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https://www.readbyqxmd.com/read/27914091/toward-clinical-use-of-the-igg-specific-enzymes-ides-and-endos-against-antibody-mediated-diseases
#1
Mattias Collin, Lars Björck
The endoglycosidase EndoS and the protease IdeS from the human pathogen Streptococcus pyogenes are immunomodulating enzymes hydrolyzing human IgG. IdeS cleaves IgG in the lower hinge region, while EndoS hydrolyzes the conserved N-linked glycan in the Fc region. Both enzymes are remarkably specific for human IgG that after hydrolysis loses most of its effector functions, such as binding to leukocytes and complement activation, all contributing to bacterial evasion of adaptive immunity. However, taken out of their infectious context, we and others have shown that IdeS and EndoS can alleviate autoimmune disease in a number of animal models of antibody-mediated disorders...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27913584/nitro-fatty-acid-pharmacokinetics-in-the-adipose-tissue-compartment
#2
Marco Fazzari, Nicholas K H Khoo, Steven R Woodcock, Diane K Jorkasky, Lihua Li, Francisco J Schopfer, Bruce A Freeman
Electrophilic nitro-fatty acids (NO2-FAs) promote adaptive and anti-inflammatory cell signaling responses as a result of an electrophilic character that supports post-translational protein modifications. A unique pharmacokinetic profile is expected for NO2-FAs because of an ability to undergo reversible reactions including Michael additions with biological cysteine-containing proteins and esterification into complex lipids. Herein we report via quantitative whole-body autoradiography analysis of rats gavaged with radiolabeled 10-nitro-[14C]oleic acid, preferential accumulation in adipose tissue over two weeks...
December 2, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27913277/specific-stabilization-of-cftr-by-phosphatidylserine
#3
Ellen Hildebrandt, Netaly Khazanov, John C Kappes, Qun Dai, Hanoch Senderowitz, Ina L Urbatsch
The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR, ABCC7) is a plasma membrane chloride ion channel in the ABC transporter superfamily. CFTR is a key target for cystic fibrosis drug development, and its structural elucidation would advance those efforts. However, the limited in vivo and in vitro stability of the protein, particularly its nucleotide binding domains, has made structural studies challenging. Here we demonstrate that phosphatidylserine uniquely stimulates and thermally stabilizes the ATP hydrolysis function of purified human CFTR...
November 29, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27913224/a-novel-cross-linked-enzyme-aggregates-cleas-of-papain-and-neutrase-production-partial-characterization-and-application
#4
Zhongqin Chen, Yanwei Wang, Wei Liu, Jingya Wang, Haixia Chen
The neutrase (EC 3.4.24.4) and papain (EC 3.4.22.2) were together immobilized ascross-linked enzyme aggregates (N-P-CLEAs) and their properties were characterized. The influence of the precipitant, cross-linking ratio of glutaraldehyde and cross-linking time were investigated. Ethanol was selected as the more efficient precipitant compared with ammonium sulfate. The proper cross-linking ratio of enzyme and glutaraldehyde was 1:5 (v/v) and the optimized cross-linking time was 4h. N-P-CLEAs showed obvious improvement in thermal stability and pH stability than the free enzyme (P<0...
November 29, 2016: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/27913182/virtual-screening-and-biophysical-studies-lead-to-hsp90-inhibitors
#5
Renjie Huang, Daniel M Ayine-Tora, M Nasri Muhammad Rosdi, Yu Li, Jóhannes Reynisson, Ivanhoe K H Leung
Heat shock protein 90 (HSP90) is a molecular chaperone that plays important functional roles in cells. The chaperone activity of HSP90 is regulated by the hydrolysis of ATP at the protein's N-terminal domain. HSP90, in particular the N-terminal domain, is a current inhibition target for therapeutic treatments of cancers. This paper describes an application of virtual screening, thermal shift assaying and protein NMR spectroscopy leading to the discovery of HSP90 inhibitors that contain the resorcinol structure...
November 23, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27913171/effects-of-hydraulic-retention-time-hrt-on-denitrification-using-waste-activated-sludge-thermal-hydrolysis-liquid-and-acidogenic-liquid-as-carbon-sources
#6
Yiding Guo, Liang Guo, Mei Sun, Yangguo Zhao, Mengchun Gao, Zonglian She
Waste activated sludge (WAS) internal carbon source can efficiently and economically enhance denitrification, and hydraulic retention time (HRT) is one of the most important operational parameters for denitrification. The effects of HRT on denitrification were investigated with WAS thermal hydrolysis liquid and acidogenic liquid as carbon sources in this study. The optimal HRT was 12h for thermal hydrolysis liquid and 8h for acidogenic liquid, with NO3(-)-N removal efficiency of 91.0% and 97.6%, respectively...
