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https://www.readbyqxmd.com/read/28350969/mechanisms-of-spontaneous-pacing-sa-nodal-cells-neonatal-cardiomyocytes-and-human-stem-cell-derived-cardiomyocytes
#1
Martin Morad, Xiaohua Zhang
The sino-atrial node is the primary site from which the mammalian heart is paced, but the mechanisms underlying the pacemaking still remain clouded. It is generally believed that the hyperpolarization-activated current I<sub><i>f</i></sub>, encoded by Hyperpolarization-activated cyclic nucleotide-gated (HCN) genes, contributes significantly to pacing, which in tandem with inward current generated by efflux of Ca<sup>2+</sup> via the Na<sup>+</sup>-Ca<sup>2+</sup> exchanger (NCX), resulting from the released Ca<sup>2+</sup>, mediates the diastolic depolarization...
March 28, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28350716/movement-strategies-among-groups-of-chronic-ankle-instability-coper-and-control
#2
S Jun Son, Hyunsoo Kim, Mattew K Seeley, J Ty Hopkins
INTRODUCTION: Comprehensive evaluation of movement strategies during functional movement is a difficult undertaking. Because of this challenge, studied movements have been over simplified. Furthermore, evaluating movement strategies at only a discrete time point(s) provide limited insight into how movement strategies may change or adapt in chronic ankle instability (CAI) patients. This study aimed to identify abnormal movement strategies in individuals with a history of ankle sprain injury during a sports maneuver compared to healthy controls...
March 27, 2017: Medicine and Science in Sports and Exercise
https://www.readbyqxmd.com/read/28350665/moderate-intensity-intermittent-external-volume-expansion-optimizes-the-soft-tissue-response-in-a-murine-model
#3
Giorgio Giatsidis, Liying Cheng, Federico Facchin, Anthony Haddad, Jorge Lujan-Hernandez, Luca Lancerotto, Christoph Gunther Nabzdyk, Hajime Matsumine, Dennis P Orgill
BACKGROUND: Intermittent external volume expansion using suction enhances the vascular network of soft tissues, possibly increasing fat graft survival. However, the optimal kinetics of application have not been determined. Based on their previous experience, the authors hypothesized that moderate-intensity intermittent external volume expansion application may further enhance both the angiogenic and adipogenic potential. METHODS: Fifty 12-week-old wild-type mice were assigned to five experimental groups (n = 10 per group) and underwent five different intermittent applications of external volume expansion (i...
April 2017: Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/28350474/detachment-of-membrane-bound-virions-by-competitive-ligand-binding-induced-receptor-depletion
#4
Nagma Parveen, Stephan Block, Vladimir P Zhdanov, Gustaf E Rydell, Fredrik Höök
Multivalent receptor-mediated interactions between virions and a lipid membrane can be weakened using competitive non-pathogenic ligand binding. In particular, the subsequent binding of such ligands can induce detachment of bound virions, a phenomena of crucial relevance for the development of new antiviral drugs. Focusing on the simian virus 40 (SV40) and recombinant cholera toxin B subunit (rCTB), and using (monosialotetrahexosyl)ganglioside (GM1) as their common receptor in a supported lipid bilayer (SLB), we present the first detailed investigation of this phenomenon by employing the quartz crystal microbalance with dissipation (QCM-D) and total internal reflection fluorescence (TIRF) microscopy assisted 2D single particle tracking (SPT) techniques...
March 28, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28350453/diazaphenoxazines-and-diazaphenothiazines-synthesis-of-the-correct-isomers-reveals-they-are-highly-reactive-radical-trapping%C3%A2-antioxidants
#5
Evan A Haidasz, Derek A Pratt
The preparation of 2,4-diazaphenothiazines and 2,4-diazaphenoxazines via a copper-catalyzed intramolecular amination is described. Literature approaches which utilize easily accessed (2'-aminophenyl) 4-pyri(mi)dyl sulfides undergo a Smiles rearrangement that gives rise to the 1,3-diaza derivatives instead, confirmed by X-ray crystallography. Inversion of the polarity of the cyclization avoids the rearrangement and affords the desired products. Preliminary kinetic studies suggest that 2,4-diazaphenothiazines and diazaphenoxazines, but not the 1,3-diaza isomers, are remarkably potent radical-trapping antioxidants...
