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https://www.readbyqxmd.com/read/29342418/functional-characterization-of-9-cyp2a13-allelic-variants-by-assessment-of-nicotine-c-oxidation-and-coumarin-7-hydroxylation
#1
Masaki Kumondai, Hiroki Hosono, Masamitsu Maekawa, Hiroaki Yamaguchi, Nariyasu Mano, Akifumi Oda, Noriyasu Hirasawa, Masahiro Hiratsuka
Cytochrome P450 2A13 (CYP2A13) is responsible for the metabolism of chemical compounds such as nicotine, coumarin, and tobacco-specific nitrosamine. Several of these compounds have been recognized as procarcinogens activated by CYP2A13. We recently showed that CYP2A13*2 contributes to inter-individual variations observed in bladder cancer susceptibility because CYP2A13*2 might cause a decrease in enzymatic activity. Other CYP2A13 allelic variants may also affect cancer susceptibility. In this study, we performed an in vitro analysis of the wild-type enzyme (CYP2A13...
November 22, 2017: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29342321/contributions-of-material-properties-and-structure-to-increased-bone-fragility-for-a-given-bone-mass-in-the-ucd-t2dm-rat-model-of-type-2-diabetes
#2
Claire Acevedo, Meghan Sylvia, Eric Schaible, James L Graham, Kimber L Stanhope, Lionel N Metz, Bernd Gludovatz, Ann V Schwartz, Robert O Ritchie, Tamara N Alliston, Peter J Havel, Aaron J Fields
Adults with type 2 diabetes (T2D) have a higher fracture risk for a given bone quantity, but the mechanisms remain unclear. Using a rat model of polygenic obese T2D, we demonstrate that diabetes significantly reduces whole-bone strength for a given bone mass (micro-CT-derived BMC), and we quantify the roles of T2D-induced deficits in material properties versus bone structure, i.e., geometry and microarchitecture. Lumbar vertebrae and ulnae were harvested from 6-month-old lean Sprague-Dawley rats, obese Sprague-Dawley rats, and diabetic obese UCD-T2DM rats (diabetic for 69 ± 7 days; blood glucose >200 mg/dl)...
January 17, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/29342316/solvent-free-enzyme-activity-quick-high-yielding-mechano-enzymatic-hydrolysis-of-cellulose-into-glucose
#3
Fabien Hammerer, Leigh Loots, Jean-Louis Do, J P Daniel Therien, Christopher W Nickels, Tomislav Friscic, Karine Auclair
Mechanochemistry enables enzymatic cleavage of cellulose into glucose without bulk solvents, acids, other aggressive reagents or substrate pre-treatment. This clean mechano-enzymatic process is also directly applicable to biomass, avoids many limitations associated with the use of cellulases, and produces glucose concentrations >3 times the highest obtained by conventional methods.
January 17, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29342141/monitoring-t-cell-dendritic-cell-interactions-in-vivo-by-intercellular-enzymatic-labelling
#4
Giulia Pasqual, Aleksey Chudnovskiy, Jeroen M J Tas, Marianna Agudelo, Lawrence D Schweitzer, Ang Cui, Nir Hacohen, Gabriel D Victora
Interactions between different cell types are essential for multiple biological processes, including immunity, embryonic development and neuronal signalling. Although the dynamics of cell-cell interactions can be monitored in vivo by intravital microscopy, this approach does not provide any information on the receptors and ligands involved or enable the isolation of interacting cells for downstream analysis. Here we describe a complementary approach that uses bacterial sortase A-mediated cell labelling across synapses of immune cells to identify receptor-ligand interactions between cells in living mice, by generating a signal that can subsequently be detected ex vivo by flow cytometry...
January 17, 2018: Nature
https://www.readbyqxmd.com/read/29342140/atomic-structure-of-the-eukaryotic-intramembrane-ras-methyltransferase-icmt
#5
Melinda M Diver, Leanne Pedi, Akiko Koide, Shohei Koide, Stephen B Long
The maturation of RAS GTPases and approximately 200 other cellular CAAX proteins involves three enzymatic steps: addition of a farnesyl or geranylgeranyl prenyl lipid to the cysteine (C) in the C-terminal CAAX motif, proteolytic cleavage of the AAX residues and methylation of the exposed prenylcysteine residue at its terminal carboxylate. This final step is catalysed by isoprenylcysteine carboxyl methyltransferase (ICMT), a eukaryote-specific integral membrane enzyme that resides in the endoplasmic reticulum...
