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https://www.readbyqxmd.com/read/28920929/structural-investigation-of-nucleophosmin-interaction-with-the-tumor-suppressor-fbw7%C3%AE
#1
A Di Matteo, M Franceschini, A Paiardini, A Grottesi, S Chiarella, S Rocchio, C Di Natale, D Marasco, L Vitagliano, C Travaglini-Allocatelli, L Federici
Nucleophosmin (NPM1) is a multifunctional nucleolar protein implicated in ribogenesis, centrosome duplication, cell cycle control, regulation of DNA repair and apoptotic response to stress stimuli. The majority of these functions are played through the interactions with a variety of protein partners. NPM1 is frequently overexpressed in solid tumors of different histological origin. Furthermore NPM1 is the most frequently mutated protein in acute myeloid leukemia (AML) patients. Mutations map to the C-terminal domain and lead to the aberrant and stable localization of the protein in the cytoplasm of leukemic blasts...
September 18, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28918628/breaking-benzene-aromaticity-computational-insights-into-the-mechanism-of-the-tungsten-containing-benzoyl-coa-reductase
#2
Martin Culka, Simona G Huwiler, Matthias Boll, G Matthias Ullmann
Aromatic compounds are environmental pollutants with toxic and carcinogenic properties. Despite the stability of aromatic rings, bacteria are able to degrade the aromatic compounds into simple metabolites and use them as growth substrates under oxic or even under anoxic conditions. In anaerobic microorganisms, most monocyclic aromatic growth substrates are converted to the central intermediate benzoyl-coenzyme A, which is enzymatically reduced to cyclohexa-1,5-dienoyl-CoA. The strcitly anaerobic bacterium \textit{Geobacter metallireducens} uses the class II benzoyl-CoA reductase complex for this reaction...
September 18, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28917047/detection-of-selenoproteins-by-laser-ablation-inductively-coupled-plasma-mass-spectrometry-la-icp-ms-in-immobilized-ph-gradient-ipg-strips
#3
Jordan Sonet, Sandra Mounicou, Laurent Chavatte
In contrast to other trace elements that are cofactors of enzymes and removed from proteins under denaturing conditions, Se is covalently bound to proteins when incorporated into selenoproteins, since it is a component of selenocysteine aminoacid. It implies that selenoproteins can undergo several biochemical separation methods in stringent and chaotropic conditions and still maintain the presence of selenium in the primary sequence. This feature has been used to develop a method for the detection of trace levels of human selenoproteins in cell extracts without the use of radioactive isotopes...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28914466/supramolecular-hydro-and-ionogels-a-study-of-their-properties-and-antibacterial-activity
#4
Carla Rizzo, Rossella Arrigo, Nadka Tz Dintcheva, Giuseppe Gallo, Francesco Giannici, Renato Noto, Alberto Sutera, Paola Vitale, Francesca D'Anna
Diimidazolium-based organic salts, bearing peptides or aminoacids as anions, have been synthesized and tested for their gelling ability in biocompatible solvents. These low molecular weight salts were successfully used as gelators in phosphate saline buffer and ionic liquids. Then, properties of obtained soft materials were analyzed in terms of melting temperature and gel strength as accounted for by rheological investigation. Gel phase formation was studied using UV-vis and resonance light scattering measurements, whereas morphology of soft materials was analysed using polarized optical microscopy and scanning electron microscopy...
September 15, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28898308/-the-treatment-of-cannabis-dependence-clinical-work-psychotherapy-and-evidence
#5
José Capece, Federico Pavlovsky
Identifying compulsive consumption of marijuana in association with another mental disorder (attentional defcit disorder, bipolar disorder, depression or psychosis) presents the challenge of clarifying validated therapeutic strategies, especially within the teen population, in which it shows the highest prevalence. The ever-increasing prevalence and the need for regional treatments, demand that we approach this health matter as a public health issue. The ideological con?icts related to the necessary decriminalization of consumption and the current debate on the medical use of marijuana often confuse the urgent need to establish effective therapeutic strategies for the population affected by this mental disorder...
November 2016: Vertex: Revista Argentina de Psiquiatriá
https://www.readbyqxmd.com/read/28856729/the-protein-restriction-mimetic-resveratrol-is-an-autophagy-inducer-stronger-than-amino-acid-starvation-in-ovarian-cancer-cells
#6
Alessandra Ferraresi, Rossella Titone, Carlo Follo, Andrea Castiglioni, Giovanna Chiorino, Danny N Dhanasekaran, Ciro Isidoro
The potential benefit of nutrient starvation in the prevention and treatment of cancer is presently under consideration. Resveratrol (RV), a dietary polyphenol acting as a protein (caloric) restriction mimetic, could substitute for amino acid starvation. The effects of starvation and of caloric restriction are mediated, among others, by autophagy, a process that contributes to cell homeostasis by promoting the lysosomal degradation of damaged and redundant self-constituents. Up-regulation of autophagy favors cell survival under nutrient shortage situation, and may drive cancer cells into a non-replicative, dormant state...
