On denial: An initial reaction; on trusting and on caring

1985 ◽  
Author(s):  
Robin St. Anthony
Keyword(s):  
Initial Reaction

Effect of Depolymerized Holothurian Glycosaminoglycan (DHG) on Tissue Factor Pathway Inhibitor: In Vitro and In Vivo Studies

1997 ◽  
Vol 78 (02) ◽  
pp. 864-870 ◽  
Author(s):  
Hideki Nagase ◽  
Kei-ichi Enjyoji ◽  
Yu-ichi Kamikubo ◽  
Keiko T Kitazato ◽  
Kenji Kitazato ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Tissue Factor Pathway Inhibitor ◽  
Factor Xa ◽  
Free Form ◽  
Initial Reaction ◽  
Extrinsic Pathway ◽  
Factor Xa Inhibition ◽  
Tissue Factor Pathway

SummaryDepolymerized holothurian glycosaminoglycan (DHG) is a glycosaminoglycan extracted from the sea cucumber Stichopus japonicusSelenka. In previous studies, we demonstrated that DHG has antithrombotic and anticoagulant activities that are distinguishable from those of heparin and dermatan sulfate. In the present study, we examined the effect of DHG on the tissue factor pathway inhibitor (TFPI), which inhibits the initial reaction of the tissue factor (TF)-mediated coagulation pathway. We first examined the effect of DHG on factor Xa inhibition by TFPI and the inhibition of TF-factor Vila by TFPI-factor Xa in in vitro experiments using human purified proteins. DHG increased the rate of factor Xa inhibition by TFPI, which was abolished either with a synthetic C-terminal peptide or with a synthetic K3 domain peptide of TFPI. In contrast, DHG reduced the rate of TF-factor Vila inhibition by TFPI-factor Xa. Therefore, the effect of DHG on in vitroactivity of TFPI appears to be contradictory. We then examined the effect of DHG on TFPI in cynomolgus monkeys and compared it with that of unfractionated heparin. DHG induced an increase in the circulating level of free-form TFPI in plasma about 20-fold when administered i.v. at 1 mg/kg. The prothrombin time (PT) in monkey plasma after DHG administration was longer than that estimated from the plasma concentrations of DHG. Therefore, free-form TFPI released by DHG seems to play an additive role in the anticoagulant mechanisms of DHG through the extrinsic pathway in vivo. From the results shown in the present work and in previous studies, we conclude that DHG shows anticoagulant activity at various stages of coagulation reactions, i.e., by inhibiting the initial reaction of the extrinsic pathway, by inhibiting the intrinsic Xase, and by inhibiting thrombin.

The Kinetics of Inhibition of the Action of Thrombin by the Fibrinopeptides Formed during the Clotting of Fibrinogen

1966 ◽  
Vol 16 (01/02) ◽  
pp. 277-295 ◽  
Author(s):  
A Silver ◽  
M Murray
Keyword(s):  
Amino Acids ◽  
Competitive Inhibition ◽  
Amorphous Material ◽  
Peptide Bond ◽  
Initial Reaction ◽  
Reaction Products ◽  
Coagulation Mechanism ◽  
Kinetics Of ◽  
Kinetics Of Inhibition ◽  
Burk Plot

SummaryVarious investigators have separated the coagulation products formed when fibrinogen is clotted with thrombin and identified fibrinopeptides A and B. Two other peaks are observed in the chromatogram of the products of coagulation, but these have mostly been dismissed by other workers. They have been identified by us as amino acids, smaller peptides and amorphous material (37). We have re-chromatographed these peaks and identified several amino acids. In a closed system of fibrinogen and thrombin, the only reaction products should be fibrin and peptide A and peptide B. This reasoning has come about because thrombin has been reported to be specific for the glycyl-arginyl peptide bond. It is suggested that thrombin also breaks other peptide linkages and the Peptide A and Peptide B are attacked by thrombin to yield proteolytic products. Thrombin is therefore probably not specific for the glycyl-arginyl bond but will react on other linkages as well.If the aforementioned is correct then the fibrinopeptides A and B would cause an inhibition with the coagulation mechanism itself. We have shown that an inhibition does occur. We suggest that there is an autoinhibition to the clotting mechanism that might be a control mechanism in the human body.The experiment was designed for coagulation to occur under controlled conditions of temperature and time. Purified reactants were used. We assembled an apparatus to record visually the speed of the initial reaction, the rate of the reaction, and the density of the final clot formed after a specific time.The figures we derived made available to us data whereby we could calculate and plot the information to show the mechanism and suggest that such an inhibition does exist and also further suggest that it might be competitive.In order to prove true competitive inhibition it is necessary to fulfill the criteria of the Lineweaver-Burk plot. This has been done. We have also satisfied other criteria of Dixon (29) and Bergman (31) that suggest true competitive inhibition.