March 28, 2017: Organic Letters
https://www.readbyqxmd.com/read/28350434/stepwise-synthesis-of-metal-organic-frameworks
#6
Mathieu Bosch, Shuai Yuan, William Rutledge, Hong-Cai Zhou
Metal-organic frameworks (MOFs) are a category of porous materials that offer unparalleled control over their surface areas (demonstrated as higher than for any other material), pore characteristics, and functionalization. This allows them to be customized for exceptional performance in a wide variety of applications, most commonly including gas storage and separation, drug delivery, luminescence, or heterogeneous catalysis. In order to optimize biomimicry, controlled separations and storage of small molecules, and detailed testing of structure-property relationships, one major goal of MOF research is "rational design" or "pore engineering", or precise control of the placement of multiple functional groups in pores of chosen sizes and shapes...
March 28, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28346871/synthesis-in-vitro-evaluation-and-molecular-docking-studies-of-novel-amide-linked-triazolyl-glycoconjugates-as-new-inhibitors-of-%C3%AE-glucosidase
#7
Shyam Ji Gupta, Samrat Dutta, Rahul L Gajbhiye, Parasuraman Jaisankar, Asish Kumar Sen
A series of N-substituted amide linked triazolyl β-d-glucopyranoside derivatives (4a-l) were synthesized and their in vitro inhibitory activity against yeast α-glucosidase enzyme [EC.3.2.1.20] was assessed. Compounds 4e (IC50=156.06μM), 4f (IC50=147.94μM), 4k (IC50=127.71μM) and 4l (IC50=121.33μM) were identified as the most potent inhibitors for α-glucosidase as compared to acarbose (IC50=130.98μM) under the same in vitro experimental conditions. Kinetic study showed that both 4e and 4f inhibit the enzyme in a competitive manner with p-nitrophenyl α-d-glucopyranoside as substrate...
March 18, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/28346784/structure-determination-of-mycobacterium-tuberculosis-serine-protease-hip1-rv2224c
#8
Jacqueline Lara Naffin-Olivos, Andrew Daab, Andre White, Nathan Eric Goldfarb, Amy C Milne, Dali Liu, Jacqueline Baikovitz, Ben M Dunn, Jyothi Rengarajan, Gregory A Petsko, Dagmar Ringe
The Mycobacterium tuberculosis (Mtb) serine protease Hip1 (Hydrolase important for pathogenesis; Rv2224c) promotes tuberculosis (TB) pathogenesis by impairing host immune responses through proteolysis of a protein substrate, Mtb GroEL2. The cell surface localization of Hip1 and its immunomodulatory functions make Hip1 a good drug target for new adjunctive immune therapies for TB. Here we report the crystal structure of Hip1 to a resolution of 2.6 Å and the kinetic studies of the enzyme against model substrates and the protein GroEL2...
March 27, 2017: Biochemistry
https://www.readbyqxmd.com/read/28346548/kinetics-of-light-induced-ordering-and-deformation-in-lc-azobenzene-containing-materials
#9
Vladimir Toshchevikov, Tatiana Petrova, Marina Saphiannikova
Azobenzene-containing smart materials are able to transform the energy of light into directional mechanical stress. We develop a theory of time-dependent light-induced ordering and deformation in azobenzene materials starting from the kinetic equations of photoisomerization. The liquid crystalline (LC) interactions between rod-like trans-isomers are taken into account. Angular selectivity of the photoisomerization known as an "angular hole burning" or the Weigert effect leads to the light-induced ordering and deformation of the azobenzene materials...
March 27, 2017: Soft Matter
https://www.readbyqxmd.com/read/28346390/the-effect-and-mechanism-of-transdermal-penetration-enhancement-of-fu-s-cupping-therapy-new-physical-penetration-technology-for-transdermal-administration-with-traditional-chinese-medicine-tcm-characteristics
#10
Wei-Jie Xie, Yong-Ping Zhang, Jian Xu, Xiao-Bo Sun, Fang-Fang Yang
BACKGROUND: In this paper, a new type of physical penetration technology for transdermal administration with traditional Chinese medicine (TCM) characteristics is presented. Fu's cupping therapy (FCT), was established and studied using in vitro and in vivo experiments and the penetration effect and mechanism of FCT physical penetration technology was preliminarily discussed. METHODS: With 1-(4-chlorobenzoyl)-5-methoxy-2-methylindole-3-ylacetic acid (indomethacin, IM) as a model drug, the establishment of high, medium, and low references was completed for the chemical permeation system via in vitro transdermal tests...
