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https://www.readbyqxmd.com/read/29602830/3%C3%AE-methyl-neurosteroid-analogs-are-preferential-positive-allosteric-modulators-and-direct-activators-of-extrasynaptic-%C3%AE-gaba-a-receptors-in-the-hippocampus-dentate-gyrus-subfield
#1
Shu-Hui Chuang, Doodipala Samba Reddy
Neurosteroids are powerful modulators of GABA-A receptors. Ganaxolone (3α-hydroxy-3β-methyl-5α-pregnan-20-one, GX) and synthetic analogs of the neurosteroid allopregnanolone (AP) are designed to treat epilepsy and related conditions. However, their precise mechanism of action in native neurons remains unclear. Here, we sought to determine the mode of action of GX and its analogs at GABA-A receptors in native hippocampal neurons by analyzing extrasynaptic receptor-mediated tonic currents and synaptic receptor-mediated phasic currents...
March 30, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29588659/a-novel-acetyl-xylan-esterase-enabling-complete-deacetylation-of-substituted-xylans
#2
Fakhria M Razeq, Edita Jurak, Peter J Stogios, Ruoyu Yan, Maija Tenkanen, Mirjam A Kabel, Weijun Wang, Emma R Master
Background: Acetylated 4- O -(methyl)glucuronoxylan (GX) is the main hemicellulose in deciduous hardwood, and comprises a β-(1→4)-linked xylopyranosyl (Xyl p ) backbone substituted by both acetyl groups and α-(1→2)-linked 4- O -methylglucopyranosyluronic acid (MeGlc p A). Whereas enzymes that target singly acetylated Xyl p or doubly 2,3- O -acetyl-Xyl p have been well characterized, those targeting (2- O -MeGlc p A)3- O -acetyl-Xyl p structures in glucuronoxylan have remained elusive...
2018: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/29572777/synthesis-and-evaluation-of-a-paclitaxel-binding-polymeric-micelle-for-efficient-breast-cancer-therapy
#3
Jiajia Xiang, Bihan Wu, Zhuxian Zhou, Shiqi Hu, Ying Piao, Quan Zhou, Guowei Wang, Jianbin Tang, Xiangrui Liu, Youqing Shen
Paclitaxel (PTX) is one of the most effective anticancer drugs for the treatment of various solid tumors, but its clinical use is limited by its poor solubility, low bioavailability, and severe systemic toxicity. Encapsulation of PTX in polymeric nanoparticles is used to overcome these problems but these micelles still need improvements in stability, pharmacokinetics, therapeutic efficacy, and safety profiles. In this study, we demonstrate a facile fabrication of a stable PTX-binding micelle made from poly (ethylene glycol)-block-dendritic polylysine, whose primary amines were reacted with phenethyl isothiocyanate (PEITC), a hydrophobic anticancer agent under clinical study...
March 19, 2018: Science China. Life Sciences
https://www.readbyqxmd.com/read/29493331/characterization-of-hb-bart-s-hydrops-fetalis-caused-by-sea-and-a-large-novel-%C3%AE-0-thalassemia-deletion
#4
Sheng He, Jihui Li, Peng Huang, Shujie Zhang, Li Lin, Yangjin Zuo, Xiaoxian Tian, Chenguang Zheng, Xiaoxia Qiu, Biyan Chen
Hb Bart's hydrops fetalis is the most severe and generally fatal clinical phenotype of α-thalassemia (α-thal), which is due to the deletion of all four functional α-globin genes of hemoglobin (Hb), resulting in no α-globin chain production (- -/- -). Homozygosity for the - -SEA (Southeast Asian) α-globin gene deletion is the main cause of the Hb Bart's hydrops fetalis in Asia, especially South China. Occasionally, other α0 -thal deletions can also be found. In this study, we report a case with an atypical form of Hb Bart's hydrops fetalis that was caused by - -SEA and a large novel α0 -thal deletion (- -GX ) (Guangxi)...
March 1, 2018: Hemoglobin
https://www.readbyqxmd.com/read/29477770/glucuronoxylan-recognition-by-gh-30-xylanases-a-study-with-enzyme-and-substrate-variants
#5
Katarína Šuchová, Stanislav Kozmon, Vladimír Puchart, Anna Malovíková, Tine Hoff, Kristian B R Mørkeberg Krogh, Peter Biely
XynA from Erwinia chrysanthemi (EcXyn30A), belonging to glycoside hydrolase family 30 subfamily 8, is specialized for hydrolysis of 4-O-methylglucuronoxylan (GX). Carboxyl group of 4-O-methylglucuronic acid serves as a substrate recognition element interacting ionically with positively charged Arg293 of the enzyme. We determined kinetic parameters of EcXyn30A on GX, its methyl ester (GXE) and 4-O-methylglucoxylan (GXR) and compared them with behavior of the enzyme variant in which Arg293 was replaced by Ala...