Iterative Supervised Principal Component Analysis-Driven Ligand Design for Regioselective Ti-Catalyzed Pyrrole Synthesis

2020 ◽  
Author(s):  
Xin Yi See ◽  
Benjamin Reiner ◽  
Xuelan Wen ◽  
T. Alexander Wheeler ◽  
Channing Klein ◽  
...  
Keyword(s):  
Principal Component Analysis ◽  
De Novo ◽  
Principal Component ◽  
Component Analysis ◽  
Catalyst Design ◽  
Data Driven ◽  
Initial Reaction ◽  
Training Set ◽  
Reaction Conditions ◽  
Component Loadings

<div> <div> <div> <p>Herein, we describe the use of iterative supervised principal component analysis (ISPCA) in de novo catalyst design. The regioselective synthesis of 2,5-dimethyl-1,3,4-triphenyl-1H- pyrrole (C) via Ti- catalyzed formal [2+2+1] cycloaddition of phenyl propyne and azobenzene was targeted as a proof of principle. The initial reaction conditions led to an unselective mixture of all possible pyrrole regioisomers. ISPCA was conducted on a training set of catalysts, and their performance was regressed against the scores from the top three principal components. Component loadings from this PCA space along with k-means clustering were used to inform the design of new test catalysts. The selectivity of a prospective test set was predicted in silico using the ISPCA model, and only optimal candidates were synthesized and tested experimentally. This data-driven predictive-modeling workflow was iterated, and after only three generations the catalytic selectivity was improved from 0.5 (statistical mixture of products) to over 11 (> 90% C) by incorporating 2,6-dimethyl- 4-(pyrrolidin-1-yl)pyridine as a ligand. The successful development of a highly selective catalyst without resorting to long, stochastic screening processes demonstrates the inherent power of ISPCA in de novo catalyst design and should motivate the general use of ISPCA in reaction development. </p> </div> </div> </div>

Autosomal Recessive Non-syndromic Keratoconus: Homozygous Frameshift Variant in the Candidate Novel Gene GALNT14

2019 ◽  
Vol 19 (9) ◽  
pp. 683-687 ◽  
Author(s):  
Tawfiq Froukh ◽  
Ammar Hawwari
Keyword(s):  
Strong Evidence ◽  
Autosomal Recessive ◽  
Eye Diseases ◽  
Initial Reaction ◽  
Genetic Contribution ◽  
Loss Of Function ◽  
Consanguineous Family ◽  
Truncated Protein ◽  
Threonine Residue ◽  
Whole Exome

Background: Keratoconus (KC) is usually bilateral, noninflammatory progressive corneal ectasia in which the cornea becomes progressively thin and conical. Despite the strong evidence of genetic contribution in KC, the etiology of KC is not understood in most cases. Methods: In this study, we used whole-exome sequencing to identify the genetic cause of KC in two sibs in a consanguineous family. The Homozygous frameshift variant NM_001253826.1:c.60delC;p.Leu21Cysfs*6 was identified in the gene Nacetylgalactosaminyltransferase 14 (GALNT14). The variant does not exist in all public databases neither in our internal exome database. Moreover, no database harbours homozygous loss of function variants in the candidate gene. Result: GALNT14 catalyses the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D- galactosamine residue to a serine or threonine residue on target proteins especially Mucins. Conclusion: As alterations of mucin’s glycosylation are linked to a number of eye diseases, we demonstrate in this study an association between the truncated protein GALNT14 and KC.

scholarly journals Renal sodium-potassium adenosine triphosphatase. Optical localization and x-ray microanalysis.

1975 ◽  
Vol 23 (11) ◽  
pp. 828-839 ◽  
Author(s):  
R Beeuwkes ◽  
S Rosen
Keyword(s):  
Atpase Activity ◽  
Electron Probe ◽  
Sequential Analysis ◽  
Relative Sensitivity ◽  
Initial Reaction ◽  
Initial Product ◽  
Sodium Potassium ◽  
Nitrophenyl Phosphate ◽  
Hydrolysis Of ◽  
Convoluted Tubules

The distribution of sodium-potassium adenosine triposphatase (Na-K-ATPase) activity in kidney sections has been studied by a method based on the hydrolysis of p-nitrophenyl phosphate in alkaline medium containing dimethyl sulfoxide. The products at each stage in the reaction sequence have been subjected to electron probe microanalysis. The initial product was identified as a mixture of KMgPO4 and Mg(PO4)2, and sequential analysis demonstrated the linearity of conversion of this product to a visible form. In human, rabbit and rat kidneys the distribution of activity was found to be essentially identical, with highest levels located in thick ascending limbs and distal convoluted tubules. The initial reaction was completely potassium dependent and was inhibited by ouabain in concentrations reflecting the relative sensitivity of microsomal Na-K-ATPase in each species. Measurement of initial product phosphorus by means of the electron probe is presented as a practical technique for direct quantitation of Na-K-ATPase activity in identified tubule segments.

