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https://www.readbyqxmd.com/read/29333671/selective-enrichment-of-n-linked-glycopeptides-and-glycans-by-using-a-dextran-modified-hydrophilic-material
#1
Linlin Chen, Di Ding, Qianying Sheng, Long Yu, Xiuping Liu, Xinmiao Liang
Glycosylation analysis of proteins from biological sources utilizing mass-spectrometry-based approaches is challenging due to the relatively low abundance of glycopeptides, the structural diversity of glycans as well as the co-existing matrices. In this study, a customized dextran-bonded silica-based stationary phase was introduced for selective enrichment of glycopeptides and glycans from complex biological samples. This material has exhibited superior selectivity and broader glycosylation site coverage over commercial Sepharose in glycoproteomic evaluation...
January 15, 2018: Journal of Separation Science
https://www.readbyqxmd.com/read/29332642/current-affairs-future-perspectives-of-tuberculosis-and-antitubercular-agents
#2
REVIEW
Jineetkumar Gawad, Chandrakant Bonde
Tuberculosis (TB) is the major threat for humans from past several decades. Even after advent of several antitubercular drugs, researchers are still struggling for the mycobacterial infections in humans are TB and leprosy. Chronic infections caused by Mycobacterium tuberculosis and Mycobacterium leprae. A particular problem with both of these organisms is that they can survive inside macrophages after phagocytosis, unless these cells are activated by cytokines produced by T-lymphocytes, because of this researchers are not yet succeeded in finding effective treatment on TB...
January 2018: Indian Journal of Tuberculosis
https://www.readbyqxmd.com/read/29332299/similarity-search-combined-with-docking-and-molecular-dynamics-for-novel-hache-inhibitor-scaffolds
#3
Nadia Melo Borges, Geraldo Rodrigues Sartori, Jean F R Ribeiro, Josmar R Rocha, João B L Martins, Carlos A Montanari, Ricardo Gargano
The main purpose of this study was to address the performance of virtual screening methods based on ligands and the protein structure of acetylcholinesterase (AChE) in order to retrieve novel human AChE (hAChE) inhibitors. In addition, a protocol was developed to identify novel hit compounds and propose new promising AChE inhibitors from the ZINC database with 10 million commercially available compounds. In this sense, 3D similarity searches using rapid overlay of chemical structures and similarity analysis through comparison of electrostatic overlay of docked hits were used to retrieve AChE inhibitors from collected databases...
January 13, 2018: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/29330521/rgs7-is-recurrently-mutated-in-melanoma-and-promotes-migration-and-invasion-of-human-cancer-cells
#4
Nouar Qutob, Ikuo Masuho, Michal Alon, Rafi Emmanuel, Isadora Cohen, Antonella Di Pizio, Jason Madore, Abdel Elkahloun, Tamar Ziv, Ronen Levy, Jared J Gartner, Victoria K Hill, Jimmy C Lin, Yael Hevroni, Polina Greenberg, Alexandra Brodezki, Steven A Rosenberg, Mickey Kosloff, Nicholas K Hayward, Arie Admon, Masha Y Niv, Richard A Scolyer, Kirill A Martemyanov, Yardena Samuels
Analysis of 501 melanoma exomes revealed RGS7, which encodes a GTPase-accelerating protein (GAP), to be a tumor-suppressor gene. RGS7 was mutated in 11% of melanomas and was found to harbor three recurrent mutations (p.R44C, p.E383K and p.R416Q). Structural modeling of the most common recurrent mutation of the three (p.R44C) predicted that it destabilizes the protein due to the loss of an H-bond and salt bridge network between the mutated position and the serine and aspartic acid residues at positions 58 as 61, respectively...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330284/novel-intergenically-spliced-chimera-nfatc3-pla2g15-is-associated-with-aggressive-t-all-biology-and-outcome
#5
Jonathan Bond, Christine Tran Quang, Guillaume Hypolite, Mohamed Belhocine, Aurélie Bergon, Gaëlle Cordonnier, Jacques Ghysdael, Elizabeth Macintyre, Nicolas Boissel, Salvatore Spicuglia, Vahid Asnafi
Leukemias are frequently characterized by the expression of oncogenic fusion chimeras that normally arise due to chromosomal rearrangements. Intergenically-spliced chimeric RNAs (ISCs) are transcribed in the absence of structural genomic changes, and aberrant ISC expression is now recognized as a potential driver of cancer. To better understand these potential oncogenic drivers, high-throughput RNA-sequencing (RNA-seq) was performed on T-acute lymphoblastic leukemia (T-ALL) patient specimens (n=24) and candidate T-ALL-related ISCs were identified (n=55; a median of 4 per patient)...