February 22, 2018: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29439656/genetic-diversity-and-ex-situ-conservation-of-loropetalum-subcordatum-an-endangered-species-endemic-to-china
#6
Bai-Jun Li, Jie-Yu Wang, Zhong-Jian Liu, Xue-Ying Zhuang, Jiu-Xiang Huang
BACKGROUND: Loropetalum subcordatum is an endangered species endemic to China that is characterized by narrow distribution, small population size, and delayed fertilization. However, the genetic diversity of the entire extant natural and ex situ populations has not been assessed to date. In this study, we evaluated the genetic diversity and structure of six natural populations and a single ex situ population (the only known ex situ population of L. subcordatum) using sequence-related amplified polymorphism data...
February 13, 2018: BMC Genetics
https://www.readbyqxmd.com/read/29408208/effect-of-glucocorticoids-on-mirna-expression-spectrum-of-rat-femoral-head-microcirculation-endothelial-cells
#7
Ju'an Yue, Fuyin Wan, Qidong Zhang, Pengfei Wen, Liming Cheng, Ping Li, Wanshou Guo
The study profiled the differential miRNA expression from femoral head bone microvascular endothelial cells (BMECs) between model group and control group to explore the pathogenesis of steroid-induced osteonecrosis of femoral head (ONFH). Twenty 8-week-old Female Sprague-Dawley (SD) rats were randomly divided into control and model groups. Rats in model group received an intraperitoneal injection of 20-μg/kg lipopolysaccharide (LPS) at an interval of 24 h. Then, 24 h later, rats received three doses of 40-mg/kg methylprednisolone by intramuscular injection at intervals of 24 h...
February 2, 2018: Gene
https://www.readbyqxmd.com/read/29389126/quasi-2d-heisenberg-antiferromagnets-cux-pyz-2-bf4-with-x-cl-and-br
#8
Mariusz Kubus, Arianna Lanza, Rebecca Scatena, Leonardo H R Dos Santos, Björn Wehinger, Nicola Casati, Christoph Fiolka, Lukas Keller, Piero Macchi, Christian Rüegg, Karl W Krämer
Two Cu2+ coordination polymers [CuCl(pyz)2](BF4) 1 and [CuBr(pyz)2](BF4) 2 (pyz = pyrazine) were synthesized in the family of quasi two-dimensional (2D) [Cu(pyz)2]2+ magnetic networks. The layer connectivity by monatomic halide ligands results in significantly shorter interlayer distances. Structures were determined by single-crystal X-ray diffraction. Temperature-dependent X-ray diffraction of 1 revealed rigid [Cu(pyz)2]2+ layers that do not expand between 5 K and room temperature, whereas the expansion along the c-axis amounts to 2%...
February 1, 2018: Inorganic Chemistry
https://www.readbyqxmd.com/read/29374817/differential-effects-of-spla2-gv-and-gx-on-cellular-proliferation-and-lipid-accumulation-in-ht29-colon-cancer-cells
#9
Wei Hsum Yap, Su Wen Phang, Nafees Ahmed, Yang Mooi Lim
Secretory phospholipase A2 (sPLA2) group of enzymes have been shown to hydrolyze phospholipids, among which sPLA2 Group V (GV) and Group X (GX) exhibit high selectivity towards phosphatidylcholine-rich cellular plasma membranes. The enzymes have recently emerged as key regulators in lipid droplets formation and it is hypothesized that sPLA2-GV and GX enhanced cell proliferation and lipid droplet accumulation in colon cancer cells (HT29). In this study, cell viability and lipid droplet accumulation were assessed by Resazurin assay and Oil-Red-O staining...
January 27, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29355814/development-of-a-high-efficient-biocatalyst-by-oriented-covalent-immobilization-of-a-novel-recombinant-2-n-deoxyribosyltransferase-from-lactobacillus-animalis
#10
Mariana B Méndez, Cintia W Rivero, Fernando López-Gallego, José M Guisán, Jorge A Trelles
The 2'-N-deoxyribosyltransferases [NDT; EC 2.4.2.6] are a group of enzymes widely used as biocatalysts for nucleoside biosynthesis. In this work, the molecular cloning, expression and purification of a novel NDT from Lactobacillus animalis (LaNDT) have been reported. On the other hand, biocatalyst stability has been significantly enhanced by multipoint covalent immobilization using a hetero-functional support activated with nickel-chelates and glyoxyl groups. The immobilized enzyme could be reused for more than 300 h and stored during almost 3 months without activity loss...
