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https://www.readbyqxmd.com/read/28727444/fosfomycin-biosynthesis-via-transient-cytidylylation-of-2-hydroxyethylphosphonate-by-the-bifunctional-fom1-enzyme
#1
Su-Hee Cho, Seung-Young Kim, Takeo Tomita, Taro Shiraishi, Jin-Soo Park, Shusuke Sato, Fumitaka Kudo, Tadashi Eguchi, Nobutaka Funa, Makoto Nishiyama, Tomohisa Kuzuyama
Fosfomycin is a wide-spectrum phosphonate antibiotic that is used clinically to treat cystitis, tympanitis, etc. Its biosynthesis starts with the formation of a carbon-phosphorus bond catalyzed by the phosphoenolpyruvate phosphomutase Fom1. We identified an additional cytidylyltransferase (CyTase) domain at the Fom1 N-terminus in addition to the phosphoenolpyruvate phosphomutase domain at the Fom1 C-terminus. Here, we demonstrate that Fom1 is bifunctional and that the Fom1 CyTase domain catalyzes the cytidylylation of the 2-hydroxyethylphosphonate (HEP) intermediate to produce cytidylyl-HEP...
July 20, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28720432/adhesion-and-invasion-of-clostridium-perfringens-type-a-into-epithelial-cells
#2
Luis A Llanco, Viviane Nakano, Claudia T P de Moraes, Roxane M F Piazza, Mario J Avila-Campos
Clostridium perfringens is the causative agent for necrotic enteritis. It secretes the major virulence factors, and α- and NetB-toxins that are responsible for intestinal lesions. The TpeL toxin affects cell morphology by producing myonecrosis, but its role in the pathogenesis of necrotic enteritis is unclear. In this study, the presence of netB and tpeL genes in C. perfringens type A strains isolated from chickens with necrotic enteritis, their cytotoxic effects and role in adhesion and invasion of epithelial cells were evaluated...
July 7, 2017: Brazilian Journal of Microbiology: [publication of the Brazilian Society for Microbiology]
https://www.readbyqxmd.com/read/28706487/pekinenin-e-inhibits-the-growth-of-hepatocellular-carcinoma-by-promoting-endoplasmic-reticulum-stress-mediated-cell-death
#3
Lu Fan, Qingling Xiao, Yanyan Chen, Gang Chen, Jinao Duan, Weiwei Tao
Hepatocellular carcinoma (HCC) is a malignant primary liver cancer with poor prognosis. In the present study, we report that pekinenin E (PE), a casbane diterpenoid derived from the roots of Euphorbia pekinensis, has a strong antitumor activity against human HCC cells both in vitro and in vivo. PE suppressed the growth of human HCC cells Hep G2 and SMMC-7721. In addition, PE-mediated endoplasmic reticulum (ER) stress caused increasing expressions of C/EBP homologous protein (CHOP), leading to apoptosis in HCC cells both in vitro and in vivo...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28701716/glyat-regulates-jnk-mediated-cell-death-in-drosophila
#4
Pu Ren, Wenzhe Li, Lei Xue
Cell death is a fundamental progress that regulates cell number, tissue homeostasis and organ size in development. The c-Jun N-terminal kinase (JNK) pathway has been evolutionarily conserved from fly to human, and plays essential roles in regulating cell death. To characterize additional genes that regulate JNK signaling, we performed a genetic screen in Drosophila and identified dGLYAT, a novel gene whose function was previously unknown, as a modulator of JNK-mediated cell death. We found that loss of dGLYAT suppressed JNK activation and cell death triggered by over-expression of Egr or Hep, or depletion of puc or lgl in development, suggesting dGLYAT regulates both ectopic and physiological functions of JNK pathway...
July 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28689856/restrictions-on-access-to-direct-acting-antivirals-for-people-who-inject-drugs-the-european-hep-core-study-and-the-role-of-patient-groups-in-monitoring-national-hcv-responses
#5
J V Lazarus, K Safreed-Harmon, S R Stumo, M Jauffret-Roustide, M Maticic, T Reic, E Schatz, J Tallada, M Harris
In 2016, the World Health Organization (WHO) called for the elimination of viral hepatitis as a public health threat and established the targets of achieving an 80% reduction in new infections and a 65% reduction in deaths from the hepatitis C virus (HCV) by 2030. If European countries are to come close to reaching the WHO targets, they must squarely address the HCV prevention, testing and treatment needs of people who inject drugs (PWID). This viewpoint reports on findings from the 2016 European Hep-CORE study, which was unique in its utilisation of patient groups as a source of hepatitis policy information...
