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Thomas J Lawton, Amy C Rosenzweig
Nature utilizes two groups of enzymes to catalyze methane conversions, methyl-coenzyme M reductases (MCRs) and methane monooxygenases (MMOs). These enzymes have been difficult to incorporate into industrial processes due to their complexity, poor stability, and lack of recombinant tractability. Despite these issues, new ways of preparing and stabilizing these enzymes have recently been discovered, and new mechanistic insight into how MCRs and MMOs break the C-H bond in nature's most inert hydrocarbon have been obtained...
October 18, 2016: Current Opinion in Chemical Biology
B Li, J Liu, Y Y Zhang, P Q Wang, Y N Yu, R X Kang, H L Wu, X X Zhang, Z Wang, Y Y Wang
Module-based methods have made much progress in deconstructing biological networks. However, it is a great challenge to quantitatively compare the topological structural variations of modules (allosteric modules [AMs]) under different situations. A total of 23, 42, and 15 coexpression modules were identified in baicalin (BA), jasminoidin (JA), and ursodeoxycholic acid (UA) in a global anti-ischemic mice network, respectively. Then, we integrated the methods of module-based consensus ratio (MCR) and modified Zsummary module statistic to validate 12 BA, 22 JA, and 8 UA on-modules based on comparing with vehicle...
October 19, 2016: CPT: Pharmacometrics & Systems Pharmacology
Dennis G Hall, Taras Rybak, Tristan Verdelet
Multicomponent reactions (MCR), transformations employing three or more simple substrates in a single and highly atom-economical operation, are very attractive in both natural product synthesis and diversity-oriented synthesis of druglike molecules. Several popular multicomponent reactions were designed by combining two well-established individual reactions that utilize mutually compatible substrates. In this regard, it is not surprising that the merging of two reactions deemed as workhorses of stereoselective synthesis, the Diels-Alder cycloaddition and carbonyl allylboration, would produce a powerful and highly versatile tandem MCR process...
October 18, 2016: Accounts of Chemical Research
Melanie M Sinanian, Daniel Wesley Cook, Sarah C Rutan, Dayanjan S Wijesinghe
Methods such as liquid chromatography coupled with high resolution mass spectrometry (LC-HRMS) are crucial for differentiating compounds with highly similar masses. This is a necessity when analyzing highly complex samples; however, the size of high resolution LC-HRMS datasets can cause difficulties when applying advanced data analysis techniques. In this work, LC-HRMS analyses of known amphetamine samples and unknown bacterial lipid samples were carried out and multivariate curve resolution-alternating least squares (MCR-ALS) was applied to the data to obtain mathematical separation of overlapped analyte signals...
October 18, 2016: Analytical Chemistry
Rafael Laso-Pérez, Gunter Wegener, Katrin Knittel, Friedrich Widdel, Katie J Harding, Viola Krukenberg, Dimitri V Meier, Michael Richter, Halina E Tegetmeyer, Dietmar Riedel, Hans-Hermann Richnow, Lorenz Adrian, Thorsten Reemtsma, Oliver Lechtenfeld, Florin Musat
The anaerobic formation and oxidation of methane involve unique enzymatic mechanisms and cofactors that are believed to be all specific for C1-compounds. Here we found that an anaerobic thermophilic enrichment culture composed of dense consortia of archaea and bacteria apparently uses partly similar pathways to oxidize the C4-hydrocarbon butane. The archaea, proposed genus Candidatus Syntrophoarchaeum, showed the characteristic autofluorescence of methanogens, and contained highly expressed genes encoding enzymes similar to methyl-coenzyme M reductase (MCR)...
October 17, 2016: Nature
John Osei Sekyere
A review of the literature was undertaken to delineate the current level and mechanisms of resistance to carbapenems, colistin, and tigecycline in South Africa. Thirty-two English publications and 32 National Institute of Communicable Diseases communiqués identified between early January 2000 and 20 May, 2016 showed substantial reports of NDM (n = 860), OXA-48 (n = 584), VIM (n = 131), and IMP (n = 45) carbapenemases within this period, mainly in Klebsiella pneumoniae (n = 1138), Acinetobacter baumannii (n = 332), Enterobacter cloacae (n = 201), and Serratia marcescens (n = 108)...
2016: Frontiers in Public Health
Sarah Tully, Adrian Wells, Melissa Pyle, Jemma Hudson, Andrew Gumley, David Kingdon, Matthias Schwannauer, Douglas Turkington, Anthony P Morrison
Responses to psychotic experiences are central to cognitive models of psychosis. The current study aimed to develop and validate a self-report measure of common responses to the experience of psychosis. This measure is needed as cognitive and behavioural responses are implicated in the maintenance of psychosis, but there is currently no measure that comprehensively assesses these maintaining factors. The Measure of Common Responses to psychosis (MCR) was developed and utilised in a sample of 487 participants who met criteria for treatment-resistant schizophrenia...