January 17, 2018: Nature
https://www.readbyqxmd.com/read/29342138/%C3%AE-klotho-is-a-non-enzymatic-molecular-scaffold-for-fgf23-hormone-signalling
#6
Gaozhi Chen, Yang Liu, Regina Goetz, Lili Fu, Seetharaman Jayaraman, Ming-Chang Hu, Orson W Moe, Guang Liang, Xiaokun Li, Moosa Mohammadi
The ageing suppressor α-klotho binds to the fibroblast growth factor receptor (FGFR). This commits FGFR to respond to FGF23, a key hormone in the regulation of mineral ion and vitamin D homeostasis. The role and mechanism of this co-receptor are unknown. Here we present the atomic structure of a 1:1:1 ternary complex that consists of the shed extracellular domain of α-klotho, the FGFR1c ligand-binding domain, and FGF23. In this complex, α-klotho simultaneously tethers FGFR1c by its D3 domain and FGF23 by its C-terminal tail, thus implementing FGF23-FGFR1c proximity and conferring stability...
January 17, 2018: Nature
https://www.readbyqxmd.com/read/29342098/mechano-enzymatic-deconstruction-with-a-new-enzymatic-cocktail-to-enhance-enzymatic-hydrolysis-and-bioethanol-fermentation-of-two-macroalgae-species
#7
Sameh Amamou, Cecilia Sambusiti, Florian Monlau, Eric Dubreucq, Abdellatif Barakat
The aim of this study was to explore the efficiency of a mechano-enzymatic deconstruction of two macroalgae species for sugars and bioethanol production, by using a new enzymatic cocktail (Haliatase) and two types of milling modes (vibro-ball: VBM and centrifugal milling: CM). By increasing the enzymatic concentration from 3.4 to 30 g/L, the total sugars released after 72 h of hydrolysis increased (from 6.7 to 13.1 g/100 g TS and from 7.95 to 10.8 g/100 g TS for the green algae U. lactuca and the red algae G...
January 17, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29342092/metabolic-alterations-in-cancer-cells-and-the-emerging-role-of-oncometabolites-as-drivers-of-neoplastic-change
#8
REVIEW
Zhengqiu Zhou, Elochukwu Ibekwe, Yevgen Chornenkyy
The mitochondrion is an important organelle and provides energy for a plethora of intracellular reactions. Metabolic dysregulation has dire consequences for the cell, and alteration in metabolism has been identified in multiple disease states-cancer being one. Otto Warburg demonstrated that cancer cells, in the presence of oxygen, undergo glycolysis by reprogramming their metabolism-termed "aerobic glycolysis". Alterations in metabolism enable cancer cells to gain a growth advantage by obtaining precursors for macromolecule biosynthesis, such as nucleic acids and lipids...
January 17, 2018: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/29341932/synthetic-extracellular-matrix-mimic-hydrogel-improves-efficacy-of-mesenchymal-stromal-cell-therapy-for-ischemic-cardiomyopathy
#9
Maria Chiara Ciuffreda, Giuseppe Malpasso, Cindy Chokoza, Deon Bezuidenhout, Kyle P Goetsch, Manuela Mura, Federica Pisano, Neil H Davies, Massimiliano Gnecchi
BACKGROUND: Mesenchymal stromal cells (MSC) repair infarcted hearts mainly through paracrine mechanisms. Low cell engraftment limits the release of soluble paracrine factors (SF) over time and, consequently, MSC efficacy. We tested whether a synthetic extracellular matrix mimic, a hydrogel containing heparin (H-HG), could ameliorate MSC engraftment and binding/release of SF, thus improving MSC therapy efficacy. METHODS AND RESULTS: In vitro, rat bone-marrow MSC (rBM-MSC) were seeded and grown into H-HG...
January 13, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/29341910/isomalt-and-its-diastereomer-mixtures-as-stabilizing-excipients-with-freeze-dried-lactate-dehydrogenase
#10
Anna-Kaisa Tuderman, Clare J Strachan, Anne M Juppo
The purpose of this research was to study isomalt as a protein-stabilizing excipient with lactate dehydrogenase (LDH) during freeze-drying and subsequent storage and compare it to sucrose, a standard freeze-drying excipient. Four different diastereomer mixtures of isomalt were studied. The stability of the protein was studied with a spectrophotometric enzyme activity test and circular dichroism after freeze-drying and after 21 days of storage at 16% RH. Physical stability was analyzed with differential scanning calorimetry and Karl Fischer titration...