November 15, 2016: Bioresource Technology
https://www.readbyqxmd.com/read/27913169/liquid-nitrogen-pretreatment-of-eucalyptus-sawdust-and-rice-hull-for-enhanced-enzymatic-saccharification
#7
Rafael Castoldi, Vanesa G Correa, Gutierrez Rodrigues de Morais, Cristina G M de Souza, Adelar Bracht, Rosely A Peralta, Regina F Peralta-Muniz Moreira, Rosane M Peralta
In this work, liquid nitrogen was used for the first time in the pretreatment of plant biomasses for purposes of enzymatic saccharification. After treatment (cryocrushing), the initial rates of the enzymatic hydrolysis of eucalyptus sawdust and rice hull were increased more than ten-fold. Cryocrushing did not modify significantly the contents of cellulose, hemicellulose and lignin in both eucalyptus sawdust and rice hulls. However, substantial disorganization of the lignocellulosic materials in consequence of the pretreatment could be observed by electron microscopy...
November 25, 2016: Bioresource Technology
https://www.readbyqxmd.com/read/27912969/triterpenoid-saponins-with-anti-inflammatory-activities-from-ilex-pubescens-roots
#8
Peng Wu, Hui Gao, Jian-Xin Liu, Liang Liu, Hua Zhou, Zhong-Qiu Liu
Seven triterpenoid saponins, named ilexsaponin I-O, along with twelve known ones, were isolated from the roots of Ilex pubescens. The structures of all compounds were elucidated by use of extensive spectroscopic methods (IR, HR-ESI-MS, and 1D and 2D NMR). Sugar residues obtained after acid hydrolysis were identified by TLC and HPLC. The in vitro anti-inflammatory effects of the triterpenoid saponins were also evaluated in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Among the isolated saponins, seven compounds were shown to inhibit LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production by suppressing the expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), respectively, in LPS-stimulated RAW 264...
November 29, 2016: Phytochemistry
https://www.readbyqxmd.com/read/27912968/validation-of-a-thin-layer-chromatography-densitometry-method-for-the-characterization-of-invertase-activity
#9
Justine Ferey, David Da Silva, Sophie Bravo-Veyrat, Pierre Lafite, Richard Daniellou, Benoît Maunit
This paper presents a kinetic study of invertase, a specific fructofuranosidase cloned from the Leishmania major genome. The kinetic parameters of the β-d-fructofuranosidase from Leishmania major (BfrA) were determined using Thin-Layer Chromatography (TLC) and UV-densitometry (TLC@UV) specifically developed for the separation and detection of three carbohydrates namely sucrose, glucose and fructose. Separation was performed on TLC silica gel 60 F254 plates impregnated with sodium bisulphate and citrate and heated prior to development...
November 25, 2016: Journal of Chromatography. A
https://www.readbyqxmd.com/read/27912125/feooh-graphene-oxide-nanocomposites-for-fluoride-removal-from-water-acetate-mediated-nano-feooh-growth-and-adsorption-mechanism
#10
Liyuan Kuang, Yuyang Liu, Dandan Fu, Yaping Zhao
Fluoride adsorption capacity in water matrices depends highly on the properties of each component of the adsorption system, the most important one of these is the physchemical properties of the adsorbent. Nanoparticle Goethite anchored onto graphene oxide (FeOOH+Ac/GO) and rice spike-like Akaganeite anchored onto graphene oxide (FeOOH/GO) were synthesized via an in-situ hydrolysis procedure and compared their fluoride adsorption performances in order to address the effect of crystalline structure growth induced by acetate sodium (NaAc), one important organic ligand in water and soil...