October 13, 2016: Schizophrenia Research
Qingjing Wang, Zhencui Li, Jingxia Lin, Xiuna Wang, Xianbo Deng, Youjun Feng
The emergence of the mobilized colistin resistance gene, representing a novel mechanism for bacterial drug resistance, challenges the last resort against the severe infections by Gram-negative bacteria with multi-drug resistances. Very recently, we showed the diversity in the mcr-1-carrying plasmid reservoirs from the gut microbiota. Here, we reported that a similar but more complex scenario is present in the healthy swine populations, Southern China, 2016. Amongst the 1026 pieces of Escherichia coli isolates from 3 different pig farms, 302 E...
October 12, 2016: Oncotarget
Zhijie Liu, Tiangang Liu
Acrylic acid and propionic acid are important chemicals requiring affordable, renewable production solutions. Here, we metabolically engineered Escherichia coli with genes encoding components of the 3-hydroxypropionate/4-hydroxybutyrate cycle from Metallosphaera sedula for conversion of glucose to acrylic and propionic acids. To construct an acrylic acid-producing pathway in E. coli, heterologous expression of malonyl-CoA reductase (MCR), malonate semialdehyde reductase (MSR), 3-hydroxypropionyl-CoA synthetase (3HPCS), and 3-hydroxypropionyl-CoA dehydratase (3HPCD) from M...
October 8, 2016: Journal of Industrial Microbiology & Biotechnology
Pierre Regenass, Stéphanie Riché, Florent Péron, Didier Rognan, Marcel Hibert, Nicolas Girard, Dominique Bonnet
A rapid and atom economical multicomponent synthesis of complex aza-diketopiperazines (aza-DKPs) driven by Rh(i)-catalyzed hydroformylation of alkenylsemicarbazides is described. Combined with catalytic amounts of acid and the presence of nucleophilic species, this unprecedented multicomponent reaction (MCR) enabled the formation of six bonds and a controlled stereocenter from simple substrates. The efficacy of the strategy was demonstrated with a series of various allyl-substituted semicarbazides and nucleophiles leading to the preparation of 3D-shaped bicyclic aza-DKPs...
September 21, 2016: Organic & Biomolecular Chemistry
Milad Khorasani, Magnus Edinger, Dhara Raijada, Johan Bøtker, Johanna Aho, Jukka Rantanen
Hot-melt extrusion and 3D printing are enabling manufacturing approaches for patient-centred medicinal products. Hot-melt extrusion is a flexible and continuously operating technique which is a crucial part of a typical processing cycle of printed medicines. In this work we use hot-melt extrusion for manufacturing of medicinal films containing indomethacin (IND) and polycaprolactone (PCL), extruded strands with nitrofurantoin monohydrate (NFMH) and poly (ethylene oxide) (PEO), and feedstocks for 3D printed dosage forms with nitrofurantoin anhydrate (NFAH), hydroxyapatite (HA) and poly (lactic acid) (PLA)...
October 5, 2016: International Journal of Pharmaceutics
Olga Monago-Maraña, Rocío L Pérez, Graciela Mónica Escandar, Arsenio Muñoz de la Peña, Teresa Galeano-Díaz
This work presents a strategy for quantifying polycyclic aromatic hydrocarbons (PAHs) in smoked paprika samples. For this, a liquid chromatographic method with fluorescence detection (HPLC-FLD) has been optimized. In order to resolve some interferences co-eluting with the target analytes, the second order multivariate curve resolution - alternating least-squares (MCR-ALS) algorithm has been employed combined with this liquid chromatographic method. Among the eight PAHs quantified (fluorene, phenantrene, pyrene, chrysene, benzo(a)anthracene, benzo(b)fluorantene and benzo(a)pyrene) by HPLC-FLD, only in the case of fluorene, pyrene and benzo(b)fluorantene was necessary to apply the second-order algorithm for their resolution...
October 7, 2016: Journal of Agricultural and Food Chemistry
Xiaoxing Huang, Wei Huang, Li Li, Xihuan Sun, Siyang Song, Qingyan Xu, Lianru Zhang, Bang-Guo Wei, Xianming Deng
Marine natural products are served as attractive source of anticancer therapeutics, with the great success of "first-in-class" drugs, such as Yondelis, Halaven, and Brentuximab vendotin. Lagunamides A-C from marine cyanobacterium, Lyngbya majuscula, exhibit exquisite growth inhibitory activities against cancer cells. In this study, we have systematically investigated the structure-activity relationships (SAR) of a concise collection of lagunamide A and its analogs constructed by total chemical synthesis against a broad panel of cancer cells derived from various tissues or organs, including A549, HeLa, U2OS, HepG2, BEL-7404, BGC-823, HCT116, MCR-7, HL-60, and A375...