January 13, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29341307/chemical-and-enzymatic-strategies-for-bacterial-and-mammalian-cell-surface-engineering
#11
Xiaobao Bi, Juan Yin, Ashley Chen Guanbang, Chuan-Fa Liu
Cell surface serves important functions such as the regulation of cell-cell and cell-environment interactions. The understanding and manipulation of the cell surface is important for a wide range of fundamental studies of cellular behavior and for biotechnological and medical applications. With the rapid advance of biology, chemistry and materials science, many strategies have been developed for the functionalization of bacterial and mammalian cell surfaces. Here, we review the recent development of chemical and enzymatic approaches to cell surface engineering with particular emphasis on discussing the advantages and limitations of each of these strategies...
January 17, 2018: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29340795/the-sesquiterpene-botrydial-from-botrytis-cinerea-induces-phosphatidic-acid-production-in-tomato-cell-suspensions
#12
Juan Martin D'Ambrosio, Gabriela Gonorazky, Daniela J Sueldo, Javier Moraga, Andrés Arruebarrena Di Palma, Lorenzo Lamattina, Isidro González Collado, Ana Maria Laxalt
The phytotoxin botrydial triggers PA production in tomato cell suspensions via PLD and PLC/DGK activation. PLC/DGK-derived PA is partially required for botrydial-induced ROS generation. Phosphatidic acid (PA) is a phospholipid second messenger involved in the induction of plant defense responses. It is generated via two distinct enzymatic pathways, either via phospholipase D (PLD) or by the sequential action of phospholipase C and diacylglycerol kinase (PLC/DGK). Botrydial is a phytotoxic sesquiterpene generated by the necrotrophic fungus Botrytis cinerea that induces diverse plant defense responses, such as the production of reactive oxygen species (ROS)...
January 16, 2018: Planta
https://www.readbyqxmd.com/read/29339797/a-brave-new-world-of-rna-binding-proteins
#13
REVIEW
Matthias W Hentze, Alfredo Castello, Thomas Schwarzl, Thomas Preiss
RNA-binding proteins (RBPs) are typically thought of as proteins that bind RNA through one or multiple globular RNA-binding domains (RBDs) and change the fate or function of the bound RNAs. Several hundred such RBPs have been discovered and investigated over the years. Recent proteome-wide studies have more than doubled the number of proteins implicated in RNA binding and uncovered hundreds of additional RBPs lacking conventional RBDs. In this Review, we discuss these new RBPs and the emerging understanding of their unexpected modes of RNA binding, which can be mediated by intrinsically disordered regions, protein-protein interaction interfaces and enzymatic cores, among others...
January 17, 2018: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/29339761/new-virulence-factor-csk29544_02616-as-lpxa-binding-partner-in-cronobacter-sakazakii
#14
Seongok Kim, Hyunjin Yoon, Sangryeol Ryu
Cronobacter sakazakii is an opportunistic pathogen that can cause meningitis and necrotizing enterocolitis in premature infants, but its virulence determinants remain largely unknown. In this study, a transposon-mediated random-mutant library of C. sakazakii was used to identify new virulence factors. Compared to wild-type bacteria, a mutant lacking CSK29544_02616 (referred to as labp) was defective in invasion into intestinal epithelial cells (by at least 1000-fold) and showed less phagocytosis by macrophages (by at least 50-fold)...
January 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29339760/biochemical-and-genetic-characterization-of-a-novel-metallo-%C3%AE-lactamase-from-marine-bacterium-erythrobacter-litoralis-htcc-2594
#15
Xia-Wei Jiang, Hong Cheng, Ying-Yi Huo, Lin Xu, Yue-Hong Wu, Wen-Hong Liu, Fang-Fang Tao, Xin-Jie Cui, Bei-Wen Zheng
Metallo-β-lactamases (MBLs) are a group of enzymes that can inactivate most commonly used β-lactam-based antibiotics. Among MBLs, New Delhi metallo-β-lactamase-1 (NDM-1) constitutes an urgent threat to public health as evidenced by its success in rapidly disseminating worldwide since its first discovery. Here we report the biochemical and genetic characteristics of a novel MBL, ElBla2, from the marine bacterium Erythrobacter litoralis HTCC 2594. This enzyme has a higher amino acid sequence similarity to NDM-1 (56%) than any previously reported MBL...