scholarly journals Promising Immobilization of Industrial-Class Phospholipase A1 to Attain High-Yield Phospholipids Hydrolysis and Repeated Use with Optimal Water Content in Water-in-Oil Microemulsion Phase

2021 ◽  
Vol 11 (4) ◽  
pp. 1456
Author(s):  
Yusuke Hayakawa ◽  
Ryoichi Nakayama ◽  
Norikazu Namiki ◽  
Masanao Imai
Keyword(s):  
Water Content ◽  
Reaction Rate ◽  
Enzyme Reaction ◽  
Initial Reaction Rate ◽  
Industrial Applications ◽  
Molar Ratio ◽  
High Yield ◽  
Initial Reaction ◽  
Phospholipase A1 ◽  
Repeated Use

In this study, we maximized the reactivity of phospholipids hydrolysis with immobilized industrial-class phospholipase A1 (PLA1) at the desired water content in the water-in-oil (W/O) microemulsion phase. The optimal hydrophobic-hydrophilic condition of the reaction media in a hydrophobic enzyme reaction is critical to realize the maximum yields of enzyme activity of phospholipase A1. It was attributed to enzymes disliking hydrophobic surroundings as a special molecular structure for reactivity. Immobilization of PLA1 was successfully achieved with the aid of a hydrophobic carrier (Accurel MP100) combination with the treatment using glutaraldehyde. The immobilized yield was over 90% based on simple adsorption. The hydrolysis reaction was kinetically investigated through the effect of glutaraldehyde treatment of carrier and water content in the W/O microemulsion phase. The initial reaction rate increased linearly with an increasing glutaraldehyde concentration and then leveled off over a 6% glutaraldehyde concentration. The initial reaction rate, which was predominantly driven by the water content in the organic phase, changed according to a typical bell-shaped curve with respect to the molar ratio of water to phospholipid. It behaved in a similar way with different glutaraldehyde concentrations. After 10 cycles of repeated use, the reactivity was well sustained at 40% of the initial reaction rate and the creation of the final product. Accumulated yield after 10 times repetition was sufficient for industrial applications. Immobilized PLA1 has demonstrated potential as a biocatalyst for the production of phospholipid biochemicals.

scholarly journals Time-resolved transcriptional profiling of Trichinella-infected murine myocytes helps to elucidate host–pathogen interactions in the muscle stage

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Xiaoxiang Hu ◽  
Xiaolei Liu ◽  
Chen Li ◽  
Yulu Zhang ◽  
Chengyao Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Biology ◽  
Trichinella Spiralis ◽  
Expression Patterns ◽  
Muscle Cells ◽  
Host Cells ◽  
Initial Reaction ◽  
Global Changes ◽  
Mammalian Skeletal Muscle ◽  
Time Resolved

Abstract Background Parasites of the genus Trichinella are the pathogenic agents of trichinellosis, which is a widespread and severe foodborne parasitic disease. Trichinella spiralis resides primarily in mammalian skeletal muscle cells. After invading the cells of the host organism, T. spiralis must elude or invalidate the host’s innate and adaptive immune responses to survive. It is necessary to characterize the pathogenesis of trichinellosis to help to prevent the occurrence and further progression of this disease. The aims of this study were to elucidate the mechanisms of nurse cell formation, pathogenesis and immune evasion of T. spiralis, to provide valuable information for further research investigating the basic cell biology of Trichinella-infected muscle cells and the interaction between T. spiralis and its host. Methods We performed transcriptome profiling by RNA sequencing to identify global changes at 1, 3, 7, 10 and 15 days post-infection (dpi) in gene expression in the diaphragm after the parasite entered and persisted within the murine myocytes; the mice were infected by intravenous injection of newborn larvae. Gene expression analysis was based on the alignment results. Differentially expressed genes (DEGs) were identified based on their expression levels in various samples, and functional annotation and enrichment analysis were performed. Results The most extensive and dynamic gene expression responses in host diaphragms were observed during early infection (1 dpi). The number of DEGs and genes annotated in the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology databases decreased significantly in the infected mice compared to the uninfected mice at 3 and 7 dpi, suddenly increased sharply at 10 dpi, and then decreased to a lower level at 15 dpi, similar to that observed at 3 and 7 dpi. The massive initial reaction of the murine muscle cells to Trichinella infection steadied in the later stages of infection, with little additional changes detected for the remaining duration of the studied process. Although there were hundreds of DEGs at each time point, only 11 genes were consistently up- or downregulated at all 5 time points. Conclusions The gene expression patterns identified in this study can be employed to characterize the coordinated response of T. spiralis-infected myocytes in a time-resolved manner. This comprehensive dataset presents a distinct and sensitive picture of the interaction between host and parasite during intracellular infection, which can help to elucidate how pathogens evade host defenses and coordinate the biological functions of host cells to survive in the mammalian environment.