July 6, 2017: International Journal on Drug Policy
https://www.readbyqxmd.com/read/28684446/persistence-of-exhaustion-in-cured-hep-c
#6
David E Kaplan
No abstract text is available yet for this article.
July 6, 2017: Blood
https://www.readbyqxmd.com/read/28678963/scientometric-indicators-for-brazilian-research-on-high-energy-physics-1983-2013
#7
Gonzalo R Alvarez, Samile A S Vanz, Marcia C Barbosa
This article presents an analysis of Brazilian research on High Energy Physics (HEP) indexed by Web of Science (WoS) from 1983 to 2013. Scientometric indicators for output, collaboration and impact were used to characterize the field under study. The results show that the Brazilian articles account for 3% of total HEP research worldwide and that the sharp rise in the scientific activity between 2009 and 2013 may have resulted from the consolidation of graduate programs, the increase of the funding and of the international collaboration as well as the implementation of the Rede Nacional de Física de Altas Energias (RENAFAE) in 2008...
June 29, 2017: Anais da Academia Brasileira de Ciências
https://www.readbyqxmd.com/read/28678474/methylcobalamin-dependent-radical-sam-c-methyltransferase-fom3-recognizes-cytidylyl-2-hydroxyethylphosphonate-and-catalyzes-the-nonstereoselective-c-methylation-in-fosfomycin-biosynthesis
#8
Shusuke Sato, Fumitaka Kudo, Seung-Young Kim, Tomohisa Kuzuyama, Tadashi Eguchi
A methylcobalamin (MeCbl)-dependent radical S-adenosyl-l-methionine (SAM) methyltransferase Fom3 was found to catalyze the C-methylation of cytidylyl-2-hydroxyethylphosphonate (HEP-CMP) to give cytidylyl-2-hydroxypropylphosphonate (HPP-CMP), although it was originally proposed to catalyze the C-methylation of 2-hydroxyethylphosphonate to give 2-hydroxypropylphosphonate in the biosynthesis of a unique C-P bond containing antibiotic fosfomycin in Streptomyces. Unexpectedly, the Fom3 reaction product from HEP-CMP was almost a 1:1 diastereomeric mixture of HPP-CMP, indicating that the C-methylation is not stereoselective...
July 7, 2017: Biochemistry
https://www.readbyqxmd.com/read/28672193/quantitative-differentiation-of-multiple-virus-in-blood-using-nanoporous-silicon-oxide-immunosensor-and-artificial-neural-network
#9
W Chakraborty, R Ray, N Samanta, C RoyChaudhuri
In spite of the rapid developments in various nanosensor technologies, it still remains challenging to realize a reliable ultrasensitive electrical biosensing platform which will be able to detect multiple viruses in blood simultaneously with a fairly high reproducibility without using secondary labels. In this paper, we have reported quantitative differentiation of Hep-B and Hep-C viruses in blood using nanoporous silicon oxide immunosensor array and artificial neural network (ANN). The peak frequency output (fp) from the steady state sensitivity characteristics and the first cut off frequency (fc) from the transient characteristics have been considered as inputs to the multilayer ANN...
June 24, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28662680/systematic-review-of-patient-reported-quality-of-life-following-stereotactic-ablative-radiotherapy-for-primary-and-metastatic-liver-cancer
#10
REVIEW
Adam Mutsaers, Jeffrey Greenspoon, Cindy Walker-Dilks, Anand Swaminath
BACKGROUND: Stereotactic ablative radiotherapy (SABR) is a safe and effective modality in patients with liver cancer who are ineligible for other local therapies. However SABR is not current standard of practice and requires further validation. Patient reported quality of life (QOL) is key to this validation, yet no systematic reviews to date have been performed to analyse QOL following liver SABR. QOL is a critical part of therapy evaluation, particularly in disease states with short life expectancy...
June 29, 2017: Radiation Oncology
https://www.readbyqxmd.com/read/28652242/preclinical-characterization-of-the-inhaled-small-molecule-respiratory-syncytial-virus-l-protein-polymerase-inhibitor-pc786
#11
Matthew Coates, Daniel Brookes, Young-In Kim, Heather Allen, Euan A F Fordyce, Elizabeth A Meals, Thomas Colley, Claire-Lise Ciana, Guillaume F Parra, Vladimir Sherbukhin, Jennifer A Stockwell, Jennifer C Thomas, S Fraser Hunt, Lauren Anderson-Dring, Stuart T Onions, Lindsey Cass, Peter J Murray, Kazuhiro Ito, Pete Strong, John P Devincenzo, Garth Rapeport
Although respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in infants and young children, attempts to develop an effective therapy have so far proved unsuccessful. Herein we report the preclinical profiles of PC786, a potent non-nucleoside RSV L-protein polymerase inhibitor, designed for inhalation treatment of RSV infection. PC786 demonstrated a potent and selective anti-viral activity against laboratory adapted or clinical isolates of RSVA (IC50: <0.09 - 0...