November 21, 2016: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/27911925/attenuation-of-quorum-sensing-regulated-virulence-of-pectobacterium-carotovorum-subsp-carotovorum-through-an-ahl-lactonase-produced-by-lysinibacillus-sp-gs50
#11
Sneha S Garge, Anuradha S Nerurkar
Quorum sensing (QS) is a mechanism in which Gram negative bacterial pathogens sense their population density through acyl homoserine lactones (AHLs) and regulate the expression of virulence factors. Enzymatic degradation of AHLs by lactonases, known as quorum quenching (QQ), is thus a potential strategy for attenuating QS regulated bacterial infections. We characterised the QQ activity of soil isolate Lysinibacillus sp. Gs50 and explored its potential for controlling bacterial soft rot of crop plants. Lysinibacillus sp...
2016: PloS One
https://www.readbyqxmd.com/read/27911800/an-%C3%AE-%C3%AE-hydrolase-fold-protein-in-the-biosynthesis-of-thiostrepton-exhibits-a-dual-activity-for-endopeptidyl-hydrolysis-and-epoxide-ring-opening-macrocyclization
#12
Qingfei Zheng, Shoufeng Wang, Panpan Duan, Rijing Liao, Dandan Chen, Wen Liu
Thiostrepton (TSR), an archetypal bimacrocyclic thiopeptide antibiotic that arises from complex posttranslational modifications of a genetically encoded precursor peptide, possesses a quinaldic acid (QA) moiety within the side-ring system of a thiopeptide-characteristic framework. Focusing on selective engineering of the QA moiety, i.e., by fluorination or methylation, we have recently designed and biosynthesized biologically more active TSR analogs. Using these analogs as chemical probes, we uncovered an unusual indirect mechanism of TSR-type thiopeptides, which are able to act against intracellular pathogens through host autophagy induction in addition to direct targeting of bacterial ribosome...
November 23, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27911799/mechanism-of-the-intrinsic-arginine-finger-in-heterotrimeric-g-proteins
#13
Daniel Mann, Christian Teuber, Stefan A Tennigkeit, Grit Schröter, Klaus Gerwert, Carsten Kötting
Heterotrimeric G proteins are crucial molecular switches that maintain a large number of physiological processes in cells. The signal is encoded into surface alterations of the Gα subunit that carries GTP in its active state and GDP in its inactive state. The ability of the Gα subunit to hydrolyze GTP is essential for signal termination. Regulator of G protein signaling (RGS) proteins accelerates this process. A key player in this catalyzed reaction is an arginine residue, Arg178 in Gαi1, which is already an intrinsic part of the catalytic center in Gα in contrast to small GTPases, at which the corresponding GTPase-activating protein (GAP) provides the arginine "finger...
November 28, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27911496/gram-scale-chemical-synthesis-of-base-modified-ribonucleoside-5-o-triphosphates
#14
Muthian Shanmugasundaram, Annamalai Senthilvelan, Anilkumar R Kore
This unit delineates a simple, reliable, straight-forward, general, and efficient chemical method for the synthesis of modified nucleoside-5'-O-triphosphates such as 5-methylcytidine-5'-O-triphosphate (5-Me-CTP), pseudouridine-5'-O-triphosphate (pseudo-UTP), and N(1) -methylpseudouridine-5'-O-triphosphate (N(1) -methylpseudo-UTP), starting from the corresponding nucleoside. The reaction utilizes an improved protection-free "one-pot, three-step" Ludwig synthetic strategy that involves the monophosphorylation of the nucleoside with phosphorous oxychloride followed by reaction with tributylammonium pyrophosphate and subsequent hydrolysis of the resulting cyclic intermediate to furnish the corresponding ribonucleoside triphosphate (NTP) in moderate yields...
December 1, 2016: Current Protocols in Nucleic Acid Chemistry
https://www.readbyqxmd.com/read/27911418/synthesis-and-characterization-of-fe-doped-aluminosilicate-nanotubes-with-enhanced-electron-conductive-properties
#15
Ehsan Shafia, Serena Esposito, Elnaz Bahadori, Marco Armandi, Maela Manzoli, Barbara Bonelli
The goal of the protocol is to synthesize Fe-doped aluminosilicate nanotubes of the imogolite type with the formula (OH)3Al2-xFexO3SiOH. Doping with Fe aims at lowering the band gap of imogolite, an insulator with the chemical formula (OH)3Al2O3SiOH, and at modifying its adsorption properties towards azo-dyes, an important class of organic pollutants of both wastewater and groundwater. Fe-doped nanotubes are obtained in two ways: by direct synthesis, where FeCl3 is added to an aqueous mixture of the Si and Al precursors, and by post-synthesis loading, where preformed nanotubes are put in contact with a FeCl3•6H2O aqueous solution...