August 30, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28851936/putrescine-independent-wound-response-phenotype-is-produced-by-odc-like-rnai-in-planarians
#7
Lucia Cassella, Alessandra Salvetti, Paola Iacopetti, Chiara Ippolito, Claudio Ghezzani, Gregory Gimenez, Eric Ghigo, Leonardo Rossi
Despite increasing evidence indicates polyamines as a convergence point for signaling pathways, including cell growth and differentiation, a unifying concept to interpret their role is still missing. The activity of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis, is tightly regulated by a complex molecular machinery, and the demonstration of the existence of multiple ODC paralogs, lacking decarboxylation activity, suggests additional layers of complexity to the intricate ODC regulatory pathway...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28840514/g%C3%AE-q-p63rhogef-interaction-in-rhoa-rho-kinase-signaling-investigation-in-gitelman-s-syndrome-and-implications-with-hypertension
#8
E Pagnin, V Ravarotto, G Maiolino, E Naso, P A Davis, L A Calò
PURPOSE: Gitelman's syndrome (GS) presents normo-hypotension and absence of cardiovascular-renal remodeling despite high angiotensin II (Ang II), activation of renin-angiotensin-aldosterone system and is a human model of endogenous antagonism of Ang II signaling, opposite to hypertension. GS's clinical presentation leads to questions regarding what features might be responsible. One area of investigation involves Ang II signaling. In hypertensive patients, RhoA/Rho kinase (RhoA/ROCK) pathway activation by Ang II is involved in hypertension development/maintenance and induction of long-term consequences (cardiovascular-renal remodeling), while GS has reduced p63RhoGEF gene and protein levels and ROCK activity...
August 24, 2017: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/28839177/simple-md-based-model-for-oxidative-folding-of-peptides-and-proteins
#9
Sergei A Izmailov, Ivan S Podkorytov, Nikolai R Skrynnikov
Significant strides have been recently made to fold peptides and small proteins in silico using MD simulations. However, facilities are currently lacking to include disulfide bonding in the MD models of protein folding. To address this problem, we have developed a simple empirical protocol to model formation of disulfides, which is perturbation-free, retains the same speed as conventional MD simulations and allows one to control the reaction rate. The new protocol has been tested on 15-aminoacid peptide guanylin containing four cysteine residues; the net simulation time using Amber ff14SB force field was 61 μs...
August 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28835346/the-discovery-of-idx21437-design-synthesis-and-antiviral-evaluation-of-2-%C3%AE-chloro-2-%C3%AE-c-methyl-branched-uridine-pronucleotides-as-potent-liver-targeted-hcv-polymerase-inhibitors
#10
François-René Alexandre, Eric Badaroux, John P Bilello, Stéphanie Bot, Tony Bouisset, Guillaume Brandt, Sylvie Cappelle, Christopher Chapron, Dominique Chaves, Thierry Convard, Clément Counor, Daniel Da Costa, David Dukhan, Marion Gay, Gilles Gosselin, Jean-François Griffon, Kusum Gupta, Brenda Hernandez-Santiago, Massimiliano La Colla, Marie-Pierre Lioure, Julien Milhau, Jean-Laurent Paparin, Jérôme Peyronnet, Christophe Parsy, Claire Pierra Rouvière, Houcine Rahali, Rachid Rahali, Aurélien Salanson, Maria Seifer, Ilaria Serra, David Standring, Dominique Surleraux, Cyril B Dousson
Herein we describe the discovery of IDX21437 35b, a novel RPd-aminoacid-based phosphoramidate prodrug of 2'-α-chloro-2'-β-C-methyluridine monophosphate. Its corresponding triphosphate 6 is a potent inhibitor of the HCV NS5B RNA-dependent RNA polymerase (RdRp). Despite showing very weak activity in the in vitro Huh-7 cell based HCV replicon assay, 35b demonstrated high levels of active triphosphate 6 in mouse liver and human hepatocytes. A biochemical study revealed that the metabolism of 35b was mainly attributed to carboxyesterase 1 (CES1), an enzyme which is underexpressed in HCV Huh-7-derived replicon cells...