June 26, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28650400/high-need-to-switch-cart-or-co-medication-with-the-initiation-of-daas-in-elderly-hiv-hcv-co-infected-patients
#12
Elise J Smolders, Colette Smit, Clara Tmm De Kanter, Anton Dofferhoff, Joop E Arends, Kees Brinkman, Bart Rijnders, Marc Van Der Valk, Peter Reiss, David M Burger
BACKGROUD: To describe the use of non-antiretroviral co-medication and combination antiretroviral therapy (cART) in HIV/hepatitis C virus (HCV) co-infected patients, and to predict the potential for drug-drug interactions (DDIs) with direct-acting antivirals (DAAs) against HCV. METHODS: This is a retrospective, cross-sectional study, using the Dutch nationwide ATHENA observational HIV cohort database. All patients with a known HIV/HCV co-infection on 1 January 2015 were included...
June 22, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28640349/use-of-gc-ms-to-identify-chemical-constituents-and-cytotoxic-activity-of-the-leaves-of-phoradendron-mucronatum-and-phoradendron-microphyllum-viscaceae
#13
Isla V G A Bastos, Tatiane B DE Oliveira, Maria D Rodrigues, Gardênia C G Militão, Teresinha G DA Silva, Izabel C C Turatti, Norberto P Lopes, Sebastião J DE Melo
Phoradendron mucronatum and P. microphyllum are plants that found in tropical and subtropical areas, used in traditional medicine and popularly known as mistle-thrush. The aim of this study was to identify the chemical constituents of different leaf extracts from P. mucronatum and P. microphyllum and assess cytotoxic activity against strains from a human tumour cells. Extracts obtained with hexane, dichloromethane, chloroform and ethyl acetate from the leaves were analysed by gas chromatography coupled with mass spectrometry (GC-MS) and the cytotoxicity was assessed by the MTT method (bromide (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide))...
April 2017: Anais da Academia Brasileira de Ciências
https://www.readbyqxmd.com/read/28630303/how-members-of-the-human-gut-microbiota-overcome-the-sulfation-problem-posed-by-glycosaminoglycans
#14
Alan Cartmell, Elisabeth C Lowe, Arnaud Baslé, Susan J Firbank, Didier A Ndeh, Heath Murray, Nicolas Terrapon, Vincent Lombard, Bernard Henrissat, Jeremy E Turnbull, Mirjam Czjzek, Harry J Gilbert, David N Bolam
The human microbiota, which plays an important role in health and disease, uses complex carbohydrates as a major source of nutrients. Utilization hierarchy indicates that the host glycosaminoglycans heparin (Hep) and heparan sulfate (HS) are high-priority carbohydrates for Bacteroides thetaiotaomicron, a prominent member of the human microbiota. The sulfation patterns of these glycosaminoglycans are highly variable, which presents a significant enzymatic challenge to the polysaccharide lyases and sulfatases that mediate degradation...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28615927/p-tsa-promoted-syntheses-of-5h-benzo-h-thiazolo-2-3-b-quinazoline-and-indeno-1-2-d-thiazolo-3-2-a-pyrimidine-analogs-molecular-modeling-and-in-vitro-antitumor-activity-against-hepatocellular-carcinoma
#15
Amit K Keshari, Ashok K Singh, Vinit Raj, Amit Rai, Prakruti Trivedi, Balaram Ghosh, Umesh Kumar, Atul Rawat, Dinesh Kumar, Sudipta Saha
In our efforts to address the rising incidence of hepatocellular carcinoma (HCC), we have made a commitment to the synthesis of novel molecules to combat Hep-G2 cells. A facile and highly efficient one-pot, multicomponent reaction has been successfully devised utilizing a p-toluenesulfonic acid (p-TSA)-catalyzed domino Knoevenagel/Michael/intramolecular cyclization approach for the synthesis of novel 5H-benzo[h]thiazolo[2,3-b]quinazoline and indeno[1,2-d] thiazolo[3,2-a]pyrimidine analogs bearing a bridgehead nitrogen atom...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28612519/glucosyltransferase-dependent-and-independent-effects-of-tcdb-on-the-proteome-of-hep-2-cells
#16
Jelena Erdmann, Johannes Junemann, Anke Schröder, Ingo Just, Ralf Gerhard, Andreas Pich
Toxin B (TcdB) of the nosocomial pathogen C. difficile has been reported to exhibit a glucosyltransferase dependent and independent effect on treated HEp-2 cells at toxin concentration above 0.3 nM. In order to investigate and further characterize both effects epithelial cells were treated with wild type TcdB and glucosyltransferase-deficient TcdBNXN and their proteomes were analyzed by LC-MS. Triplex SILAC labeling was used for quantification. Identification of 5212 and quantification of 4712 protein groups was achieved...