March 20, 2018: Journal of Biotechnology
https://www.readbyqxmd.com/read/29348673/quantification-of-massively-parallel-sequencing-libraries-a-comparative-study-of-eight-methods
#11
Christian Hussing, Marie-Louise Kampmann, Helle Smidt Mogensen, Claus Børsting, Niels Morling
Quantification of massively parallel sequencing libraries is important for acquisition of monoclonal beads or clusters prior to clonal amplification and to avoid large variations in library coverage when multiple samples are included in one sequencing analysis. No gold standard for quantification of libraries exists. We assessed eight methods of quantification of libraries by quantifying 54 amplicon, six capture, and six shotgun fragment libraries. Chemically synthesized double-stranded DNA was also quantified...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29311306/mechanism-specific-assay-design-facilitates-the-discovery-of-nav1-7-selective-inhibitors
#12
Tania Chernov-Rogan, Tianbo Li, Gang Lu, Henry Verschoof, Kuldip Khakh, Steven W Jones, Maureen H Beresini, Chang Liu, Daniel F Ortwine, Steven J McKerrall, David H Hackos, Daniel Sutherlin, Charles J Cohen, Jun Chen
Many ion channels, including Nav1.7, Cav1.3, and Kv1.3, are linked to human pathologies and are important therapeutic targets. To develop efficacious and safe drugs, subtype-selective modulation is essential, but has been extremely difficult to achieve. We postulate that this challenge is caused by the poor assay design, and investigate the Nav1.7 membrane potential assay, one of the most extensively employed screening assays in modern drug discovery. The assay uses veratridine to activate channels, and compounds are identified based on the inhibition of veratridine-evoked activities...
January 23, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29226074/characterization-of-auxiliary-iron-sulfur-clusters-in-a-radical-s-adenosylmethionine-enzyme-pqqe-from-methylobacterium-extorquens-am1
#13
Natsaran Saichana, Katsuyuki Tanizawa, Hiroshi Ueno, Jiří Pechoušek, Petr Novák, Jitka Frébortová
PqqE is a radical S -adenosyl-l-methionine (SAM) enzyme that catalyzes the initial reaction of pyrroloquinoline quinone (PQQ) biosynthesis. PqqE belongs to the SPASM (subtilosin/PQQ/anaerobic sulfatase/mycofactocin maturating enzymes) subfamily of the radical SAM superfamily and contains multiple Fe - S clusters. To characterize the Fe - S clusters in PqqE from Methylobacterium extorquens AM1, Cys residues conserved in the N-terminal signature motif (CX3 CX2 C) and the C-terminal seven-cysteine motif (CX9-15 GX4 CX n CX2 CX5 CX3 CX n C; n  = an unspecified number) were individually or simultaneously mutated into Ser...
December 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/29212734/predictors-of-response-and-survival-in-locally-advanced-adenocarcinoma-of-the-pancreas-following-neoadjuvant-gtx-with-or-without-radiation-therapy
#14
William H Sherman, Elizabeth Hecht, David Leung, Kyung Chu
LESSONS LEARNED: There is no presenting parameter that predicts the success of neoadjuvant therapy for pancreatic cancer.Despite the images on scans following neoadjuvant therapy, all patients should be evaluated, because inflammation following radiation therapy (RT) may overstate the extent of tumor and vascular involvement. BACKGROUND: In patients presenting with locally advanced pancreatic adenocarcinoma deemed unresectable by two pancreatic cancer surgeons, we analyzed presenting tumor size, extent of vascular involvement, tumor markers, response to neoadjuvant gemcitabine (G), docetaxel (T), and capecitabine (X) with or without additional chemoradiotherapy with GX on R0 resection rates (≥2 mm margins), and survival...
January 2018: Oncologist
https://www.readbyqxmd.com/read/29172486/a-stable-isotope-dilution-nanoflow-liquid-chromatography-tandem-mass-spectrometry-assay-for-the-simultaneous-detection-and-quantification-of-glyoxal-induced-dna-cross-linked-adducts-in-leukocytes-from-diabetic-patients
#15
Hauh-Jyun Candy Chen, Ya-Lang Chang, Yi-Chun Teng, Chiung-Fong Hsiao, Tsai-Shiuan Lin
Glyoxal (gx) is a bifunctional electrophile capable of cross-linking DNA. Although it is present in foods and from the environment, endogenous formation of glyoxal occurs through metabolism of carbohydrates and oxidation of lipids and nucleic acids. Plasma concentrations of glyoxal are elevated in in diabetes mellitus patients compared to nondiabetics. The most abundant 2'-deoxyribonucleoside adducts cross-linked by glyoxal are dG-gx-dC, dG-gx-dA, and dG-gx-dG. These DNA cross-links can be mutagenic by damaging the integrity of the DNA structure...