January 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29339739/newborn-screening-of-glucose-6-phosphate-dehydrogenase-deficiency-in-guangxi-china-determination-of-optimal-cutoff-value-to-identify-heterozygous-female-neonates
#16
Chunyun Fu, Shiyu Luo, Qifei Li, Bobo Xie, Qi Yang, Guoxing Geng, Caijuan Lin, Jiasun Su, Yue Zhang, Jin Wang, Zailong Qin, Jingsi Luo, Shaoke Chen, Xin Fan
The aim of this study is to assess the disease incidence and mutation spectrum of glucose-6-phosphate dehydrogenase (G6PD) deficiency in Guangxi, China, and to determine an optimal cutoff value to identify heterozygous female neonates. A total of 130, 635 neonates were screened from the year of 2013 to 2017. Neonates suspected for G6PD deficiency were further analyzed by quantitatively enzymatic assay and G6PD mutation analysis. The overall incidence of G6PD deficiency was 7.28%. A total of 14 G6PD mutations were identified, and different mutations lead to varying levels of G6PD enzymatic activities...
January 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29339505/nonenzymatic-release-of-n7-methylguanine-channels-repair-of-abasic-sites-into-an-ap-endonuclease-independent-pathway-in-arabidopsis
#17
Casimiro Barbado, Dolores Córdoba-Cañero, Rafael R Ariza, Teresa Roldán-Arjona
Abasic (apurinic/apyrimidinic, AP) sites in DNA arise from spontaneous base loss or by enzymatic removal during base excision repair. It is commonly accepted that both classes of AP site have analogous biochemical properties and are equivalent substrates for AP endonucleases and AP lyases, although the relative roles of these two types of enzymes are not well understood. We provide here genetic and biochemical evidence that, in Arabidopsis, AP sites generated by spontaneous loss of N7-methylguanine (N7-meG) are exclusively repaired through an AP endonuclease-independent pathway initiated by FPG, a bifunctional DNA glycosylase with AP lyase activity...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29339495/streamlined-circular-proximity-ligation-assay-provides-high-stringency-and-compatibility-with-low-affinity-antibodies
#18
Roxana Jalili, Joe Horecka, James R Swartz, Ronald W Davis, Henrik H J Persson
Proximity ligation assay (PLA) is a powerful tool for quantitative detection of protein biomarkers in biological fluids and tissues. Here, we present the circular proximity ligation assay (c-PLA), a highly specific protein detection method that outperforms traditional PLA in stringency, ease of use, and compatibility with low-affinity reagents. In c-PLA, two proximity probes bind to an analyte, providing a scaffolding that positions two free oligonucleotides such that they can be ligated into a circular DNA molecule...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29339442/specific-substrate-for-the-assay-of-lysosomal-acid-lipase
#19
Sophia Masi, Naveen Chennamaneni, Frantisek Turecek, C Ronald Scott, Michael H Gelb
BACKGROUND: Deficiency of lysosomal acid lipase (LAL) causes Wolman disease and cholesterol ester storage disease. With the recent introduction of enzyme replacement therapy to manage LAL deficiency comes the need for a reliable assay of LAL enzymatic activity that can be applied to dried blood spots (DBS). METHODS: We prepared and tested a library of analogs of palmitoyl 4-methylumbelifferyl esters to find a highly active and specific substrate for LAL in DBS. The LAL assay was optimized leading to both LC-MS/MS and fluorometric assay of LAL...
January 16, 2018: Clinical Chemistry
https://www.readbyqxmd.com/read/29339289/characterization-of-two-extracellular-%C3%AE-glucosidases-produced-from-the-cellulolytic-fungus-aspergillus-sp-ydj216-and-their-potential-applications-for-the-hydrolysis-of-flavone-glycosides
#20
Jong Min Oh, Jae Pil Lee, Seung Cheol Baek, Seul Gi Kim, Yang Do Jo, Jungho Kim, Hoon Kim
A cellulolytic fungus YDJ216 was isolated from a compost and identified as an Aspergillus sp. strain. Two extracellular β-glucosidases, BGL1 and BGL2, were purified using ultrafiltration, ammonium sulfate fractionation, and High-Q chromatography. Molecular masses of BGL1 and BGL2 were estimated to be 97 and 45 kDa, respectively, by SDS-PAGE. The two enzymes eluted as one peak at 87 kDa by Sephacryl S-200 chromatography, and located at similar positions in a zymogram after intact gel electrophoresis, suggesting BGL1 and BGL2 might be monomeric and dimeric, respectively...
January 12, 2018: International Journal of Biological Macromolecules
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