March 27, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28346355/characterization-of-active-anthocyanin-degradation-in-the-petals-of-rosa-chinensis-and-brunfelsia-calycina-reveals-the-effect-of-gallated-catechins-on-pigment-maintenance
#11
Honghui Luo, Shuangfan Deng, Wei Fu, Xin Zhang, Xuelian Zhang, Zhaoqi Zhang, Xuequn Pang
Anthocyanin degradation decreases ornamental or nutritional values of horticultural products. To investigate factors that may influence colour change in flower development, anthocyanin degradation was compared between the flowers of Brunfelsia calycina and Rosa chinensis, which show rapid and slow degradation, respectively. In-gel activity assays, high performance liquid chromatography (HPLC) analysis of tannins, enzyme kinetics measurement and immune-detection of anthocyanin degradation related-perioxidases (PODs) were carried out for the comparison...
March 25, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28346096/a-novel-multiparametric-drug-scoring-method-for-high-throughput-screening-of-3d-multicellular-tumor-spheroids-using-the-celigo-image-cytometer
#12
Scott Cribbes, Sarah Kessel, Scott McMenemy, Jean Qiu, Leo Li-Ying Chan
Three-dimensional (3D) tumor models have been increasingly used to investigate and characterize cancer drug compounds. The ability to perform high-throughput screening of 3D multicellular tumor spheroids (MCTS) can highly improve the efficiency and cost-effectiveness of discovering potential cancer drug candidates. Previously, the Celigo Image Cytometer has demonstrated a novel method for high-throughput screening of 3D multicellular tumor spheroids. In this work, we employed the Celigo Image Cytometer to examine the effects of 14 cancer drug compounds on 3D MCTS of the glioblastoma cell line U87MG in 384-well plates...
January 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28346093/a-label-free-continuous-fluorescence-based-assay-for-monitoring-ornithine-decarboxylase-activity-with-a-synthetic-putrescine-receptor
#13
Mohamed Nilam, Philip Gribbon, Jeanette Reinshagen, Kathrin Cordts, Edzard Schwedhelm, Werner M Nau, Andreas Hennig
Polyamines play an important role in cell growth, differentiation, and cancer development, and the biosynthetic pathway of polyamines is established as a drug target for the treatment of parasitic diseases, neoplasia, and cancer chemoprevention. The key enzyme in polyamine biosynthesis is ornithine decarboxylase (ODC). We report herein an analytical method for the continuous fluorescence monitoring of ODC activity based on the supramolecular receptor cucurbit[6]uril (CB6) and the fluorescent dye trans-4-[4-(dimethylamino)styryl]-1-methylpyridinium iodide (DSMI)...
January 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28345911/subtle-microwave-induced-overheating-effects-in-an-industrial-de-methylation-reaction-and-their-direct-use-in-the-development-of-an-innovative-microwave-reactor
#14
Mario De Bruyn, Vitaliy L Budarin, Guido S J Sturm, Georgios D Stefanidis, Marilena Radoiu, Andrzej Stankiewicz, Duncan J Macquarrie
A systematic study of the conventional and microwave (MW) kinetics of an industrially relevant demethylation reaction is presented. In using industrially relevant reaction conditions the dominant influence of the solvent on the MW energy dissipation is avoided. Below the boiling point, the effect of MWs on the activation energy Ea and k0 is found non-existent. Interestingly under reflux conditions the microwave heated (MWH) reaction displays very pronounced zero order kinetics, displaying a much higher reaction rate than observed for the conventionally thermal heated (CTH) reaction...
March 27, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28345900/fluorescence-and-radio-labeling-of-lys-4-nle-17-30-hpp-yields-molecular-tools-for-the-npy-y4-receptor
#15
Stefanie Dukorn, Timo Littmann, Max Keller, Kilian Konrad Kuhn, Chiara Cabrele, Paul Baumeister, Günther Bernhardt, Armin Buschauer
The neuropeptide Y (NPY) Y4 receptor (Y4R) is involved in energy homeostasis and considered as a potential drug target for the treatment of obesity. Only a few molecular tools, i. e., radiolabeled and fluorescent ligands, for the investigation of the Y4R were reported. Previously, [Lys(4)]hPP proved to be an appropriate full-length PP analog to prepare a fluorescent ligand by derivatization at the ε-amino group. To preclude oxidation upon long-term storage, we replaced the two methionine residues in [Lys(4)]hPP by norleucine and prepared the corresponding [(3)H]propionylated ([(3)H]12) and cyanine labeled (13) peptides, which were characterized and compared with a set of reference compounds in binding (Y1, Y2, Y4 and Y5 receptors) and functional (luciferase gene reporter, β-arrestin-1, -2) Y4R assays...