The initial reaction mechanism and thermal sensitivity of a fluoropolymer-containing energetic molecular system: the coupling effect of interfacial interactions and free radical reactions

CrystEngComm ◽  
2021 ◽  
Vol 23 (16) ◽  
pp. 3006-3014
Author(s):  
Wen Qian
Keyword(s):  
Free Radical ◽  
Coupling Effect ◽  
Molecular System ◽  
Thermal Sensitivity ◽  
Radical Reactions ◽  
Initial Reaction ◽  
Interfacial Interactions ◽  
Free Radical Reactions ◽  
Molecular Systems ◽  
Reactive Molecular Dynamics

A strategy combining classic and reactive molecular dynamics is applied to find the coupling effect of interfacial interactions and free radical reactions during the initial thermal decomposition of fluoropolymer-containing molecular systems.

scholarly journals Effect of Prior Oxidation on the Reduction Behavior of Magnetite-Based Iron Ore During Hydrogen-Induced Fluidized Bed Reduction

2021 ◽  
Author(s):  
Heng Zheng ◽  
Daniel Spreitzer ◽  
Thomas Wolfinger ◽  
Johannes Schenk ◽  
Runsheng Xu
Keyword(s):  
Fluidized Bed ◽  
Partial Oxidation ◽  
Iron Ore ◽  
Reduction Rate ◽  
Deep Oxidation ◽  
Initial Reaction ◽  
Oxidation Treatment ◽  
Rate Limiting Step ◽  
Rate Limiting ◽  
Prior Oxidation

AbstractMagnetite-based iron ore usually shows a high sticking tendency and a poor reducibility in the fluidized bed because of its dense structure. To enhance the fluidization and reduction behaviors of magnetite-based iron ore during hydrogen-induced fluidized bed reduction, the effect of a prior oxidation treatment is investigated. The results show that the untreated magnetite-based iron ore cannot be fluidized successfully in the tested temperature range between 600 °C and 800 °C. At 600 °C reduction temperature, the de-fluidization can be avoided by a prior oxidation treatment. At higher reduction temperatures, the fluidization behavior can be further improved by an addition of 0.5 wt pct MgO. Magnesiowüstite (FexMg1−xO) is formed, which decreases the contact chance of the sticky surface between particles. Regarding to the reduction rate, a prior partial oxidation is more beneficial compared to deep oxidation. The kinetic analysis shows that MgO could promote the initial reaction. The reaction rate limiting step is no longer diffusion but chemical reaction for prior partly oxidized samples. A prior partial oxidation combined with an addition of MgO is considered to be a promising pretreatment method for a successful processing of magnetite-based iron ore.

scholarly journals Mechanism of the improvement of the energy of host–guest explosives by incorporation of small guest molecules: HNO3 and H2O2 promoted C–N bond cleavage of the ring of ICM-102

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yiwen Xiao ◽  
Lang Chen ◽  
Kun Yang ◽  
Deshen Geng ◽  
Jianying Lu ◽  
...  
Keyword(s):  
Bond Cleavage ◽  
Exothermic Reaction ◽  
High Energy ◽  
Ring Structure ◽  
High Energy Density ◽  
Initial Reaction ◽  
Heating Rates ◽  
Thermal Stabilities ◽  
Guest Molecules ◽  
Molecule Reaction

AbstractHost–guest materials exhibit great potential applications as an insensitive high-energy–density explosive and low characteristic signal solid propellant. To investigate the mechanism of the improvement of the energy of host–guest explosives by guest molecules, ReaxFF-lg reactive molecular dynamics simulations were performed to calculate the thermal decomposition reactions of the host–guest explosives systems ICM-102/HNO3, ICM-102/H2O2, and pure ICM-102 under different constant high temperatures and different heating rates. Incorporation of guest molecules significantly increased the energy level of the host–guest system. However, the initial reaction path of the ICM-102 molecule was not changed by the guest molecules. The guest molecules did not initially participate in the host molecule reaction. After a period of time, the H2O2 and HNO3 guest molecules promoted cleavage of the C–N bond of the ICM-102 ring. Stronger oxidation and higher oxygen content resulted in the guest molecules more obviously accelerating destruction of the ICM-102 ring structure. The guest molecules accelerated the initial endothermic reaction of ICM-102, but they played a more important role in the intermediate exothermic reaction stage: incorporation of guest molecules (HNO3 and H2O2) greatly improved the heat release and exothermic reaction rate. Although the energies of the host–guest systems were clearly improved by incorporation of guest molecules, the guest molecules had little effect on the thermal stabilities of the systems.

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