December 19, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29168858/ferromagnetic-coupling-in-copper-benzimidazole-chloride-structural-mass-spectrometry-magnetism-and-dft-studies
#16
Xing-Xing Shi, Yuexing Zhang, Qiu-Jie Chen, Zheng Yin, Xue-Li Chen, Zhenxing Wang, Zhong-Wen Ouyang, Mohamedally Kurmoo, Ming-Hua Zeng
Herein, quasi-square planar CuII (Hmbm)Cl2 (CBC, Hmbm = (1-methyl-1H-benzo[d]imidazol-2-yl)methanol) was arranged in a pseudo orthogonal way to form Cl-bridged chains, and further ππ interactions resulted in distorted hexagonal layers. DFT calculations reveal a bond strength order of Cu-Cl > Cu-O/N ≫ CuCl. ESI-MS data reveal several small fragments from CBC, but oligomeric [Cu], [Cu], and [Cu] for non-zero in-source energies; MS data indicates the occurrence of several chemical processes, viz. splitting of the ligand, oligomerization, and redox reaction of alcohol to aldehyde and CuII to CuI ...
December 21, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/29127731/endoscopic-submucosal-dissection-of-early-gastric-neoplasms-in-the-fornix-using-the-newly-developed-scissor-type-sb-knife-gx
#17
Yuki Sumida, Toshio Kuwai, Sauid Ishaq
No abstract text is available yet for this article.
January 2018: Digestive Endoscopy: Official Journal of the Japan Gastroenterological Endoscopy Society
https://www.readbyqxmd.com/read/29119984/catalytic-fixation-of-atmospheric-carbon-dioxide-by-copper-ii-complexes-of-bidentate-ligands
#18
Sethuraman Muthuramalingam, Themmila Khamrang, Marappan Velusamy, Ramasamy Mayilmurugan
New copper(ii) complexes, [Cu(L1)2 (H2 O)](ClO4 )2 , 1 [L1 = 2-pyridin-2-yl-quinoline], [Cu(L2)2 (H2 O)](ClO4 )2 , 2 [L2 = 2-pyridin-2-yl-quinoxaline], [Cu(L3)2 (H2 O)](ClO4 )2 , 3 [L3 = 6,7-dimethyl-2-pyridin-2-yl-quinoxaline], [Cu(L4)2 (H2 O)](ClO4 )2 , 4 [L4 = 4-phenyl-2-pyridin-2-yl-quinoline] and [Cu(L5)2 (H2 O)](ClO4 )2 , 5 [L5 = 4-phenyl-2-pyridin-2-yl-quinazoline], were synthesized and characterized as catalysts for selective fixation of atmospheric CO2 . The molecular structure of 2 was determined by single-crystal X-ray studies and shown to have an unusual trigonal bipyramid geometry (τ, 0...
November 28, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/29107627/optimal-13-c-labeling-of-glycerol-carbon-source-for-precise-flux-estimation-in-escherichia-coli
#19
Yoshihiro Toya, Shugo Ohashi, Hiroshi Shimizu
Glycerol is a promising carbon source for bio-production and is particularly attractive because it is produced in excess as a biodiesel byproduct. Elucidating the flux distribution of glycerol catabolism would greatly aid metabolic engineering, but (13)C-labeling of glycerol has not yet been optimized for precise flux estimations. In this study, an Escherichia coli wild type strain was aerobically cultured using glycerol as the sole carbon source. [1,3-(13)C], [2-(13)C], and [U-(13)C] glycerols were independently mixed with an equal amount of naturally labeled glycerol; these mixtures were used as (13)C-labeled substrates, and flux distributions during exponential growth were estimated based on (13)C-enrichment of proteinogenic amino acids...
October 26, 2017: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/29094805/synthesis-of-naphthyridine-dimers-with-conformational-restriction-and-binding-to-dna-and-rna
#20
Kazuhiko Nakatani, Nozomi Natsuhara, Yuki Mori, Sanjukta Mukherjee, Bimolendu Das, Asako Murata
One of the important determinants in the efficiency of a molecular interaction is the necessity for conformational changes in host and/or guest molecules upon binding. In small-molecule interactions with nucleic acids, conformational changes on both molecules are often involved, especially in intercalating binding. Mismatch binding ligands (MBLs) we described here consist of two heterocycles that predominantly exist in one conformation, so it is of interest to determine if such molecules can bind to any DNA and RNA structures...
December 5, 2017: Chemistry, An Asian Journal
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