Search results for "Mechanism"
showing 10 items of 1835 documents
Bioactivation of the Fungal Phytotoxin 2,5-Anhydro-D-glucitol by Glycolytic Enzymesisan Essential Component of itsMechanism of Action
2002
An isolate of Fusarium solani, NRRL 18883, produces the natural phytotoxin 2,5-anhydro-ᴅ-glucitol (AhG). This fungal metabolite inhibited the growth of roots (I50 of 1.6 mᴍ), butit did nothave any in vitro inhibitory activity. The mechanism of action of AhG requires enzymatic phosphorylation by plant glycolytic kinases to yield AhG-1,6-bisphosphate (AhG-1,6- bisP), an inhibitor of Fru-1,6-bisP aldolase. AhG-1,6-bisP had an I50 value of 570 μᴍ on aldolase activity, and it competed with Fru-1,6-bisP for the catalytic site on the enzyme, with a Ki value of 103 μᴍ. The hydroxyl group on the anomeric carbon of Fru-1,6-bisP is required for the formation of an essential covalent bond to ζ amino fu…
In vitro fusion of phagosomes with different endocytic organelles from J774 macrophages.
1998
We describe novel biochemical and electron microscopy assays to investigate in vitro fusion of latex bead phagosomes with three different endocytic organelle fractions from J774 macrophages. After formation, early phagosomes fuse avidly with early and late endosomes and for a longer period of time with lysosomes, but they subsequently become fusion-incompetent. The fusion of early, but not late, phagosomes with all three endocytic fractions could be significantly stimulated by Rab5. In contrast to other cell types investigated, this Rab is uniquely enriched on both early and late endosomes in J774 macrophages. Moreover, exogenous Rab5 stimulates homotypic fusion between both sets of organel…
A Molecular Electron Density Theory Study of the Reactivity of Azomethine Imine in [3+2] Cycloaddition Reactions
2017
The electronic structure and the participation of the simplest azomethine imine (AI) in [3+2] cycloaddition (32CA) reactions have been analysed within the Molecular Electron Density Theory (MEDT) using DFT calculations at the MPWB1K/6-311G(d) level. Electron localisation function (ELF) topological analysis reveals that AI has a pseudoradical structure, while the conceptual DFT reactivity indices characterise this TAC as a moderate electrophile and a good nucleophile. The non-polar 32CA reaction of AI with ethylene takes place through a one-step mechanism with low activation energy, 5.3 kcal/mol-1. A bonding evolution theory (BET) study indicates that this reaction takes place through a non-…
Editorial: Understanding Gamma Delta T Cell Multifunctionality - Towards Immunotherapeutic Applications.
2020
Introduction: gd T cells have been characterized by the expression of a gd T cell receptor (TCR).When the gd TCR and the corresponding ab TCR were first discovered it was assumed that the corresponding cell types were likely to be functionally very similar. However, some 30 years later, we have realized that they are not. Unlike ab T cells, gd T cells (i) sense target antigens independent of MHC molecules; (ii) display NK-cell like innate reactivities, including killing of infected cells as well as microbes; (iii) are able to take up large particulates, including bacteria, and (iv) can act as professional antigen presenting cells. The “stress sensing” abilities of gd T cells have led to a g…
Mildronate: An Antiischemic Drug for Neurological Indications
2005
Mildronate (3-(2,2,2-trimethylhydrazinium)propionate; MET-88; meldonium, quaterine) is an antiischemic drug developed at the Latvian Institute of Organic Synthesis. Mildronate was designed to inhibit carnitine biosynthesis in order to prevent accumulation of cytotoxic intermediate products of fatty acid beta-oxidation in ischemic tissues and to block this highly oxygen-consuming process. Mildronate is efficient in the treatment of heart ischemia and its consequences. Extensive evaluation of pharmacological activities of mildronate revealed its beneficial effect on cerebral circulation disorders and central nervous system (CNS) functions. The drug is used in neurological clinics for the trea…
An overview on chemical structures as ΔF508-CFTR correctors
2019
Deletion of phenylalanine at position 508 (F508del) in the CFTR protein, is the most common mutation causing cystic fibrosis (CF). F508del causes misfolding and rapid degradation of CFTR protein a defect that can be targeted with pharmacological agents termed “correctors”. Correctors belong to various chemical classes but are generally small molecules based on nitrogen sulfur or oxygen heterocycles. The mechanism of action of correctors is generally unknown but there is experimental evidence that some of them can directly act on mutant CFTR improving folding and stability. Here we overview the characteristics of the various F508del correctors described so far to obtain indications on key ch…
Role of the functional group in n-octydimethylsilanes in the synthesis of C8 reversed-phase silica packings for high-performance liquid chromatography
1986
Abstract C8 reversed-phase packings have been sysnthesised by reaction of a 25-nm pore-size high-performance liquid chromatographic silica (10 μm, as(BET) = 297 m2 g-1) with 2,4-lutidine as base and dichloromethane and N,N-dimethylflormamide as solvents, or without solvents and with the following silanes: n-octyldimenthylchlorosilane (C8-Cl), n-octyldimethylhydroxysilane (C8-OH), n-octyldimethylmethoxysilane (C8-OCH3), n-octyldimethylethoxysilane (C8-OC2H5), n-octyldimethyl(dimethylamino) silane [C8-N(CH3)2], n-octyldimethyl(trifluoroacetoxy)silane (C8- OCOCF3), and bis-(n-octyldimethylsiloxane) (C8-O-C8). C8-Cl, C8-OH and C8-OCH3 each form a reactive intermediate with 2,4-lutidine, favouri…
Catalytic Reaction Mechanism in Native and Mutant Catechol- O-methyltransferase from the Adaptive String Method and Mean Reaction Force Analysis.
2018
Catechol- O-methyltransferase is an enzyme that catalyzes the methylation reaction of dopamine by S-adenosylmethionine, increasing the reaction rate by almost 16 orders of magnitude compared to the reaction in aqueous solution. Here, we combine the recently introduced adaptive string method and the mean reaction force method, in combination with the structural and electronic descriptors to characterize the reaction mechanism. The catalytic effect of the enzyme is addressed by the comparison of the reaction in the human wild-type enzyme, in the less effective Y68A mutant, and in aqueous solution. The influence of these different environments at different stages of the chemical process and th…
An investigation of thermal behaviour of brake disk pad assembly with Ansys
2021
Abstract The brake disk is a key part of the braking mechanism, the task of it is to slow or stop the vehicle's wheels, on the one side, while the heat produced during the process is dissipated. In this regard, the brake pads are pressed by mechanical strength on the surface of the brake disks. This study aims to develop a model of a disk brake by use of CATIA V5, on the model, finite element analysis (FEA) done by ANSYS 19 then compare it to the findings gained by the original tests. A computational thermo-mechanical study was conducted on this research by use of ANSYS software for disk brake mounting inside a hydraulic brake system. This study is designed to provide insight into the heat …
P0926 : Representation of human non-alcoholic fatty liver disease in murine models
2015
COX-2 enhances insulin signaling. Finally, the relationship between COX-2 and the miRNAs was confirmed in NAS. Conclusions: COX-2 represses the expression of miRNAs implicated in the insulin signaling pathway via a PI3K/p300-dependent upregulation of DDX5, and by modulating the activity of the Drosha complex. Our study proposes a novel miRNA-dependent mechanism through which COX-2 promotes insulin signaling in liver cells.