March 27, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28345899/ammonia-borane-dehydrogenation-catalyzed-by-%C3%AE%C2%BA-4-ep3-co-h-ep3-e-ch2ch2pph2-3-e-n-p-and-h2-evolution-from-their-interaction-with-nh-acids
#16
Stefano Todisco, Lapo Luconi, Giuliano Giambastiani, Andrea Rossin, Maurizio Peruzzini, Igor E Golub, Oleg A Filippov, Natalia V Belkova, Elena S Shubina
Two Co(I) hydrides containing the tripodal polyphosphine ligand EP3, (κ(4)-EP3)Co(H) [E(CH2CH2PPh2)3; E = N (1), P (2)], have been exploited as ammonia borane (NH3BH3, AB) dehydrogenation catalysts in THF solution at T = 55 °C. The reaction has been analyzed experimentally through multinuclear ((11)B, (31)P{(1)H}, (1)H) NMR and IR spectroscopy, kinetic rate measurements, and kinetic isotope effect (KIE) determination with deuterated AB isotopologues. Both complexes are active in AB dehydrogenation, albeit with different rates and efficiency...
March 27, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28345897/a-smart-molecule-for-selective-sensing-of-nitric-oxide-conversion-of-no-to-hsno-relevance-of-biological-hsno-formation
#17
Abu Saleh Musha Islam, Rahul Bhowmick, Kaberi Pal, Atul Katarkar, Keya Chaudhuri, Mahammad Ali
A smart molecule, QT490, containing thiosemicarbazide moiety acts as a highly selective turn-on in vitro NO sensor through the unprecedented NO-induced transformation of thiosemicarbazide moiety to 1,3,4-oxadiazole heterocycle with the concomitant release of HSNO, thereby eliminating any interference from various endogenous biomolecules including dehydroascorbic acid, ascorbic acid, etc. The kinetic studies of the reactions between QT490 and NO provide a mechanistic insight into formation of HSNO/RSNO from the reaction between H2S/RSH and NO in the biological system...
March 27, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28345895/asymmetric-anchoring-is-required-for-efficient-%C3%AE-loop-opening-and-closing-in-cytosolic-phosphoenolpyruvate-carboxykinase
#18
Danica Cui, Aron Broom, Matthew J Mcleod, Elizabeth M Meiering, Todd Holyoak
Mobile Ω-loops play essential roles in the function of many enzymes. Here we investigated the importance of a residue lying outside of the mobile Ω-loop element in the catalytic function of an H477R variant of cPEPCK using crystallographic, kinetic, and computational analysis. The crystallographic data suggest that efficient transitioning of the Ω-loop to the closed conformation requires stabilization of the N-terminus of the loop through contacts between R461 and E588. In contrast, the C-terminal end of the Ω-loop undergoes changing interactions with the enzyme body through contacts between H477 at the C-terminus of the loop and E591 located on the enzyme body...
March 27, 2017: Biochemistry
https://www.readbyqxmd.com/read/28345889/ape1-accelerates-turnover-of-hogg1-by-preventing-retrograde-binding-to-the-abasic-site-product
#19
Alexandre Esadze, Gaddiel Rodriguez, Shannen Lee Cravens, James T Stivers
A major product of oxidative DNA damage is 8-oxoguanine. In humans, 8-oxoguanine DNA Glycosylase (hOGG1) facilitates removal of these lesions, producing an abasic (AP) site in the DNA that is subsequently incised by AP-endonuclease 1 (APE1). APE1 stimulates turnover of several glycosylases by accelerating rate-limiting product release. However, there have been conflicting accounts of whether hOGG1 follows a similar mechanism. In pre-steady state kinetic measurements, we found that addition of APE1 had no effect on the rapid burst phase of 8-oxoguanine excision by hOGG1, but accelerated steady-state turnover (kcat) by ~10-fold...
March 27, 2017: Biochemistry
https://www.readbyqxmd.com/read/28345888/influence-of-ring-strain-and-bond-polarization-on-the-ring-expansion-of-phosphorus-homocycles
#20
Saurabh S Chitnis, Rebecca A Musgrave, Hazel A Sparkes, Natalie E Pridmore, Vincent T Annibale, Ian Manners
Heterolytic cleavage of homoatomic bonds is a challenge, as it requires separation of opposite charges. Even highly strained homoatomic rings (e.g., cyclopropane and cyclobutane) are kinetically stable and do not react with nucleophiles or electrophiles. In contrast, cycloalkanes bearing electron-donating/withdrawing substituents on adjacent carbons have polarized C-C bonds and undergo numerous heterolytic ring-opening and expansion reactions. Here we show that upon electrophile activation phosphorus homocycles exhibit analogous reactivity, which is modulated by the amount of ring strain and extent of bond polarization...
March 27, 2017: Inorganic Chemistry
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