January 12, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29330007/lost-connections-oxytocin-and-the-neural-physiological-and-behavioral-consequences-of-disrupted-relationships
#6
REVIEW
Tobias T Pohl, Larry J Young, Oliver J Bosch
In humans and rodent animal models, the brain oxytocin system is paramount for facilitating social bonds, from the formation and consequences of early-life parent-infant bonds to adult pair bond relationships. In social species, oxytocin also mediates the positive effects of healthy social bonds on the partners' well-being. However, new evidence suggests that the negative consequences of early neglect or partner loss may be mediated by disruptions in the oxytocin system as well. With a focus on oxytocin and its receptor, we review studies from humans and animal models, i...
January 9, 2018: International Journal of Psychophysiology
https://www.readbyqxmd.com/read/29328989/inhibition-of-udp-glucuronosyltransferases-ugts-by-phthalate-monoesters
#7
Zuo Du, Yun-Feng Cao, Sai-Nan Li, Cui-Min Hu, Zhi-Wei Fu, Chun-Ting Huang, Xiao-Yu Sun, Yong-Zhe Liu, Kun Yang, Zhong-Ze Fang
Phthalate monoesters are important metabolites of phthalate esters (PAEs) which have been extensively utilized in industry. This study aims to investigate the inhibition of phthalate monoesters on the activity of various isoforms of UDP-glucuronosyltransferases (UGTs), trying to elucidate the toxicity mechanism of environmental endocrine disruptors from the new perspectives. In vitro recombinant UGTs-catalyzed glucuronidation of 4-methylumbelliferone (4-MU) was employed to evaluate 8 kinds of phthalate monoesters on 11 sorts of main human UGT isoforms...
January 5, 2018: Chemosphere
https://www.readbyqxmd.com/read/29327756/isomeric-and-hybrid-ferrocenyl-cyrhetrenyl-aldimines-a-new-family-of-multifunctional-compounds
#8
Juan Oyarzo, Alejandra Acuña, Hugo Klahn, Rodrigo Arancibia, Carlos P Silva, Ramón Bosque, Concepción López, Mercè Font-Bardía, Carme Calvis, Ramón Messeguer
The synthesis and characterization of two novel and isomeric hybrid ferrocenyl/cyrhetrenyl aldimines [(η5-C5H5)Fe{(η5-C5H4)-CH[double bond, length as m-dash]N-(η5-C5H4)}Re(CO)3] (1) and [(η5-C5H5)Fe{(η5-C5H4)-N[double bond, length as m-dash]CH-(η5-C5H4)}Re(CO)3] (2) are reported. Their X-ray crystal structures reveal that both adopt the E form. However, molecules of 1 and 2 differ in the relative arrangement of the "Fe(η5-C5H5)" and "Re(CO)3" units (anti in 1 and syn in 2). This affects the type of intermolecular interactions, the assembly of the molecules and therefore their crystal architecture...
January 12, 2018: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/29327016/isoenergic-modification-of-whey-protein-structure-by-denaturation-and-crosslinking-using-transglutaminase
#9
Emil G P Stender, Glykeria Koutina, Kristoffer Almdal, Tue Hassenkam, Alan Mackie, Richard Ipsen, Birte Svensson
Transglutaminase (TG) catalyzes formation of covalent bonds between lysine and glutamine side chains and has applications in manipulation of food structure. Physical properties of a whey protein mixture (SPC) denatured either at elevated pH or by heat-treatment and followed by TG catalyzed crosslinking, have been characterised using dynamic light scattering, size exclusion chromatography, flourescence spectroscopy and atomic force microscopy. The degree of enzymatic crosslinking appeared higher for pH- than for heat-denatured SPC...
January 12, 2018: Food & Function
https://www.readbyqxmd.com/read/29326512/evaluating-the-effect-of-different-conditioning-agents-on-the-shear-bond-strength-of-resin-modified-glass-ionomers
#10
Namith Rai, Rajaram Naik, Ravi Gupta, Shobana Shetty, Amith Singh
Aim of the Study: This study aims to evaluate the effects three different conditioning agents on the shear bond strength of resin-modified glass ionomers to human dentin. Materials and Methods: One hundred and twenty recently extracted, caries-free premolars and molars will be cleaned of debris and disinfected in a 0.5% solution of sodium hypochlorite and sterile water for 30 min. The occlusal surface of each tooth will be reduced using conventional model trimmer with water to produce the dentin surface...
