor in order to exploit both the ATP pocket entrance as well as the ribose pocket as binding epitopes in the kinase EPHA2...
May 24, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28544552/kinome-wide-profiling-prediction-of-small-molecules
#19
Frieda Anna Sorgenfrei, Simone Fulle, Benjamin Merget
Extensive kinase profiling data, covering more than half of the human kinome, are nowadays available and allow construction of activity prediction models of high practical use. Proteochemometric (PCM) approaches utilize compound and protein descriptors, which enables the extrapolation of bioactivity values also to so far unexplored kinases. In this study, the potential of PCM to make large-scale predictions on the entire kinome is explored, considering the applicability on novel compounds and kinases, including clinically relevant mutants...
May 23, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28544208/ultra-high-field-magnetic-resonance-spectroscopy-in-non-alcoholic-fatty-liver-disease-novel-mechanistic-and-diagnostic-insights-of-energy-metabolism-in-non-alcoholic-steatohepatitis-and-advanced-fibrosis
#20
Stefan Traussnigg, Christian Kienbacher, Martin Gajdošík, Ladislav Valkovič, Emina Halilbasic, Judith Stift, Christian Rechling, Harald Hofer, Petra Steindl-Munda, Peter Ferenci, Fritz Wrba, Siegfried Trattnig, Martin Krššák, Michael Trauner
BACKGROUND & AIMS: With the rising prevalence of non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) non-invasive tools obtaining pathomechanistic insights to improve risk stratification are urgently needed. We therefore explored high- and ultra-high-field magnetic resonance spectroscopy (MRS) to obtain novel mechanistic and diagnostic insights into alterations of hepatic lipid, cell membrane and energy metabolism across the spectrum of NAFLD. METHODS: MRS and liver biopsy were performed in 30 NAFLD patients with NAFL (n=8) or NASH (n=22)...
April 24, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
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