September 15, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28822219/regulation-of-protein-function-by-s-nitrosation-and-s-glutathionylation-processes-and-targets-in-cardiovascular-pathophysiology
#11
Eugenia Belcastro, Caroline Gaucher, Alessandro Corti, Pierre Leroy, Isabelle Lartaud, Alfonso Pompella
Decades of chemical, biochemical and pathophysiological research have established the relevance of post-translational protein modifications induced by processes related to oxidative stress, with critical reflections on cellular signal transduction pathways. A great deal of the socalled 'redox regulation' of cell function is in fact mediated through reactions promoted by reactive oxygen and nitrogen species on more or less specific aminoacid residues in proteins, at various levels within the cell machinery. Modifications involving cysteine residues have received most attention, due to the critical roles they play in determining the structure/function correlates in proteins...
August 28, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28810191/structure-function-studies-of-bpp-brachynh2-and-synthetic-analogues-thereof-with-angiotensin-i-converting-enzyme
#12
Daniel D R Arcanjo, Andreanne G Vasconcelos, Lucas A Nascimento, Ana Carolina Mafud, Alexandra Plácido, Michel M M Alves, Cristina Delerue-Matos, Marcelo P Bemquerer, Nuno Vale, Paula Gomes, Eduardo B Oliveira, Francisco C A Lima, Yvonne P Mascarenhas, Fernando Aécio A Carvalho, Ulf Simonsen, Ricardo M Ramos, José Roberto S A Leite
The vasoactive proline-rich oligopeptide termed BPP-BrachyNH2 (H-WPPPKVSP-NH2) induces in vitro inhibitory activity of angiotensin I-converting enzyme (ACE) in rat blood serum. In the present study, the removal of N-terminal tryptophan or C-terminal proline from BPP-BrachyNH2 was investigated in order to predict which structural components are important or required for interaction with ACE. Furthermore, the toxicological profile was assessed by in silico prediction and in vitro MTT assay. Two BPP-BrachyNH2 analogues (des-Trp(1)-BPP-BrachyNH2 and des-Pro(8)-BPP-BrachyNH2) were synthesized, and in vitro and in silico ACE inhibitory activity and toxicological profile were assessed...
August 7, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28782624/post-translational-modifications-of-the-mitochondrial-f1fo-atpase
#13
REVIEW
Salvatore Nesci, Fabiana Trombetti, Vittoria Ventrella, Alessandra Pagliarani
BACKGROUND: The mitochondrial F1FO-ATPase has the main role in synthesizing most of ATP, thus providing energy to living cells, but it also works in reverse and hydrolyzes ATP, depending on the transmembrane electrochemical gradient. Within the same complex the vital role of the enzyme of life coexists with that of molecular switch to trigger programmed cell death. The two-faced vital/lethal role makes the enzyme complex an intriguing biochemical target to fight pathogens resistant to traditional therapies and diseases linked to mitochondrial dysfunctions...
August 4, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28764371/toward-reliable-modeling-of-s-nitrosothiol-chemistry-structure-and-properties-of-methyl-thionitrite-ch3sno-an-s-nitrosocysteine-model
#14
Dmitry G Khomyakov, Qadir K Timerghazin
Methyl thionitrite CH3SNO is an important model of S-nitrosated cysteine aminoacid residue (CysNO), a ubiquitous biological S-nitrosothiol (RSNO) involved in numerous physiological processes. As such, CH3SNO can provide insights into the intrinsic properties of the -SNO group in CysNO, in particular, its weak and labile S-N bond. Here, we report an ab initio computational investigation of the structure and properties of CH3SNO using a composite Feller-Peterson-Dixon scheme based on the explicitly correlated coupled cluster with single, double, and perturbative triple excitations calculations extrapolated to the complete basis set limit, CCSD(T)-F12/CBS, with a number of additive corrections for the effects of quadruple excitations, core-valence correlation, scalar-relativistic and spin-orbit effects, as well as harmonic zero-point vibrational energy with an anharmonicity correction...
July 28, 2017: Journal of Chemical Physics
https://www.readbyqxmd.com/read/28761155/spatial-structure-of-tlr4-transmembrane-domain-in-bicelles-provides-the-insight-into-the-receptor-activation-mechanism
#15
Konstantin S Mineev, Sergey A Goncharuk, Marina V Goncharuk, Pavel E Volynsky, Ekaterina V Novikova, Alexander S Aresinev
Toll-like receptors (TLRs) play a key role in the innate and adaptive immune systems. While a lot of structural data is available for the extracellular and cytoplasmic domains of TLRs, and a model of the dimeric full-length TLR3 receptor in the active state was build, the conformation of the transmembrane (TM) domain and juxtamembrane regions in TLR dimers is still unclear. In the present work, we study the transmembrane and juxtamembrane parts of human TLR4 receptor using solution NMR spectroscopy in a variety of membrane mimetics, including phospholipid bicelles...