October 7, 2016: Molecular Pharmaceutics
Shuntaro Arase, Kanta Horie, Takashi Kato, Akira Noda, Yasuhiro Mito, Masatoshi Takahashi, Toshinobu Yanagisawa
Multivariate curve resolution-alternating least squares (MCR-ALS) method was investigated for its potential to accelerate pharmaceutical research and development. The fast and efficient separation of complex mixtures consisting of multiple components, including impurities as well as major drug substances, remains a challenging application for liquid chromatography in the field of pharmaceutical analysis. In this paper we suggest an integrated analysis algorithm functioning on a matrix of data generated from HPLC coupled with photo-diode array detector (HPLC-PDA) and consisting of the mathematical program for the developed multivariate curve resolution method using an expectation maximization (EM) algorithm with a bidirectional exponentially modified Gaussian (BEMG) model function as a constraint for chromatograms and numerous PDA spectra aligned with time axis...
October 21, 2016: Journal of Chromatography. A
I Hamdi, G Buntinx, A Perrier, O Devos, N Jaïdane, S Delbaere, A K Tiwari, J Dubois, M Takeshita, Y Wada, S Aloïse
The photoswitching and competitive processes of the referent photochromic diarylethene derivative 1,2-bis(2,4-dimethyl-5-phenyl-3-thienyl)perfluorocyclopentene (DTE) and a novel bridged analog DTE-m5 have been investigated by state-of-the-art TD-DFT calculations and ultrafast spectroscopy supported by advanced chemometric data treatments. Focusing on DTE, the overall deactivation pathway of both antiparallel (AP) and parallel (P) conformers of the open form (OF) (1 : 1 in solution) has been resolved and rationalized starting from the Franck-Condon (FC) region to the ground state recovery...
October 12, 2016: Physical Chemistry Chemical Physics: PCCP
Chiara Carnevali, Marina Morganti, Erika Scaltriti, Luca Bolzoni, Stefano Pongolini, Gabriele Casadei
The first case of plasmid-mediated resistance to colistin due to the gene mcr-1 was reported in China in late 2015 (1).….
October 3, 2016: Antimicrobial Agents and Chemotherapy
Lívia Viganor, Orla Howe, Pauraic McCarron, Malachy McCann, Michael Devereux
The "antibiotic era", characterized by the overuse and misuse of antibiotics, over the last half-century has culminated in the present critical "era of resistance". The treatment of bacterial infections is challenging because of a decline in the current arsenal of useful antibiotics and the slow rate of new drug development. The discovery of a new gene (mcr-1) in 2015, which enables bacteria to be highly resistant to polymyxins (such as colistin), the last line of antibiotic defence left, heralds a new level of concern as this gene is susceptible to horizontal gene transfer, with alarming potential to be spread between different bacterial populations, suggesting that the progression from "extensive drug resistance" to "pan-drug resistance" may be inevitable...
October 3, 2016: Current Topics in Medicinal Chemistry
Y Poorna Chandra Rao, D Sugasini, B R Lokesh
Ricebran oil (RBO) is promoted as heart friendly oil because of its ability to maintain serum lipids at desirable levels. Inflammation also plays an important role on cardiovascular health. The role of minor constituents present in unsaponifiable fraction (UF) of RBO on inflammatory markers is not well understood. To evaluate this, we have taken RBO with UF (RBO-N), RBO stripped of UF (RBO-MCR) and RBO-MCR supplemented with UF from RBO (UFRBO) or Gamma-Oryzanol (γ-ORY) were added in AIN-93 diets which was then fed to Wistar rats for a period of 60 days...
October 28, 2016: Biochemical and Biophysical Research Communications
Ioannis Christakis, Rebecca Scott, James Minnion, Joyceline Cuenco, Tricia Tan, Fausto Palazzo, Stephen Bloom
PURPOSE/AIM OF THE STUDY: The pharmacokinetic (PK) parameters in animal models can help optimize novel candidate drugs prior to human trials. However, due to the complexity of pharmacokinetic experiments, their use is limited in academia. We present a novel surgical rat model for investigation of pharmacokinetic parameters and its use in an anti-obesity drug development program. MATERIALS AND METHODS: The model uses anesthetized male Wistar rats, a jugular, a femoral catheter, and an insulin pump for peptide infusion...
September 30, 2016: Journal of Investigative Surgery: the Official Journal of the Academy of Surgical Research
(no author information available yet)
In the report, "Investigation of Escherichia coli Harboring the mcr-1 Resistance Gene - Connecticut, 2016," the Acknowledgments should have included the following: Alycia McNutt, David Santoro, Christina Nishimura, Diane Noel, Katherine A. Kelley Public Health Laboratory, Connecticut Department of Public Health.
2016: MMWR. Morbidity and Mortality Weekly Report
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