June 14, 2017: Proteomics
https://www.readbyqxmd.com/read/28570910/the-impact-of-anticancer-activity-upon-beta-vulgaris-extract-mediated-biosynthesized-silver-nanoparticles-ag-nps-against-human-breast-mcf-7-lung-a549-and-pharynx-hep-2-cancer-cell-lines
#17
K Venugopal, H Ahmad, E Manikandan, K Thanigai Arul, K Kavitha, M K Moodley, K Rajagopal, R Balabhaskar, M Bhaskar
The present study tried for a phyto-synthetic method of producing silver nanoparticles (Ag-NPs) with size controlled as and eco-friendly route that can lead to their advanced production with decorative tranquil morphology. By inducing temperature fluctuation of the reaction mixture from 25 to 80°C the plasmon resonance band raised slowly which had an ultimate effect on size and shape of Ag-NPs as shown by UV-visible spectroscopy and TEM results. The biosynthesized nanoparticles showed good cytotoxic impact against MCF-7, A549 and Hep2 cells compared to normal cell lines...
May 24, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/28552598/synthesis-and-in-vitro-antiproliferative-evaluation-of-pegylated-triterpene-acids
#18
Marta Medina-O'Donnell, Francisco Rivas, Fernando J Reyes-Zurita, Antonio Martinez, Francisco Galisteo-González, Jose A Lupiañez, Andres Parra
A set of PEGylated derivatives of oleanolic and maslinic acids has been semi-synthesised, attaching ethylene glycol, diethylene glycol, triethylene glycol or tetraethylene glycol to the C-28 carboxyl group of these natural triterpenes and some derivatives. Another set of PEGylated derivatives has been semi-synthesised by connecting the same four ethylene glycols to the hydroxyl groups of the A ring of these triterpenic acids, through a carbonate linker, by reaction with trichloromethyl chloroformate. The aqueous solubility of some of these PEGylated derivatives has been compared with that of maslinic acid...
May 25, 2017: Fitoterapia
https://www.readbyqxmd.com/read/28512032/cytotoxic-triterpene-diglycosides-from-the-sea-cucumber-stichopus-horrens
#19
Nguyen Xuan Cuong, Le Thi Vien, Le Hoang, Tran Thi Hong Hanh, Do Thi Thao, Nguyen Van Thanh, Nguyen Hoai Nam, Do Cong Thung, Phan Van Kiem, Chau Van Minh
Using various chromatographic separation techniques, eight triterpene diglycosides (1-8), including four new compounds namely stichorrenosides A-D (1-4), were isolated from a methanol extract of the Vietnamese sea cucumber S. horrens. Their structures were elucidated based on spectroscopic analyses, including HR ESI MS, 1D and 2D NMR. Their in vitro cytotoxic activity against five human cancer cell lines, Hep-G2 (hepatoma cancer), KB (epidermoid carcinoma), LNCaP (prostate cancer), MCF7 (breast cancer), and SK-Mel2 (melanoma), was evaluated using SRB methods...
May 6, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28505596/engineered-hydrogels-increase-the-post-transplantation-survival-of-encapsulated-hesc-derived-midbrain-dopaminergic-neurons
#20
Maroof M Adil, Tandis Vazin, Badriprasad Ananthanarayanan, Gonçalo M C Rodrigues, Antara T Rao, Rishikesh U Kulkarni, Evan W Miller, Sanjay Kumar, David V Schaffer
Cell replacement therapies have broad biomedical potential; however, low cell survival and poor functional integration post-transplantation are major hurdles that hamper clinical benefit. For example, following striatal transplantation of midbrain dopaminergic (mDA) neurons for the treatment of Parkinson's disease (PD), only 1-5% of the neurons typically survive in preclinical models and in clinical trials. In general, resource-intensive generation and implantation of larger numbers of cells are used to compensate for the low post-transplantation cell-survival...
May 5, 2017: Biomaterials
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