July 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28753930/pregnancy-proteinuria-plant-based-supplemented-diets-and-focal-segmental-glomerulosclerosis-a-report-on-three-cases-and-critical-appraisal-of-the-literature
#16
Rossella Attini, Filomena Leone, Benedetta Montersino, Federica Fassio, Fosca Minelli, Loredana Colla, Maura Rossetti, Cristiana Rollino, Maria Grazia Alemanno, Antonella Barreca, Tullia Todros, Giorgina Barbara Piccoli
Chronic kidney disease (CKD) is increasingly recognized in pregnant patients. Three characteristics are associated with a risk of preterm delivery or small for gestational age babies; kidney function reduction, hypertension, and proteinuria. In pregnancy, the anti-proteinuric agents (ACE-angiotensin converting enzyme-inhibitors or ARBS -angiotensin receptor blockers) have to be discontinued for their potential teratogenicity, and there is no validated approach to control proteinuria. Furthermore, proteinuria usually increases as an effect of therapeutic changes and pregnancy-induced hyperfiltration...
July 19, 2017: Nutrients
https://www.readbyqxmd.com/read/28739325/d242n-a-kv7-1-lqts-mutation-uncovers-a-key-residue-for-iks-voltage-dependence
#17
Cristina Moreno, Anna Oliveras, Chiara Bartolucci, Carmen Muñoz, Alicia de la Cruz, Diego A Peraza, Juan R Gimeno, Mercedes Martín-Martínez, Stefano Severi, Antonio Felipe, Pier D Lambiase, Teresa Gonzalez, Carmen Valenzuela
KV7.1 and KCNE1 co-assemble to give rise to the IKs current, one of the most important repolarizing currents of the cardiac action potential. Its relevance is underscored by the identification of >500 mutations in KV7.1 and, at least, 36 in KCNE1, that cause Long QT Syndrome (LQTS). The aim of this study was to characterize the biophysical and cellular consequences of the D242N KV7.1 mutation associated with the LQTS. The mutation is located in the S4 transmembrane segment, within the voltage sensor of the KV7...
July 22, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28739271/purification-of-dirucotide-a-synthetic-17-aminoacid-peptide-by-ion-exchange-centrifugal-partition-chromatography
#18
Leslie Boudesocque, Luciano Forni, Agathe Martinez, Jean-Marc Nuzillard, Matthieu Giraud, Jean-Hugues Renault
Dirucotide is a synthetic drug candidate for the treatment of multiple sclerosis. This 17-aminoacid peptide was successfully purified by ion exchange centrifugal partition chromatography. The optimized conditions involved the biphasic methyl tert-butyl ether/acetonitrile/n-butanol/water (2:1:2:5, v/v) solvent system in the descending mode, the di(2-ethylhexyl)phosphoric acid cation-exchanger with an exchanger (di(2-ethylhexyl)phosphoric acid)/dirucotide mole ratio of 100 and Ca(2+) ions in aqueous solution as displacer...
September 1, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28738195/proteomic-and-genetics-insights-on-the-response-of-the-bacteriocinogenic-lactobacillus-sakei-crl1862-during-biofilm-formation-on-stainless-steel-surface-at-10%C3%A2-c
#19
Mariana Pérez-Ibarreche, Lucía M Mendoza, Graciela Vignolo, Silvina Fadda
Some lactic acid bacteria have the ability to form biofilms on food-industry surfaces and this property could be used to control food pathogens colonization. Lactobacillus sakei CR1862 was selected considering its bacteriocinogenic nature and ability to adhere to abiotic surfaces at low temperatures. In this study, the proteome of L. sakei CRL1862 grown either under biofilm on stainless steel surface and planktonic modes of growth at 10°C, was investigated. Using two-dimensional gel electrophoresis, 29 out of 43 statistically significant spots were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry...
July 4, 2017: International Journal of Food Microbiology
https://www.readbyqxmd.com/read/28737896/interfacial-shear-strength-and-adhesive-behavior-of-silk-ionomer-surfaces
#20
Sunghan Kim, Ren D Geryak, Shuaidi Zhang, Ruilong Ma, Rossella Calabrese, David L Kaplan, Vladimir V Tsukruk
The interfacial shear strength between different layers in multilayered structures of layer-by-layer (LbL) microcapsules is a crucial mechanical property to ensure their robustness. In this work, we investigated the interfacial shear strength of modified silk fibroin ionomers utilized in LbL shells, an ionic-cationic pair with complementary ionic pairing, (SF)-poly-l-glutamic acid (Glu) and SF-poly-l-lysine (Lys), and a complementary pair with partially screened Coulombic interactions due to the presence of poly(ethylene glycol) (PEG) segments and SF-Glu/SF-Lys[PEG] pair...
August 4, 2017: Biomacromolecules
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