October 2017: Contemporary Clinical Dentistry
https://www.readbyqxmd.com/read/29325755/amphotericin-b-albumin-conjugates-synthesis-toxicity-and-anti-fungal-activity
#11
Sneha Gurudevan, Arul Prakash Francis, A Jayakrishnan
Amphotericin B (AmB), a hydrophobic drug with negligible aqueous solubility was conjugated to bovine serum albumin (BSA) via amide bond coupling to give 6 to 8 wt% drug payload. The resulting conjugate was characterized using SDS-PAGE and UV-visible, FTIR and CD spectroscopy. The conjugate was water-soluble to the extent of 150 mg/ml, was non-toxic to HEK 293 T cells at a concentration of 500 μg/ml (equivalent to ~30 μg AmB) and showed hemolysis of <5% at 200 μg/ml (equivalent to ~12 μg AmB) against human erythrocytes in vitro...
January 8, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29322868/in-silico-approaches-to-evaluate-the-molecular-properties-of-organophosphate-compounds-to-inhibit-acetylcholinesterase-activity-in-housefly
#12
Parthiban Marimuthu, Yong-Jin Lee, Byung-Hoon Kim, Seong S Seo
Organophosphate compounds (OPC) have become the primary choice as insecticides and is widely used across the world. Additionally, OPCs were also commonly used as a chemical warfare agent that triggers a great challenge to public safety. Exposure of OPCs to human causes immediate excitation of cholinergic neurotransmission through transient elevation of synaptic acetylcholine (ACh) levels and accumulations. Likewise, prolonged exposure of OPCs can affect the processes in immune response, carbohydrate metabolism, cardiovascular toxicity and several others...
January 11, 2018: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29322360/highly-conserved-arg-residue-of-erfnin-motif-of-pro-domain-is-important-for-ph-induced-zymogen-activation-process-in-cysteine-cathepsins-k-and-l
#13
Pulakesh Aich, Sampa Biswas
Pro-domain of a cysteine cathepsin contains a highly conserved Ex2Rx2Fx2Nx3Ix3N (ERFNIN) motif. The zymogen structure of cathepsins revealed that the Arg(R) residue of the motif is a central residue of a salt-bridge/H-bond network, stabilizing the scaffold of the pro-domain. Importance of the arginine is also demonstrated in studies where a single mutation (Arg → Trp) in human lysosomal cathepsin K (hCTSK) is linked to a bone-related genetic disorder "Pycnodysostosis". In the present study, we have characterized in vitro Arg → Trp mutant of hCTSK and the same mutant of hCTSL...
January 10, 2018: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29321956/an-amebic-protein-disulfide-isomerase-pdi-complements-the-yeast-pdi1-mutation-but-is-unable-to-support-cell-viability-under-er-or-thermal-stress
#14
Rosa E Mares, Marco A Ramos
In eukaryotic cells, protein disulfide isomerases (PDI) are oxidoreductases that catalyze the proper disulfide bond formation during protein folding. The pathobiology of the protozoan parasite Entamoeba histolytica, the causative agent of human amebiasis, depends on secretion of several virulence factors, such as pore-forming peptides and cysteine proteinases. Although the native conformation of these factors is stabilized by disulfide bonds, there is little information regarding the molecular machinery involved in the oxidative folding of amebic proteins...
January 2018: FEBS Open Bio
https://www.readbyqxmd.com/read/29320678/effect-of-ceramide-tail-length-on-the-structure-of-model-stratum-corneum-lipid-bilayers
#15
Timothy C Moore, Remco Hartkamp, Christopher R Iacovella, Annette L Bunge, Clare McCabe
Lipid bilayers composed of non-hydroxy sphingosine ceramide (CER NS), cholesterol (CHOL), and free fatty acids (FFAs), which are components of the human skin barrier, are studied via molecular dynamics simulations. Since mixtures of these lipids exist in dense gel phases with little molecular mobility at physiological conditions, care must be taken to ensure that the simulations become decorrelated from the initial conditions. Thus, we propose and validate an equilibration protocol based on simulated tempering, in which the simulation takes a random walk through temperature space, allowing the system to break out of metastable configurations and hence become decorrelated from its initial configuration...