November 15, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27911408/defining-substrate-specificities-for-lipase-and-phospholipase-candidates
#16
Diana X Sahonero-Canavesi, Maritza Zavaleta-Pastor, Lourdes Martínez-Aguilar, Isabel M López-Lara, Otto Geiger
Microorganisms produce a wide spectrum of (phospho)lipases that are secreted in order to make external substrates available for the organism. Alternatively, other (phospho)lipases may be physically associated with the producing organism causing a turnover of intrinsic lipids and frequently giving rise to a remodeling of the cellular membranes. Although potential (phospho)lipases can be predicted with a number of algorithms when the gene/protein sequence is available, experimental proof of the enzyme activities, substrate specificities, and potential physiological functions has frequently not been obtained...
November 23, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27911046/verticillium-dahliae-lysm-effectors-differentially-contribute-to-virulence-on-plant-hosts
#17
Anja Kombrink, Hanna Rovenich, Xiaoqian Shi-Kunne, Eduardo Rojas-Padilla, Grardy C M van den Berg, Emmanouil Domazakis, Ronnie de Jonge, Dirk-Jan Valkenburg, Andrea Sánchez-Vallet, Michael F Seidl, Bart P H J Thomma
Chitin-binding LysM effectors contribute to virulence of various plant pathogenic fungi that are causal agents of foliar diseases. Here, we report on LysM effectors of the soil-borne fungal vascular wilt pathogen Verticillium dahliae. Comparative genomics revealed three core LysM effectors that are conserved in a collection of V. dahliae strains. Remarkably, and in contrast to the previously studied LysM effectors of other plant pathogens, no expression of core LysM effectors was monitored in planta in a taxonomically diverse panel of host plants...
December 2, 2016: Molecular Plant Pathology
https://www.readbyqxmd.com/read/27910990/a-ph-responsive-sequential-disassembly-nanohybrid-for-mitochondrial-targeting
#18
Lijia Li, Wei Sun, Lian Li, Yuanyuan Liu, Lei Wu, Fengling Wang, Zhou Zhou, Zhirong Zhang, Yuan Huang
Cationic materials have been reported as promising tools for targeting to mitochondria which are the "power houses" and "metabolic garbage keepers" of cells. However, their positive nature also restricts their in vivo application due to the quick clearance. Herein, we fabricated a nanohybrid consisting of the pH-responsive N-(2-hydroxypropyl)methacrylamide (HPMA) co-polymer (R-P) shells and positive mesoporous silica nanoparticle cores via electrostatic interaction. The anticancer drug, docetaxel (DTX), was encapsulated in the positive MSN cores (MSN-DTX)...
December 2, 2016: Nanoscale
https://www.readbyqxmd.com/read/27910937/biohydrogen-production-from-enzymatic-hydrolysis-of-food-waste-in-batch-and-continuous-systems
#19
Wei Han, Yingting Yan, Yiwen Shi, Jingjing Gu, Junhong Tang, Hongting Zhao
In this study, the feasibility of biohydrogen production from enzymatic hydrolysis of food waste was investigated. Food waste (solid-to-liquid ratio of 10%, w/v) was first hydrolyzed by commercial glucoamylase to release glucose (24.35 g/L) in the food waste hydrolysate. Then, the obtained food waste hydrolysate was used as substrate for biohydrogen production in the batch and continuous (continuous stirred tank reactor, CSTR) systems. It was observed that the maximum cumulative hydrogen production of 5850 mL was achieved with a yield of 245...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27910741/topotecan-liposomes-a-visit-from-a-molecular-to-a-therapeutic-platform
#20
Shivani Saraf, Ankit Jain, Pooja Hurkat, Sanjay Kumar Jain
Topotecan (TPT), a potent anticancer camptothecin analog, is well described for the treatment of ovarian cancer, but has also anticancer activity against small-cell and non-small-cell lung cancer, breast cancer, and acute leukemia. Various nanocarriers, including liposomes, have been exploited for targeted delivery of TPT. However, there are a number of challenges with TPT delivery using TPT liposomes (TLs), such as low encapsulation efficiency, physiological pH labile E ring (hydrolysis), accelerated blood clearance, multidrug resistance, and cancer metastases...
2016: Critical Reviews in Therapeutic Drug Carrier Systems
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