January 9, 2018: Biophysical Journal
https://www.readbyqxmd.com/read/29317221/extended-impact-of-pin1-catalytic-loop-phosphorylation-revealed-by-s71e-phosphomimetic
#16
Brendan J Mahoney, Meiling Zhang, John S Zintsmaster, Jeffrey W Peng
Pin1 is a two-domain human protein that catalyzes the cis-trans isomerization of pSer/pThr-Pro (pS/T-P) motifs in numerous cell cycle regulatory proteins. These pS/T-P motifs bind to Pin1's peptidyl-prolyl isomerase (PPIase) domain in a catalytic pocket, between an extended catalytic loop and the PPIase domain core. Previous studies showed that post-translational phosphorylation of S71 in the catalytic loop decreases substrate binding affinity and isomerase activity. To define the origins for these effects, we investigated a phosphomimetic Pin1 mutant, S71E-Pin1, using solution nuclear magnetic resonance (NMR)...
January 6, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29317059/pathophysiological-significance-of-protein-hydrophobic-interactions-an-emerging-hypothesis
#17
Marek Kieliszek, Boguslaw Lipinski
Fibrinogen is a unique protein that is converted into an insoluble fibrin in a single enzymatic event, which is a characteristic feature of fibrinogen due to its susceptibility to fibrinolytic degradation and dissolution. Although thrombosis is a result of activated blood coagulation, no explanation is being offered for the persistent presence of fibrin deposits in the affected organs. A classic example is stroke, in which the thrombolytic therapy is effective only during the first 3-4 h after the onset of thrombosis...
January 2018: Medical Hypotheses
https://www.readbyqxmd.com/read/29316361/effects-of-serum-enzyme-thiol-and-forced-degradation-on-the-stabilities-of-%C3%AE-o-conotoxin-gexiva-1-2-and-gexiva-1-4
#18
Shurun Yu, Yong Wu, Pan Xu, Shuai Wang, Dongting Zhangsun, Sulan Luo
αO-conotoxin GeXIVA, which is a potent antagonist of α9α10 nicotinic acetylcholine receptor (nAChR), is of great interest as a potential analgesic for chronic neuropathic pain. It has three isomers, of which both GeXIVA[1,2] and GeXIVA[1,4] showed similar low nanomolar IC50 s in potent blocking rat α9α10 nAChRs. Here, we first reported stabilities of GeXIVA[1,2] and GeXIVA[1,4] in various biochemical circumstances, including human serum, enzymatic degradation and thiol, which would be the key factors to affect stabilities of the two isomers in vivo...
January 9, 2018: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29315804/white-matter-tauopathy-transient-functional-loss-and-novel-myelin-remodeling
#19
Joshua Jackson, Gabby Bianco, Angelo O Rosa, Katrina Cowan, Peter Bond, Oleg Anichtchik, Robert Fern
Early white matter (WM) changes are common in dementia and may contribute to functional decline. We here examine this phenomenon in an induced dementia model for the first time. We report a novel and selective form of myelin injury as the first manifestation of tauopathy in the adult central nervous system. Myelin pathology rapidly followed the induction of a P301 tau mutation associated with fronto-temporal dementia in humans (rTG4510 line). Damage involved focal disruption of the ad-axonal myelin lamella and internal oligodendrocyte tongue process, followed by myelin remodeling with features of re-myelination that included myelin thinning and internodal shortening...
January 8, 2018: Glia
https://www.readbyqxmd.com/read/29314858/panitumumab-modified-with-metal-chelating-polymers-mcp-complexed-to-111in-and-177lu-an-egfr-targeted-theranostic-for-pancreatic-cancer
#20
Sadaf Aghevlian, Yijie Lu, Mitchell A Winnik, David W Hedley, Raymond M Reilly
A metal-chelating polymer (MCP) with a polyglutamide (PGlu) backbone presenting on average 13 DOTA (tetraazacyclododecane-1,4,7,10-tetraacetic acid) chelators for complexing 111In or 177Lu and 10 polyethylene glycol (PEG) chains to minimize liver and spleen uptake was conjugated to anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb), panitumumab. Since panitumumab-MCP may be dual-labeled with 111In and 177Lu for SPECT, or radioimmunotherapy (RIT) exploiting the Auger electrons or β-particle emissions, respectively, we propose that panitumumab-MCP could be a useful theranostic agent EGFR-positive PnCa...
January 9, 2018: Molecular Pharmaceutics
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